H. E. Humaid Mohammad Obaid Al Qutami · 2008-10-21 · H. E. Humaid Mohammad Obaid Al Qutami Minister of Health, United Arab Emirates Chairman, Board of Trustees, Sheikh Hamdan Bin

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Scientific research and continuous development of human knowledge are important compo -

nents for promoting modern sciences. In accordance with this concept, the Centre for Arab

Genomic Studies plays an important role in the medical and genomic research activities in the

United Arab Emirates.

This effort is a natural reflection of the wise leadership headed by H.H. Sheikh Khalifa Bin

Zayed Al Nahayan, President of the United Arab Emirates, H.H. Sheikh Mohammad Bin

Rashid Al Maktoum, Vice-President and Prime Minister of the United Arab Emirates and

Ruler of Dubai, and their Highnesses Members of the Supreme Council of Rulers of the

Emirates. In fact, the Centre for Arab Genomic Studies came to existence only following the

prudent vision of H.H. Sheikh Hamdan Bin Rashid Al Maktoum, Deputy Ruler of Dubai and

Minister of Finance and Industry, to establish Sheikh Hamdan Bin Rashid Al Maktoum Award

for Medical Sciences in 1999 with the aim to support and develop medical research in the

country.

The present conference, held for the first time in Dubai, is an important testimony of the sin -

cere efforts exerted by the Centre for Arab Genomic Studies to investigate genetic disorders

available in Arab people and to strengthen mutual Arab cooperation to build a common data -

base of genetic disorders encountered in the region. This is an impressive effort that was soon

recognized by many international bodies including the Human Genome Organisation, which

we proudly welcome in this event.

Despite the recent inception of the Centre for Arab Genomic Studies, its achievements have

been unmatched in the region. I sincerely do wish all the success to the First Pan Arab Human

Genetics Conference.

H. E. Humaid Mohammad Obaid Al Qutami

Minister of Health, United Arab Emirates

Chairman, Board of Trustees,

Sheikh Hamdan Bin Rashid Al Maktoum Award for Medical Sciences

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Congenital disorders are very common in the Arab World and their prevalence is considered

as the highest worldwide. Because of those diseases, many patients suffer and, unfortunately,

the genetic causes of many abnormalities remain unknown. Genetic disorders are usually

related to social measures such as high rates of consanguinity, the trend to have many chil -

dren, and the lack of proper knowledge about inherited disorders.

The direct follow-up of His Highness Sheikh Hamdan Bin Rashid Al Maktoum, Deputy Ruler

of Dubai and Minister of Finance and Industry, of medical activities, resulted in the establish -

ment of his Sheikh Hamdan Bin Rashid Al Maktoum Award for Medical Sciences. He also

paid special attention to launch the activities of the Centre for Arab Genomic Studies to

closely examine genetic disorders occurring in the United Arab Emirates and the rest of the

Arab World.

Since the establishment of the Centre in 2003, it has been able to accomplish most its objec -

tives in the United Arab Emirates by building a database of genetic disorders in the country

that is publicly available through the Centre’s website to all scientists interested in genetic

disorders.

Today, the Centre is aiming to broaden its database by including all diseases occurring in

Arab individuals and by building a strong link to all centers and scientists interested in human

genetics in the region. For that target the Centre for Arab Genomic Studies recently formed

its Arab Council which includes eminent Arab scientists working on human genetics.

We are happy to welcome our guests from the Human Genome Organisation, who are attend -

ing the First Pan Arab Human Genetics Conference. It is our aim to build strong relations

with international organizations in order to initiate exchange of information between the Arab

World and international organizations.

We are confident that the standards of the conference will be very high since distinguished sci -

entists from the Arab World and from International institutes will participate in the scientific

program.

I wish you all the best and a happy visit to Dubai.

Prof. Najib Al Khaja

General Secretary,

Sheikh Hamdan Bin Rashid Al Maktoum Award for Medical Sciences

President, Centre for Arab Genomic Studies

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One of the roles of the Human Genome Organisation (HUGO) is to encourage and promote

international collaboration and co-operation. The global members of the scientific communi -

ty are natural collaborators and we are at our most productive when we share our thinking.

This is not only achieved by collaborations that cross academic boundaries into medicine,

genetics and biochemistry but also collaborations on the personal level. The rewards and ben -

efits of the results from the increasing knowledge generated by the human genome project

must be made available to all and not retained for the wealthy nations only. The massive

amount of new genome-wide information that is now being generated will underpin research

on human biology and disease in this century and beyond. Geneticists worldwide are facing a

tremendous challenge to wisely read and use this information. This information must be trans -

lated into knowledge and understanding of biology and better actions to alleviate, treat and

eventually to cure. These are exciting times for genome science and it is no longer a margin -

al field of biology, but offers a real opportunity to contribute to the betterment of mankind.

HUGO's Council is also committed to the encouragement of this science to the next genera -

tion. These young researchers need to be supported and given the tools to do world-class sci -

ence. It is in the interest of all that the best minds are encouraged to generate new knowledge

and new technologies. HUGO also is committed to promoting a greater understanding to the

wider lay audience.

As President of HUGO I have great pleasure in sending my best wishes to all the delegates at

this 1st Pan Arab Human Genetics Conference who represent so many countries in the region

and hope that this conference will be the first of many successful events.

Prof. Leena Peltonen-Palotie

President, Human Genome Organisation

Academy Professor, University of Helsinki, Helsinki, Finland

The Broad Institute, Boston, MA, USA

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Dr. Mahmoud Taleb Al Ali

Director, Centre for Arab Genomic Studies

Chairperson, Scientific Committee of the

First Pan Arab Human Genetics Conference

The Centre for Arab Genomic Studies is pleased to welcome you all to the 1st Pan Arab

Human Genetics Conference (April 4-6, 2006) in Dubai, United Arab Emirates.

Human capital constitutes the most critical element of the health system and forms the basis

for the realization of national health goals in any country. In the Arab world, human genetic

disorders and congenital abnormalities continue to challenge all progress achieved in recent

decades in health care systems. In fact, close to 950 congenital abnormalities and genetic dis -

orders do occur in Arab populations and are responsible for large numbers of perinatal and

neonatal mortalities.

The completion of the Human Genome Project marked the start of the exciting era of genom -

ic applications in medicine and health to recognize and treat human disease at its genetic

roots. Accordingly, this conference is organized to provide a platform for dialogue and edu -

cation on issues related to human genetics and to bring together Arab and international

experts to set the priorities for research on genetic disorders in the region. In this regard, we

do warmly thank the Human Genome Organisation (HUGO) for its active participation and

support to the conference. We also feel very proud that the first step of HUGO towards the

Arab world is being achieved through the Centre for Arab Genomic Studies.

During the conference, the Centre for Arab Genomic Studies welcomes for the first time mem -

bers of the recently formed Council of CAGS representing a number of Arab countries. The

Council of CAGS was formed with the aims to facilitate the exchange of information on genet -

ic disorders occurring in Arab countries and to orchestrate data collection from the region

similar to the effort CAGS achieved in the United Arab Emirates. The current, and prelimi -

nary, Council of CAGS includes a number of regional scientists from Bahrain, Egypt, Jordan,

Kuwait, Lebanon, Oman, Qatar, Saudi Arabia, Sudan, and Tunisia. In the future, CAGS will

extend memberships to a larger group of scientists and include other Arab countries accord -

ing to a stepwise model in accordance to the expanding activities of CAGS.

I welcome you all in the lively city of Dubai and wish success to all participants in the

conference.

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SHEIKH HAMDAN BIN RASHID AL MAKTOUM AWARD FOR MEDICAL SCIENCES

Sheikh Hamdan Bin Rashid Al Maktoum Award for Medical Sciences was established in 1999 under

the patronage of H.H. Sheikh Hamdan Bin Rashid Al Maktoum, Deputy Ruler of Dubai and Minister

of Finance and Industry with the objective of honoring scientists from every part of the world who

tirelessly pursue distinctive medical research that serves the larger interests of humanity.

The initial focus of the foundation was on two major categories of awards, the International and

National categories. In the international category, there were three sections, the Grand Hamdan

Award, three Research Excellence Awards and four awards for volunteers in humanitarian medical

services. In subsequent years, an additional category of the Arab World Award was introduced fol-

lowed by an additional award to the UAE category - an award for the clinical department in the pub-

lic sector. Today, the foundation’s emphasis is on supporting and encouraging scientific research in

the UAE with the provision of research grants. This activity has already yielded excellent results with

publications in reputable journals.

The last three award terms proved to be widely successful as recognized by international observers

and testified to by leading researchers vying for the award. This success reflects on the foundation’s

international reputation and its high scientific credibility and level of performance.

Another milestone in the history of the foundation was the opening of a centre for genetic research

as a part of the research support in the United Arab Emirates. The Centre for Arab Genomic Studies

was established in the year 2003. The vision of H.H. Sheikh Hamdan Bin Rashid Al Maktoum to alle-

viate human suffering from genetic diseases in the Arab World crystallized in the establishment of

the Centre to characterize and prevent genetic disorders and transfigure the future practice of health

care in the region. The priority objectives of the Centre for Arab Genomic Studies are to educate

the public and professionals alike on the important impact of genetic diseases in the Arab World and

the methods and benefits of early genetic diagnosis. A local committee of scientists has been estab-

lished to create an initial genetic diseases database and to prepare a two level scientific study the

objective of which is first, to create a local database in which locally prevalent genetic diseases are

registered, and then to incorporate data on genetic diseases from other Arab countries.

The foundation is now in the fourth term of awards and besides enriching scientific research, it has

an additional objective of enhancing the nature of scientific interaction between doctors in this coun-

try and the overseas medical centers.

The Fourth Award Ceremony and the Dubai International Conference for Medical Sciences will be

held in Dubai from 18 -21 December, 2006. We invite you to participate in this seminal event.

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CENTRE FOR ARAB GENOMIC STUDIES

Genetic and congenital disorders are responsible for a considerable proportion of perinatal and

neonatal mortalities in Arab populations. At present, congenital malformations are the second lead-

ing cause of infant mortality in countries of the Gulf Cooperation Council (GCC), including Bahrain,

Kuwait, Oman, and Qatar.

In the United Arab Emirates (UAE), the significant changes in the health system, including enhanced

and advanced genetic services, have revealed that a high frequency of genetic disorders exist in the

country, particularly autosomal recessive traits.

The vision of H.H. Sheikh Hamdan Bin Rashid Al Maktoum to alleviate human suffering from genet-

ic diseases in the Arab World crystallized in the establishment of the Centre for Arab Genomic

Studies (CAGS) on 25th June 2003 to characterize and prevent genetic disorders and transfigure

the future practice of health care in the region. Some of the priority objectives of the Centre for Arab

Genomic Studies are to educate the public and professionals alike on the important impact of genet-

ic diseases in the Arab World and the methods and benefits of early genetic diagnosis. The Centre

for Arab Genomic Studies also plans to provide comprehensive genetic services by translating

research achievements into well-integrated patient treatment programs. Concurrently, it will also

address the ethical, legal, and social issues that may arise with the implementation of such pro-

grams.

The Centre for Arab Genomic Studies includes two scientific committees: The Executive Board of

CAGS is composed of a number of local scientists and it represents the governing body and the

legal trustee of all activities of the centre. The Council of CAGS includes a number of regional sci-

entists and it facilitates the exchange of information on genetic disorders occurring in Arab countries.

Countries represented in the Council of CAGS currently include: Bahrain, Egypt, Jordan, Kuwait,

Lebanon, Oman, Qatar, Saudi Arabia, Sudan, and Tunisia. In the future, CAGS aims to extend

memberships to a larger group of scientists and include other Arab countries.

In 2004, the Centre for Arab Genomic Studies initiated a pilot project to establish the “Catalogue of

Transmission Genetics in Arabs” (CTGA) database of genetic disorders in Arabs

(www.cags.org.ae). CAGS coordinated the collection of data on genetic disorders in the UAE pop-

ulation as a model system to be implemented in other Arab countries in the future. The sources of

information included nationally- and internationally-published literature as well as local laboratory

records.

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At present, CTGA hosts entries for approximately 1000 phenotypes and related genes described in

Arab individuals. Of these, about 250 phenotypic descriptions and related genes were observed in

the Arab population of the UAE. The wealth of information that CTGA database is accumulating is

an indispensable tool for scientists to recognize Arab colleagues working in similar domains and to

decide on possible collaborations or exchange of knowledge.

Currently, the priority of CTGA is to provide timely information on the occurrence of genetic disor-

ders in Arab individuals. It is anticipated that data from Arab countries other than the UAE will be

exhaustively searched and incorporated in CTGA.

In order to play a positive role among international scientific societies, CAGS aims at publishing its

results in international and regional peer-reviewed journals. The first technical report on the struc-

ture and characteristics of the CTGA database were published in January 2006 in the special

Database Issue by the eminent journal Nucleic Acids Research. In the future, CAGS will contribute

to a series of articles highlighting the continuously growing content of the CTGA database as it

expands and covers new populations.

Following the recent completion of the project to unravel the DNA sequence of the human genome,

focus in the Centre for Arab Genomic Studies is to conduct functional genomic studies. These

include large-scale or global investigations of gene function and dissection of complex regulatory

pathways. The presence of many genetic disorders in the region with unknown molecular patholo-

gies offers an excellent opportunity for local researchers to contribute to this global effort. A large

number of genetic disorders in the Arab World are only confined to local family structures and were

not described elsewhere in the world. The study of the genetic pathologies leading to these disor-

ders will help us to understand the functions of the associated genes in health and disease states

as well as pave the way to design specific prevention and treatment programs for each of these dis-

orders.

Although the extended consanguineous family structures, commonly present in Arab societies, lead

to the propensity of severe congenital inherited diseases in the country, they also tend to display

peculiar distribution patterns for those disorders not present in many other world populations. A

major model that explains this concept is the vertical dissemination of a genetic mutation in an Arab

family, where mutation carriers mostly remain concentrated within the extended family; thus, offer-

ing great opportunities to depict the genetic nature of their disease predisposition. In fact, the Centre

for Arab Genomic Studies offers an important opportunity to develop such a strategy since it initiat-

ed links to global centers with a room for further development of partnerships within the Arab World

and at international platforms.

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HUMAN GENOME ORGANISATION

The Human Genome Organisation (HUGO) is the international organization of scientists involved in

human genetics. Established in 1989 by a collection of the world’s leading human geneticists, the

primary ethos of the Human Genome Organisation is to promote and sustain international collabo-

ration in the field of human genetics.

The Human Genome Organisation (HUGO) was conceived in late April 1988, at the first meeting on

genome mapping and sequencing at Cold Spring Harbor. HUGO emerged from the human chromo-

some meetings that took place during the1970’s and 1980’s. For some time, as the genome initia-

tives got under way in individual nations, the need for an international coordinating scientific body

had been under discussion. The idea of HUGO was particularly Sydney Brenner’s. He also suggest-

ed the name of the organization and its acronym.

At a rump session called to discuss the proposal at Cold Spring Harbor on April 30, 1988, Victor

McKusick (Baltimore) was asked to serve as founding president. A Founding Council was assem-

bled from among those at the Cold Spring Harbor meeting, supplemented by others, to a total of 42

scientists from 17 countries. The initial membership included many of the individuals who went on

to lead the human genome project through to its completion.

HUGO’s Mission Statement

This mission statement is based on the principles laid down in HUGO’s aims and objectives:

• to investigate the nature, structure, function and interaction of the genes, genomic elements and

genomes of humans and relevant pathogenic and model organisms;

• to characterize the nature, distribution and evolution of genetic variation in humans and other rel-

evant organisms;

• to study the relationship between genetic variation and the environment in the origins and char-

acteristics of human populations and the causes, diagnoses, treatments and prevention of dis-

ease;

• to foster the interaction, coordination, and dissemination of information and technology between

investigators and the global society in genomics, proteomics, bioinformatics, systems biology,

and the clinical sciences by promoting quality education, comprehensive communication, and

accurate, comprehensive, and accessible knowledge resources for genes, genomes and dis-

ease;

• to sponsor factually-grounded dialogues on the social, legal, and ethical issues related to genet-

ic and genomic information and championing the regionally-appropriate, ethical utilization of this

information for the good of the individual and the society.

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HUGO has, over the years, played an essential role behind the scenes of the human genome proj-

ect. With its mission to promote international collaborative effort to study the human genome and

the myriad issues raised by knowledge of the genome, HUGO has had noteworthy successes in

some of the less glamorous ñ but nonetheless vital ñ aspects of the human genome project.

HUGO’s Gene Nomenclature Committee is part of the important task of establishing a common lan-

guage for the human genome, and many journals will not publish a paper until any new human gene

symbols have been approved by the committee. Also, the Human Genome Variation Committee,

which has now evolved into the Human Genome Variation Society, has been coordinating efforts to

assess genetic variation. HUGO’s Ethics Committee has produced policy statement on issues from

EST patents to cloning and benefit sharing for research participants. These statements have had

important effects on policy within the European Union.

HUGO’s annual meeting reflects the international nature of the organization, with the last five meet-

ings being held in Japan, Berlin, Cancun, Shanghai and Edinburgh. These meetings provide the

only occasion for the international human genome community to meet and they also provide an

opportunity for the host nation to draw local attention to genomic science. In addition to genomic

and genetic science, these meetings include sessions on ethical, legal and social issues. This pro-

vides and excellent, and rare, opportunity for the scientists and bioethicists to meet.

A truly international organization, HUGO has been instrumental in reaching out to groups and

nations that have not actively participated in the human genome project. Following a call to the

members HUGO has succeeded in recruiting scientists from 24 countries to act as ambassadors for

the genome community. These individuals will do outreach work in conveying the knowledge and

implications of the human genome project to teachers, social workers and educational ministries -

the ‘first line’ of society who must be informed and ready for the changes that knowledge of the

genome will bring.

Maximizing the benefits of the human genome project for all humanity, and not just the wealthy

nations, requires international collaboration, resource sharing and continued dialogue. HUGO

through its international membership and ethos is in a unique position to promote that vision. HUGO

is constantly looking for new means of enabling international co-operation and building on the infra-

structure that it already has in place.

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GENERAL SECRETARIAT OF THESHEIKH HAMDAN AWARD FOR MEDICAL SCIENCES

Prof. Najib Al KhajaSecretary General

Dr. Mona Al RukhaimiDeputy Secretary General

Dr. Ahmed Al HashemiChairman, Finance Committee

Prof. Yousef M. AbdulrazzaqChairman, Scientific Committee

Mr. Abdullah Bin SouqatChairman, Conference Committee

Dr. Hussain Nasser Al RahmaRapporteur

Dr. Ahmed Al JaziriMember

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EXECUTIVE BOARD OF THECENTRE FOR ARAB GENOMIC STUDIES

Prof. Najib Al KhajaSecretary General, Sheikh Hamdan Bin Rashid Al Maktoum Award for Medical Sciences


Dr. Mahmoud Taleb Al AliDirector, Centre for Arab Genomic Studies

Asst. Prof. Ghazi Omar TadmouriAssistant Director, Centre for Arab Genomic Studies

Dr. Erol BaysalConsultant Molecular Geneticist, Head of Molecular Genetics, Dubai Genetics and Thalassemia Center, Al-Wasl Hospital,

Department of Health and Medical Services, Dubai

Prof. Lihadh Al-GazaliProfessor, Department of Pediatrics, Faculty of Medicine and Health Sciences, UAE University, Al-Ain

Asst. Prof. Ahmed H. Al-MarzouqiAssistant Professor, Department of Biochemistry, Faculty of Medicine and Health Sciences, UAE University, Al-Ain

Dr. Mohammed NaveedSpecialist Clinical Geneticist, Centre for Arab Genomic Studies, Dubai

Dr. Najat RashidDirector, Directorate of Medical Laboratories, Ministry of Health, UAE

Assoc. Prof. Tahir A. RizviAssociate Professor, Department of Medical Microbiology, Faculty of Medicine and Health Sciences, UAE University, Al-Ain

Dr. Mouza Al-SharhanConsultant & Head of Department of Histopathology, Dubai Hospital, Department of Health and Medical Services, Dubai

Prof. Taher El-SharkawyProfessor, Department of Physiology, Faculty of Medicine and Health Sciences, UAE University, Al-Ain

Dr. Mansour Al ZarouniDirector of Laboratory Section, Al-Qassimi and Kuwaiti Hospitals, Sharjah Medical Area, Ministry of Health, Sharjah

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ARAB COUNCIL OF THE CENTRE FOR ARAB GENOMIC STUDIES

Prof. Adekunle D. AdekileDepartment of Pediatrics, Faculty of Medicine, Kuwait University, Kuwait

Dr. Aida I. Al AqeelInborn Errors of Metabolism, Endocrinology and Genetics, Department of Pediatrics, Armed Forces Hospital, Saudi Arabia

Dr. Shaikha Al ArrayedGenetics Unit, Salmaniya Medical Complex, Ministry of Health, Bahrain

Prof. Riad A. BayoumiDepartment of Biochemistry, College of Medicine, Sultan Qaboos University, Oman

Prof. Habiba ChaabouniLaboratory of Human Genetics, Faculty of Medicine of Tunis, Service of Hereditary Disorders,

Hospital Charles Nicolle, Tunisia

Prof Lotfi ChouchaneLaboratory of Immuno-Oncology, Faculty of Medicine of Monastir, Tunisia

Weill Cornell Medical College, Qatar

Prof. Hanan HamamyNational Center for Diabetes Endocrinology and Genetics, Amman, Jordan

Prof. Andre MegarbaneUnit of Medical Genetics, Laboratory of Molecular Biology & Cytogenetics, Faculty of Medicine,

University Saint-Joseph, Lebanon

Prof. Rabah M. ShawkySociety of Human Genetics, Medical Genetics Center, Faculty of Medicine, Ain-Shams University, Egypt

Prof. Laila ZahedCytogenetics Laboratory, Department of Pathology & Laboratory Medicine,

American University of Beirut Medical Center, Lebanon

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SCIENTIFIC COMMITTEE

Dr. Mahmoud Taleb Al Ali (Chairperson)

Dr. Ghazi Omar Tadmouri (Vice-Chairperson)

Prof. Lihadh Al-Gazali

Prof. Taher Y. El Sharkawy

Dr. Ahmed Al-Marzouqi

Dr. Erol Baysal

Dr. Mansoor Al-Zarouni

Dr. Mohammed Naveed

Dr. Mouza Al-Sharhan

Dr. Najat Rashid

Dr. Nisrine Bissar-Tadmouri

Dr. Tahir A. Rizvi

ORGANIZING COMMITTEE

Prof. Najib Al Khaja (President)

Dr. Mahmoud Taleb Al Ali (Vice-President)


Dr. Ahmed Al-Marzouqi

Dr. Erol Baysal

Dr. Ghazi Omar Tadmouri

Dr. Mansoor Al-Zarouni

Dr. Mohammed Naveed

Dr. Mouza Al-Sharhan

Dr. Najat Rashid

Dr. Tahir A. Rizvi

Mr. Najam Ali Mirza

Mrs. Sarah Al Haj Ali

Mr. Barraq A. Istaityyah

Mr. Sujathan R. Nair

Mrs. Nourhan Badawy

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The Department of Health and Medical Services (DOHMS) and the Centre for Arab Genomic

Studies (CAGS), a division of Sheikh Hamdan Award for Medical Sciences, are pleased to

announce the international workshop on “Fundamental Approaches in the Molecular Diagnosis of

Hemoglobinopathies” in association with the Department of Health and Medical Services

(DOHMS), Dubai.

The workshop will be held on 4th April, 2006, at the Genetic and Thalassemia Center, Al Wasl

Hospital, Dubai, United Arab Emirates.

Objectives

• To help participants acquire and enhance their laboratory skills in using the latest DNA diag-

nostic techniques offered for a wide spectrum of hemoglobin disorders.

• To update knowledge in molecular aspects of hemoglobinopathies.

General Information

The course will be conducted by experts who have extensive experience in the field of molecular

detection of hemoglobinopathies.

Basic DNA detection techniques including PCR, RFLP, restriction enzyme digestion, DNA finger-

printing and automated DNA sequencing will be demonstrated.

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Laboratory Workshop Program

Opening

8.00 - 8.10: Dr. Mahmoud Taleb Al Ali

Consultant & Head of Genetics Department, Genetics & Thalassemia Center, Dubai, UAE

8.10 - 8.20: Dr. Erol Baysal

Consultant Molecular Biology, Head of Molecular Genetics Unit, Genetics & Thalassemia Center, Dubai, UAE

Orientation

• 8.20 - 8.30: Introduction to Molecular Genetics Laboratory

• 8.30 - 9.00: Break

• 9.00 - 11.00: PCR technology and its application in molecular diagnosis

• 12.00 - 13.00: Reverse dot -blot hybridization

• 14.00 - 17.00: Genome analysis in various monogenic disorders

Manual and automated DNA sequencing

Interpretation of results

Workshop Seminars

• Introduction to DNA: The basis of molecular medicine

• Methods and techniques in molecular biology

• Molecular characterization of hemoglobinopathies

• Seminars will be scheduled during the course of the laboratory workshop.

Closing Remarks


Dr. Erol Baysal

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WEDNESDAY, APRIL 5, 2006

08.00 - 10.00

Conference Registration

10.00 - 10.10

H.E. Humaid Mohammad Obaid Al Qutami

Minister of Health, UAE

Chairman, Sheikh Hamdan Bin Rashid Al Maktoum Award for Medical Sciences

10.10 - 10.20

Prof. Najib Al Khaja


10.20 - 10.30

Prof. Hans-Hilger Ropers

Member, Human Genome Organisation (HUGO) Council

10.30 - 10.40


Director, Centre for Arab Genomic Studies

10.40 - 11.00

Coffee Break

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The First Pan Arab Human Genetics Conference is accredited by the Faculty of Medicine and Health

Sciences, UAE University, to provide continuing medical education to delegates.

Each session is allocated a certain number of CME hours. Attending all sessions of the conference

will grant the attendee a total of 11.15 CME hours.

Delegates will be provided with a set of 'attendance forms'. The delegate must complete the atten-

dance forms by filling in the special code given out at each session. These forms must be complet-

ed and handed in at the end of each session. Credits will not be given if the code has not been

included.

Accredited by Faculty of Medicine and Health Sciences, UAE University

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Session 1:

Population Genetics - Genetic Disorders in the Arab World

Chairpersons: Prof. Ahmed Mandil and Prof. Taher Y. El Sharkawy

11.00 - 11.15

An Overview of the Human Genome Organisation

Prof. Sue Povey

Chairperson, The HUGO Gene Nomenclature Committee

Department of Biology, University College London, UK

11.15 - 11.45

Genetic Disorders in Arabs: CAGS Approach


Centre for Arab Genomic Studies, Dubai, UAE

11.45 - 12.15

Genetic Disorders in United Arab Emirates


Department of Pediatrics, UAE University, UAE

12.15 - 12.45

Genetic Diseases in Lebanon

Prof. André Mégarbané

Unit of Medical Genetics, University Saint-Joseph, Lebanon

12.45 - 13.15

Genetic Diseases in Bahrain: An Overview

Dr. Shaikha S. Al Arrayed

Salmaniya Medical Complex, Ministry of Health, Bahrain

13.15 - 14.00

Meeting the Press

14.00 - 15.00

Lunch

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Session 2:

Clinical and Molecular Genetics of Human Disease

Chairpersons: Dr. Tahir A. Rizvi and Dr. David Wilson

15.00 - 15.30

Genetics of Mental Retardation


Member, HUGO Council

Director, Max-Planck Institute for Molecular Genetics, Berlin, Germany

15.30 - 16.00

An Overview of the Genetics of Mental Retardation in Tunisia

Prof. Habiba Bouhamed-Chaabouni


16.00 - 16.30

Coffee Break

16.30 - 17.00

Autosomal Recessive Primary Microcephaly

Prof. Geoff Woods

Department of Genetics, Cambridge University, UK

17.00 - 17.30

A Clinical Approach to the Dysmorphic Child

Prof. Rabah Mohamed Shawky

Society of Human Genetics, Ain-Shams University, Egypt

17.30 - 18.00

Ectrodactyly with Aplasia of Long Bones (OMIM 119100) in a Large Inbred Arab Family with

an Apparent Autosomal Dominant Inheritance and Reduced Penetrance: Clinical and

Genetic Analysis

Dr. Mohammed Naveed

Centre for Arab Genomic Studies, UAE

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10.30 - 11.00

Molecular Diagnosis of Chronic Myeloid

Leukemia

Prof. Riad A. Bayoumi

Sultan Qaboos University, Muscat, Oman

11.00 - 11.30

Coffee Break

11.30 - 12.00

Hemoglobin Disorders in the United Arab

Emirates

Dr. Erol A. Baysal

Genetics and Thalassemia Center,

Al-Wasl Hospital, UAE

12.00 - 12.30

Clinical Implications of the Arab s - Globin

Gene Haplotype

Prof. Adekunle D. Adekile

Department of Pediatrics, Kuwait University,

Kuwait

12.30 - 13.00

Genetics of Familial Mediterranean Fever



13.00 - 14.00

Lunch

THURSDAY, APRIL 6, 2006

Session 3:

Genomics, Cancer Genetics, and

Genetics of Blood Disorders

Chairpersons: Dr. Ahmed H. Al-Marzouqi

and Dr. Mouza Al-Sharhan

09.00 - 09.30

Genomic Landscape behind Common

Traits of Medical Importance in Eurasia

Prof. Nick K. Yankovsky

Chairperson, The HUGO Education

Committee

Head, Genome Analysis Laboratory,

Institute of General Genetics,

Russian Academy of Science, Russia

09.30 - 10.00

DNA Methylation: Involvement in

Human Disease

Dr. Osman El-Maarri

University of Bonn, Germany

10.00 - 10.30

The Genetics of Breast Cancer: From

Biology to Clinical Applications

Prof. Lotfi Chouchane

Faculty of Medicine of Monastir, Tunisia,


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THURSDAY, APRIL 6, 2006

Session 4:

Cytogenetics, Consanguinity, and

Bioethics

Chairpersons: Dr. Hans Meijer

and Dr. Kamal A. Khazanehdari

14.00 - 14.30

Progress towards the Understanding

and Treatment of Tuberous sclerosis

Prof. Sue Povey

Chairperson, The HUGO Gene

Nomenclature Committee Department of

Biology, University College London, UK

14.30 - 15.00

Cytogenetics Services, Quality

Management and Challenges

Prof. Laila Zahed

American University of Beirut Medical

Center, Lebanon

15.00 - 15.30

New Challenges for Neuromuscular

Diseases in the Middle East

Prof. Jon Andoni Urtizberea

Research Director, European

Neuromuscular Center, The Netherlands

15.30 - 16.00

Coffee Break

16.00 - 16.30

Consanguineous Marriages in the Arab World

Prof. Hanan Hamamy

National Center for Diabetes,

Endocrinology & Genetics, Jordan

16.30 - 17.00

Interest of Consanguineous Families in the

Understanding of Genetic Disorders:

Lebanese Cases

Prof. André Mégarbané

Unit of Medical Genetics,

University Saint-Joseph, Lebanon

17.00 - 17.30

Islamic Perspective on Human Cloning, Stem

Cell Research

and Pre-implantation Genetic Diagnosis (PGD)

Dr. Aida Ibrahim M. Al Aqeel

Armed Forces Hospital, Saudi Arabia

17.30 - 18.00

Recommendations / Closing Ceremony

31

32

In 1964, Prof. Sue Povey received a BA in Natural Sciences (genetics) at Cambridge. After clinical studies at UCH

she qualified in medicine in 1967 and went on to work for the Save the Children Fund in Algeria. In 1970 she

returned to take up a scientific post in MRC Human Genetics at University College London (UCL) where she

worked until 2000. She is now Haldane Professor of Genetics at UCL. Her long term interests are in identification

of human genes, building of genetic maps and in the disease Tuberous Sclerosis, however her main effort now is

in gene nomenclature where she is chair of the HUGO Gene Nomenclature Committee.

An Overview of the Human Genome Organisation

Sue Povey

The HUGO Gene Nomenclature Committee, Human Genome Organisation, UK

The original idea of HUGO, the Human Genome Organisation, was proposed by Sydney Brenner at the first

Genome Mapping and Sequencing meeting at Cold Spring Harbor, USA, in April 1988 and realized in September

of that year with Dr. Victor McKusick as its first President. McKusick was already known throughout clinical genet-

ics as the originator of the authoritative “Mendelian Inheritance in Man”, now OMIM. Since the beginning, HUGO

has been an international organization with an emphasis on co-ordination of scientific efforts and dissemination of

genomic data to all, and with consideration of the ethical and legal implementations of such knowledge in differ-

ent countries and cultures. The annual major HGM meetings have introduced the latest work in Genome science

to young investigators in many different countries and the statements of the Ethical Committee have influenced

many policy decisions. The HUGO Gene Nomenclature Committee (HGNC), chaired by myself since 1997, grew

out of a committee on Gene Nomenclature that was established in 1979 and led by Tom Shows and Phyllis

McAlpine. This was a major feature of the Human Gene Mapping Workshops, meetings held between 1970 and

1991 where those individuals interested in human gene mapping attempted to correlate all known facts and pro-

duce a summary of the latest state of every human chromosome. They recognized that a standardized gene name

is needed whenever a person wants to communicate information to another person about a gene. The HGNC has

the goal that every human gene will have a unique and universally used name and an acronym (symbol) and will

be defined by associated data, usually consisting of a reference nucleotide sequence. Collaboration with the

Mouse Genomic Nomenclature Committee means that equivalent genes in the two species nearly always have the

same name. In March 2006, the HGNC database (http://www.gene.ucl.ac.uk/nomenclature/) contains nearly

23,000 approved symbols and names. An important future task for HUGO will be to encourage the enthusiasm

and knowledge of young scientists particularly in those countries where resources are severely limited, and to help

them to use their skills in the best practical way. A significant part of the future role of HUGO may be to increase

awareness of the range of different ethical dilemmas in different regions of the world posed by the rapid advances

in genetic technology. Overall, the goal will be to bring more countries and more scientists into the global network

of human genetics and genomics.

Session 1: Population Genetics - Genetic Disorders in the Arab World (11.00 - 11.15)

Prof. Sue Povey

33

Dr. Ghazi Omar Tadmouri is assistant director of the Centre for Arab Genomic Studies (Dubai, United Arab

Emirates). He is also member of the consultancy group supporting the UNDP - Lebanon ”Transfer of Knowledge

Through Expatriate Nationals” (TOKTEN) Project. In years 2000-2004, he was Assistant Professor of Molecular

Biology and Genetics at Fatih University (Istanbul, Turkey). In 1999, he received the degree of Doctor of

Philosophy in Molecular Biology and Genetics from Bogazici University (Istanbul, Turkey). Dr. Tadmouri is author

of more than 20 books and articles in international scientific journals including Lancet, Nucleic Acids Research,

American Journal of Hematology, Human Biology, and others. Since 1994, he presented scientific papers in more

than 40 international conferences and meetings in the USA, Turkey, Lebanon, France, Germany, Spain, Canada,

Malta, Greece, Australia, Sweden, Tunisia, Portugal, Switzerland, the United Arab Emirates, and Kingdom of

Saudi Arabia. He is Member of the Editorial Board of the Saudi Medical Journal and scientific referee for a num-

ber of national and international biomedical journals.

Genetic Disorders in Arabs: CAGS Approach

Ghazi Omar Tadmouri

Centre for Arab Genomic Studies, P.O. Box 22252 Dubai, United Arab Emirates

Genetic and congenital disorders are responsible for a considerable proportion of infant mortalities in Arab popu-

lations. In 2004, the Centre for Arab Genomic Studies (CAGS) launched a project to catalogue genetic disorders

described in Arab populations. The strategy involved the detailed analysis of the United Arab Emirates as a model

by performing extensive search in published research and mining of hospital records. In total, there are not less

than 222 genetic disorders in the Arab population of the United Arab Emirates. This figure may still increase as

CAGS is continuously receiving new data from a variety of sources. Data on genetic disorders in the United Arab

Emirates are publicly accessible through the CTGA database (Catalogue of Transmission Genetics in Arabs) at

www.cags.org.ae. At present, CTGA includes data about 222 phenotypic descriptions and 27 related genes

described in Arab individuals from the UAE. Congenital malformations, deformations, and chromosomal abnor-

malities make up about 50% of these genetic disorders. Endocrine, nutritional, metabolic diseases, neoplasms,

and diseases of the blood and the immune mechanism altogether correspond to approximately 31% of all genet-

ic disorders in the UAE. Although focus is currently aimed at the situation in the UAE, data for other Arab coun-

tries are also searched and incorporated in CTGA. Nowadays, CTGA includes data about a total of 688 pheno-

typic descriptions and 259 related genes in 21 Arab countries. In addition to the United Arab Emirates, most of

these inherited characters occur in subjects from Saudi Arabia, Tunisia, Lebanon, Morocco, and Palestine. The

recent formation of the CAGS Council that includes 12 renowned human geneticists representing Bahrain, Egypt,

Kuwait, Jordan, Lebanon, Oman, Qatar, Saudi Arabia, and Tunisia will help in orchestrating data collection at a

regional scale. In this occasion, we hail all geneticists working on genetics disorders in Arabs to contribute to the

continuous growth of CTGA.



34

Lihadh Al-Gazali is a Professor of Clinical Genetics and Pediatrics in the Faculty of Medicine and Health Sciences,

UAE University. She received her training in genetics in Edinburgh and Leeds, UK. Her research interest is in the

fields of dysmorphology and recessive disorders particularly in Arab populations. She is the author or co-author of

more than 130 peer-reviewed publications.

Genetic Disorders in United Arab Emirates

Lihadh I. Al-Gazali

Department of Paediatrics, Faculty of Medicine and Health Sciences, UAE University,

P.O. Box 17666, Al Ain, UAE

The UAE society is cosmopolitan but the indigenous inhabitants are traditional with puritanical values despite their

exposure to other vastly different cultures and habits. Marriages between consanguineous couples are still the

norm rather than the exception. As a result there is a high frequency of genetic disorders particularly autosomal

recessive types. Despite the high frequency of genetic disorders like hemoglobinopathies and others characteris-

tically found in this population, genetic services are inadequate. Screening for certain disorders like thalassemia

are not applied on a wide scale. Abortion is illegal and therefore prenatal diagnosis or preconception tests are not

done. With the absence of a good national database, deficiency of genetic services and absence of preventative

alternatives for carrier couples, genetic counselors find it difficult to advice pragmatic solutions to issues relating

to genetic diseases. This paper reviews common genetic problems in the UAE with special emphasis on available

genetic services and support to families with children with inherited disorders. Existing barriers to the improve-

ment of clinical services by prenatal counseling are also discussed.



35

He is associate professor of medical genetics and head of the Medical Genetic Unit, St Joseph University,

Lebanon. Dr. Megarbane is author and co-author of more than 130 publications. He is member of the Bioethics

Committee of the Lebanese Order of Physicians, member of the French Society of Genetics and Genetic

Counseling, the American Society of Human Genetics, and the European Society of Human Genetics. Dr.

Megarbane is member of the editorial board of the European Journal of Medical Genetics and member of the

Rammal Rammal Prize committee. He is recipient of four scientific awards, namely: Abdel Hamid Shuman award;

Rammal Rammal Medal, Mohammad El-Fasi young researcher, and Makhzoumi Association award. Dr.

Megarbane has an active research with interest in the domains of mental retardations, dysmorphology, osseous

malformations, and others.

Genetic Diseases in Lebanon

Andre Megarbane, Salim M. Adib

St Joseph University, Beirut, Lebanon

The Lebanese population is composed of a variety of ethnic and sociological communities. This heterogeneity is

the consequence of the situation of Lebanon as a crossroads between Asia, Africa, and Europe. In part due to that

mosaic of different ethnic origins, and to the relatively high, though decreasing, rate of consanguineous marriages,

Lebanon has a high incidence of common and rare genetic diseases. A rapid search of the On-line Mendelian

Inheritance in Men (OMIM) under “Lebanese” elicits several publications on at least 80 abnormalities (OMIM,

2004). Recent studies have suggested that about 2.7% of 29,000 live births in Lebanon in 1999-2002 may have a

genetic defect leading to disease directly detectable at birth (NCPNN, 2004). An additional proportion will be

revealed later in life. Serial screening of about 100,000 newborns in 1995-2004 indicated that common genetic

deficiencies are: G6PD-deficiency (5.2 per 1000; 1 per 100 in boys), congenital hypothyroidism (0.6 per 1000),

phenylketonuria (9 per 100,000) and galactosemia (3 per 100,000). However, the most common genetic condi-

tions remain the Familial Mediterranean Fever and the beta-thalassemia. Available epidemiological information on

genetic diseases in Lebanon will be further detailed in the presentation, in addition to rare diseases.


Dr. Andre Megarbane

36

Dr. Shaikha S. Al Arrayed is the Head of the Genetics Department at Salmaniya Medical Complex and Head of National

committee for the control of hereditary diseases in the Ministry of Health Bahrain since 1993. She graduated as physi-

cian from Cairo University and obtained her Master degree in Human and Clinical Genetics from London University

(1984) and Ph.D. in Genetics from Aberdeen University, Scotland, United Kingdom (1993). Since 2002, Dr. Al Arrayed

is member of the WHO Expert Advisory Panel on Human Genetics. She is also member of the American Society of

Human Genetics, the European Society of Human Genetics, American College of Medical Genetics, and Member of

Human Genome Organisation (London). Dr. Al Arrayed is a member of the committee for studying genetics diseases in

the Arab world (Arab Health Ministers Council, Arab League, Cairo, Egypt) and Member of the committee for genetic

counseling (GCC Health Ministers Council). She is also Assistant Chief Editor in Bahrain Medical Bulletin and is found-

ing member in many societies such as Bahrain National Hereditary Anemia Society, Bahrain Child Development Society,

and Bahrain Down's syndrome Society. Dr. Al Arrayed established and directed the Bahrain Birth Defect Register proj-

ect since 1999 and the New Born Screening project 2002. She published more than 50 scientific papers, and attended

more than 90 international and national conferences. Her main interest is community and clinical genetics, and genet-

ic testing.

Genetic Diseases in Bahrain: An Overview

Shaikha S. Al Arrayed

Salmaniya Medical Complex, Ministry of Health, Bahrain

In 1983, a genetic unit was established at the Salmaniya Medical Complex (SMC), and in 1993, a national committee

for the control of hereditary diseases was established. The aim of the committee was to conduct population studies on

the prevalence of genetic diseases within the country, and to improve management and treatment standards of patients

suffering from these diseases. During these years, many studies have been carried out. In 1990 the total marriages

among relatives and first cousin marriages was 39% and 21%, respectively; while in 2002, it decreased to 24% and 12%,

respectively. Genetic blood diseases are common in Bahrain. In 2004, Sickle cell disease (SCD) was found to be the

first cause of admission to SMC; 2600 patients making up 6.5% of total admissions to SMC. The incidence of affected

newborn with beta-thalassemia is 0.02% while the trait rate remains same between 2.5 and 3.5%. The number of

Bahraini babies born with beta-thalassemia showed a decline from four babies annually to two. The frequency of glu-

cose-6-phosphate dehydrogenase deficiency seems unaltered at the level of 20-23%, but without any clinical problems.

Newborn screening in 1985, showed high frequency of alpha-thalassemia; including few patients with HBH disease and

no reported cases of hydrops fetalis. On the other hand, hemophilia is not common in Bahrain while the incidence of

chromosomal abnormalities is relatively low. On the contrary, the frequency of metabolic diseases is high and many of

affected infants die in the first or second week before the diagnosis could be established. Additionally, the mean inci-

dence of cystic fibrosis among children in Bahrain is a low 1/7700. Blindness does occur in Bahrain and the main caus-

es of congenital blindness include retinal dystrophy, glaucoma, cataract, retinopathy, and Macular degeneration. The

incidence of profoundly deaf children in Bahrain is 1.1 per 1,000 live births.


Dr. Shaikha S. Al Arrayed

37

Prof. Hans-Hilger Ropers is Director at the Max-Planck Institute for Molecular Genetics in Berlin and Professor of

Human Genetics at the Humboldt University. Between 1984 and 1997, he headed the Institute for Human Genetics

at the University of Nijmegen, The Netherlands, and since 1987, he is board-certified as Clinical Geneticist. Since

1990, his group has made numerous contributions to the molecular elucidation of monogenic disorders by posi-

tional cloning, with a focus on eye diseases, deafness and increasingly, mental retardation. His department is also

part of the European MRX Consortium which plays a central role in elucidating the molecular causes of X-linked

mental retardation, probably the biggest unsolved problem in Medical Genetics. Between 1985 and 1993, H.H.

Ropers served as Chromosome Chair and Co-Chair at several Human Gene Mapping Conferences. He is a mem-

ber of HUGO since the year of its inception and has recently been appointed as member of the HUGO Scientific

Program Committee. Dr. Ropers has served on numerous Editorial Boards and is elected member of the Royal

Netherlands Academy of Arts and Sciences and the Berlin-Brandenburg Academy of Sciences.

Genetics of Mental Retardation

Hans-Hilger Ropers

Max-Planck-Institute for Molecular Genetics, Ihnestr. 73, D-14195 Berlin, Germany

Single gene defects have an important and underestimated role in various common disorders, such as severe

mental retardation (MR), which is an enormous burden for patients, families and society. I will describe several

complementary strategies, which we have employed to elucidate the molecular basis of MR in a systematic fash-

ion. Cognitive defects are more frequent in males than in females. Therefore, research into the molecular causes

of MR has focused on the X chromosome, and collection of large cohorts of families was instrumental in identify-

ing numerous X-linked genes that play a role in cognition. Genomic imbalances, too small to be visible under the

microscope, are another common cause of MR. Using high-resolution array CGH, we and others have recently

found that submicroscopic deletions and duplications in these patients are not confined to the telomeres but can

be found in the entire human genome. Yet another successful strategy is the systematic mapping and cloning of

breakpoints in patients with balanced chromosome rearrangements, which has enabled us to identify various X-

linked and autosomal candidate genes for MR. There is reason to believe that autosomal recessive forms of MR

are common, too, but most of these disorders are sporadic, and large consanguineous families are required to map

and identify the underlying genes. Systematic studies of this kind are in progress to search for common forms of

autosomal recessive MR. Together, these studies promise to provide new insights into the function of the human

brain.

Session 2: Clinical and Molecular Genetics of Human Disease (15.00 - 15.30)


38

Dr. Habiba Bouhamed-Chaabouni is professor of medical genetics and pediatrics in University of Tunis, Tunisia

and Chief of the Department of Congenital and Hereditary Diseases, Charles Nicolle Hospital, Tunisia. She is

director of the Human Genetics Research Laboratory and the Faculty of Medicine, Tunis. Recently, Prof.

Chaabouni received the prestigious award of L'Oréal-UNESCO for Women in Science based on her groundbreak-

ing achievements and contributions to scientific progress. Prof. Chaabouni was member of the technical commis-

sion of the Arab League for Genetic Diseases Prevention and Genetic Counseling and represented Tunisia in the

Committee of Governmental Experts to prepare the draft declaration of UNESCO regarding the Human Genome.

She is member of the Société Tunisienne des Sciences Médicales, Société Tunisienne de Pédiatrie, the American

Society of Human Genetics, and the European Society of Cytogenetics. Prof. Chaabouni is author or co-author in

about 50 peer-reviewed publications.

An Overview of the Genetics of Mental Retardation in Tunisia

Habiba Bouhamed-Chaabouni


Mental retardation (MR) affects approximately 1-3% of the general population. A defining feature of MR is an intel-

ligence quotient (IQ) of less than 70. The etiologies of MR are diverse and include chromosomal anomalies, rec-

ognizable malformation syndromes, monogenic syndromes, structural brain abnormalities, and environmental fac-

tors. Biological processes entailed in signal-transduction pathways involved in neuronal maturation, establish-

ment, stabilization, and remodeling of connections between neuronal cells are important in the causation of men-

tal retardation. Taken together, chromosomal anomalies are believed to account for 4-28% of cases of MR. Most

MR patients with chromosomal anomalies have syndromic MR. Because no practical way of screening the entire

genome is available at present; efforts have first focused on submicroscopic chromosomal rearrangements such

as Williams syndrome, Di George syndrome. Other submicroscopic rearrangements involve subtelomeric regions,

1 to 8% of MR is caused by a subtelomeric rearrangement. Fragile X causes specific mental retardation while

large numbers of MR are not specific. Genetic etiologies are found in approximately two thirds of cases. A num-

ber of X linked genes associated with non-specific mental retardation have been identified, such as FMR1 and

ARX. An autosomal recessive inheritance may account for nearly one fourth of mentally retarded individuals who

do not have major physical stigmata, chromosomal anomalies, or fragile X syndrome. An autosomal recessive

mode of inheritance may account for nearly a quarter of all individuals with NSMR. Metabolic disorders are a main

cause of MR. Some autosomal locus and genes are described today. Structural brain abnormalities constitute a

main cause of mental retardation in our series. Genetic counseling may be difficult in case of absence of a known

etiology. Investigation of non acquired MR patients should help physicians and families to determine the pheno-

type cause particularly for genetic etiology. From few years we started the molecular analysis of specific and non

specific MR, both for medical facilities and for genome investigation. Applications are today available in our depart-

ment for chromosomes analysis including micro-rearrangements, and for molecular investigation.

Session 2: Clinical and Molecular Genetics of Human Disease (15.30-16.00)


39

Prof. Geoff Woods is a Pediatrician by training with interests in mental and physical handicap. He carried out an

MD on Ataxia Telangiectasia and then retrained in Clinical Genetics in Oxford. Prof. Woods then worked at the

Murdoch Institute in Melbourne Australia, then Leeds for 10 years and finally moved to Cambridge. He is a Reader

in Human Genetics, half clinical work and half time research. His clinical work involves seeing any family with a

genetic disorder, especially in his area with a substantial Pakistani population. Prof. Woods’ research work cen-

ters on finding recessive human disease genes - and then trying to work out what the gene/protein does in normal

development.

Autosomal Recessive Primary Microcephaly

Geoff Woods

Department of Genetics, Cambridge University, UK

The human brain is large, and carries an equally large requirement for energy. The advantage that it confers to

humans is assumed to be our greater intelligence and ability to adapt to almost any habitat on earth. Autosomal

recessive primary microcephaly (MCPH) is a disease where the brain growth in utero is reduced - to about the

level seen in our nearest primate relatives. The disease phenotype is microcephaly and mental retardation; the

genetics are complex recessive with eight loci; five genes have been found by us; all are centrosomal components.

We hypothesize that MCPH is a primary disorder of neurogenic mitosis. As such it will provide insights into how

the brain grows, how we may use neural stem cells and how the primate/human brain has evolved to be such a

large organ. Also, I will discuss how we can use our research findings to the benefit of affected families.


Prof. Geoff Woods

40

Rabah Mohamed Shawky is professor of pediatrics and genetics and head of the genetic unit at the department

of pediatrics at Ain Shams University, Cairo, Egypt. She is chief of the Egyptian Society of Human Genetics, the

Egyptian Society of Friends of Families of Genetic Diseases, and the Egyptian Society of Teratology. Prof. Rabah

Shawky is also member of the National Specialized Genetic Council and editor of the Egyptian Journal of Medical

Human Genetics. She published about 115 publications in scientific peer-reviewed journals mostly in the field of

human genetic disorders.

A Clinical Approach to the Dysmorphic Child

Rabah Mohamed Shawky

Ain Shams University, Egypt

The term dysmorphic designates patients with multiple congenital anomalies. The nature of the structural defect

represent clues to the time of onset, mechanism of injury, probable etiology of the problem and helps in estimat-

ing the recurrence risk. Structural defects may be of prenatal or postnatal onset. Prenatal onset problems include

single primary defect in development (malformation, deformation, disruption, and dysplasia) and multiple malfor-

mation syndromes (chromosomal, genetic, environmental, and others). Postnatal onset problems are due to

genetic, environmental, and unknown causes. The approach to the diagnosis includes proper history, three-gen-

eration pedigree, and complete physical examination including all body systems. All major and minor malforma-

tions are noted. Subjective observations should be supplemented by objective measurement and photographic

records. Cytogenetics and molecular techniques improve our ability to make a precise syndrome diagnosis.


Prof. Rabah Mohamed Shawky

41

Dr. Mohammed Naveed is a clinical Geneticist with over 15 years of experience in the field of Genetics. He is a

Diplomat of the National Board with Postgraduate Diploma (DCH) in Pediatrics. Dr. Naveed holds DM (Doctorate

of Medicine) in the field of Medical Genetics and PhD in Genetics. Dr. Naveed is a life member of the Indian

Academy of Pediatrics and associate member of the Canadian Association of Genetic Counselors, Genetic

Society of Canada, European Society of Human Genetics, and the American Society of Human Genetics. He start-

ed and offered Clinical Genetic Services at the Genetic and Thalassemia Center, Al Wasl Hospital, Dubai, for over

8 years. He also introduced Clinical Genetics as a part of the undergraduate curriculum for the Dubai Medical

College for Girls. He was the Founder Medical Director of the Canadian Specialist Hospital, Dubai. His presents

posts held at the Canadian Specialist Hospital include, Acting-Medical Director, Head of Engineering Division,

Head of Pharmacy Division, Specialist Geneticist and the Director of Laboratories.

Ectrodactyly with Aplasia of Long Bones (OMIM 119100) in a Large Inbred Arab Family with an Apparent Autosomal Dominant Inheritance and Reduced Penetrance: Clinical and Genetic Analysis

Mohammed Naveed1, Mahmoud Taleb Al Ali1, Sabitha K. Murthy, Sarah Al Haj Ali1, Najib Al Khaja1, S. K. Nath2,

S. Deutsch3, A. Bottani3, S.E. Antonarakis3, U. Radhakrishna3

1Centre for Arab Genomic Studies, P.O. Box 22252 Dubai, United Arab Emirates; 2Arthritis and Immunology

Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, United States; 3Department of

Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland

Tibial aplasia-ectrodactyly syndrome is one of the most severe defects involving the extremities. We have studied

a very large eight-generation inbred Arab family from the United Arab Emirates (UAE) with multiple severe limb

anomalies resembling OMIM; 119100, the gene of which is at present unknown. The pedigree consists of 145 indi-

viduals including 23 affected (14 males/9 females) with limb anomalies. Of these, 18 had Tibial aplasia usually on

the right side. The expression of the phenotype was variable and ranged from bilateral to unilateral Tibial aplasia

with ectrodactyly and other defects of the extremities. The mode of inheritance appears to be autosomal dominant

with reduced penetrance. There were also ten consanguineous marriages observed in this pedigree. This also

could suggest a recessive mode of inheritance with pseudodominance due to high frequency of the mutant allele.

Candidate loci for the described syndrome include the GLI3 morphopathies (GLI3; 165240) on 7p13, Sonic

Hedgehog; (SHH; 600725) on 7q36, Langer-Giedion syndrome (LGS; 150230) on 8q24.1 and Split-hand/Foot mal-

formation 3 (SHSF3; 600095) on 10q24. In addition, bilateral Tibial Hemimelia and unilateral absence of the ulna

was previously observed to co-segregate with deletion of 8q24.1. Two-point linkage and haplotype analyses did

not show the involvement of the above regions in this family. Cytogenetic and FISH analysis for the critical loci on

7p13, 7q36, 8q24.1 and 10q24, did not show any abnormality. Genome-wide linkage analysis is in progress to map

the elusive locus and provide a target for positional cloning.


Dr. Mohammed Naveed

42

Nick K Yankovsky (born 1948) is Deputy Director of the Institute of General Genetics (Moscow, Russia) at the

Russian Academy of Science, Head of Genome Analysis Laboratory at the Institute and Professor of Moscow

State University, Genetics Department where he is a lecturer in Genomics. He is HUGO Council member and

Chair of the Education committee. Prof. Yankovsky has initiated the set up of HUGO lecturer group on Genomics

for lay people and arranged an international lecturing in Genomics in Russia. He was awarded by Russian

Academy of Science with Baev prize in Genomics for his achievements in hunting for tumor suppressor genes in

human genome. Prof. Yankovsky received three annual awards from the Russian Foundation for Basic Research

for the best articles on Genomics for lay people. His current interests are in bioinformatics, adaptive traits of human

genome and gene-culture relations in humans.

Genomic Landscape Behind Common Traits of Medical Importance in Eurasia

Nick K. Yankovsky, Svetlana A. Borinskaya

Genome Analysis Laboratory, Institute of General Genetics, Russian Academy of Science, Russia

An allele of a gene is called associated with a disease if its frequency in a cohort of individuals affected with a dis-

ease is higher than the frequency in the population. The association rate is of practical importance for assessment

of risk of the disease for carriers. Association rate is a population specific feature and depends on the allele fre-

quency and genetic background, which are different in different populations. For example, ApoE e4 allele is an

Alzheimer disease risk factor for Europeans but not for Eskimo or Bushmen. In general, association rates should

be closer for neighboring populations, but you can not predict it for sure for each particular allele and disease

because each population has its own prehistory and specific mosaic of alleles and haplotypes. That is why it is of

practical importance to study general and affected cohorts in local populations for frequencies of alleles associat-

ed with common traits of medical importance. I will discuss the problems using my lab data for allele frequencies

of such genes as chemokine receptor CCR5 (protection to HIV/AIDS), apolipoprotein E APOE (risk factor of

Alzheimer’s disease and cardiovascular diseases), lactase LCT (adult-type hypolactasy), and alcohol dehydroge-

nase ADH (risk of alcoholism) gained on populations of Russia and neighboring countries with special attention to

populations neighboring to the Arab world.

Session 3: Genomics, Cancer Genetics, and Genetics of Blood Disorders (09.00-09.30)

Prof. Nick K. Yankovsky

43

Osman El-Maarri obtained his bachelor of science in Biology from the American University of Beirut (Lebanon). He

did his graduate studies in Istanbul (Turkey) where he obtained his master degree in biomedical engineering and

in 1999 his PhD in molecular biology and genetics from Bogazici University (formally known as the Robert

College). For his post-doctoral research, he moved to the laboratory of Prof. Jörn Walter at the Max-Planck

Institute for molecular genetics in Berlin (Germany), where he worked on many aspects related to DNA methyla-

tion and genomic imprinting in normal development and in disease. Since 2000, he is working at the University of

Bonn where he developed a novel quantitative method for accurately measuring DNA methylation. His main inter-

ests include blood coagulation and studies of epigenetic phenomena related to human disease

DNA Methylation: Involvement in Human Disease

Osman El-Maarri

Institute of Experimental Haematology and Transfusion Medicine, University of Bonn,

Sigmund-Freud Str. 25, 53105 Bonn, Germany

DNA methylation plays an essential role in many cellular processes including embryogenic development, gene

expression, chromosomal stability, genomic imprinting, X chromosome inactivation, and silencing of parasitic and

repetitive DNA. Abnormal DNA methylation patterns had been observed in many pathological/disease linked situ-

ations like the global hypomethylation and regional hypermethylation observed in different types of tumors; also in

imprinting disorders (like Prader-Willi, Angelman and Beckwith Wiedemann syndromes); or in diseases related to

repeats instability (like fragile X syndrome and facioscapulohumeral muscular dystrophy). Moreover, mutations in

the methylation machinery (like DNMT3B) or proteins involved in reading the methylation signatures in the genome

(like MeCP2) are the main causes for Immunodeficiency-Centromeric instability and Facial abnormalities (ICF) and

Rett syndromes, respectively. In addition, we and others have shown that a global genomic imprinting defect in the

female germ line is observed in familial recurrent biparental complete hydatidiform molar pregnancy, which is a

form of pseudo pregnancy characterized by hydropic degeneration of placental villi and abnormal or absence of

embryogenic development. The genetic defect causing this phenotype was mapped, at least in some of the affect-

ed families, to 19q13.4 and recently mutations in NALP7 gene were identified in these families. The NALP7 gene

is known to be involved in the regulation of the inflammatory process. Thus, it remains to be explained how a

mutation in an inflammation regulatory gene can affect the methylation signature at imprinted genes in the female

germ line.

Session 3: Genomics, Cancer Genetics, and Genetics of Blood Disorders (09.30 - 10.00)

Dr. Osman El-Maarri

44


Prof. Lotfi Chouchane

Dr. Lotfi Chouchane is professor in the departments of genetic medicine, and microbiology and immunology of

Weill Cornell Medical College. Dr. Chouchane received his Ph.D. in immunology from Pasteur Institute of Paris

and the University of Paris VII. Following a four-year post-doctoral position at the National Institute of Allergy and

Infectious Diseases, National Institutes of Health, in the U.S., he obtained his D.Sc. in human genetics and

immunology. He then joined the National Institute of Medical Research in Paris as senior scientist. Dr. Chouchane

was professor of human genetics and immunology, and chief of the laboratory of immuno-oncology at the Faculty

of Medicine and chairperson of the department of basic science at Monastir University (Tunisia). In 2004, he was

appointed as scientific advisor to the Minister of Scientific Research and Technology of Tunisia, coordinator of the

European Commission program and member of the steering committee of the National Center for Cancer

Research. Dr. Chouchane is a member of the steering committee of the WHO consortium of genetics of nasopha-

ryngeal cancer. His current research interests include the genetics and immunology of multi-factorial diseases,

including cancer.

The Genetics of Breast Cancer: From Biology to Clinical Applications

Lotfi Chouchane

Laboratoire d’Immuno-Oncologie Moleculaire, Faculte de Medecine de Monastir, Tunisia


Breast cancer is a common genetic malignancy affecting women around the world. It occurs in hereditary and spo-

radic forms. A family history of breast cancer is one of the main risk factors in the development of the disease.

About 5-10% of all breast cancer is inherited as the result of highly penetrant germline mutation in cancer predis-

posing genes, which leads to an autosomal dominant predisposition to the disease. Two major susceptibility genes

have been identified. BRCA1 was the first locus associated with inherited, early-onset breast cancer. BRCA1 is

also responsible for inherited susceptibility to ovarian cancer. Subsequently, a second breast cancer susceptibili-

ty gene, BRCA2, was identified on chromosome 13q.12. Studies of allelic loss in tumors from families affected with

breast and ovarian cancer suggest that BRCA1 is a tumor suppressor gene. Mutations in BRCA1 gene are dis-

tributed throughout the coding region. Vast majority of these mutations have been identified as frameshift, non-

sense or splice site alterations that lead to premature protein truncation. The presence of recurrent mutations in

BRCA1 suggests the presence of founder effects; this was first confirmed in the Ashkenazi Jewish population. We

investigated the presence of BRCA1 germline mutations and potential existence of population-specific recurrent

mutations in Tunisian breast cancer families. Breast cancer prognosis differs among racial and ethnic groups.

While socioeconomic, psychosocial, and lifestyle issues are undoubtedly important in such disparities, genetic fac-

tors that differ among populations and that are involved in the molecular pathways regulating tumor development

may also play roles. In this communication, I summarize recent investigations of the genes encoding pro-inflam-

matory cytokine such as IL-6, IL-1 and TNF-α and suggest that their genetic variation may predict not only breast

cancer onset but also the clinical outcome.

45


Prof. Riad A. Bayoumi

Professor Riad Bayoumi is Chairman of the Department of Clinical Biochemistry, College of Medicine, Sultan

Qaboos University, Muscat, Oman. He graduated from Khartoum Medical faculty (1967) and obtained PhD in

Biochemistry from London University (1973). Prof. Bayoumi is elected member of the Royal College of patholo-

gists (1975) and a fellow of the same College in 1995. He has extensive experience in clinical biochemistry and

molecular biology teaching and research. His main research interest is in population genetics, mapping of mono-

genic and complex polygenic diseases. Prof. Bayoumi mapped Joubert Syndrome, Spastic Paraplegia, and

spondyloepiphyseal dysplasia. At present, he is involved in the study of hypertension, diabetes and obesity in large

extended and highly consanguineous Omani pedigrees.

Molecular Diagnosis of Chronic Myeloid Leukemia

Riad A. Bayoumi

Clinical Biochemistry Department, College of Medicine and Health Sciences,

Sultan Qaboos University, Muscat, Oman

Chromic Myeloid Leukemia (CML) is a clonal stem cell disorder in which proliferation of myeloid elements occurs

at all stages of differentiation. The disease is due to a translocation between chromosomes 9 and 22; t(9;22),

[p34.1; q11.21]. The hybrid Ch 22 has been named the Philadelphia Chromosome (Ph). The ABL proto-oncogene

on Ch 9 is reciprocally translocated near the BCR gene on Ch 22, resulting in the formation of a chimeric gene the

BCR-ABL. The fusion protein is expressed as a chimeric protein with tyrosine kinase activity. Understanding the

role of BCR-ABL protein in oncogenesis and the molecular pathology of CML has made CML one of the first cur-

able cancers, with a wide variety of diagnostic tests, a novel designer-drug and sensitive measures for follow-up

of drug therapy and prognosis. The repertoire of molecular diagnostics include PCR demonstration of Ph

Chromosome, detection of the various forms of the BCR-ABL fusion transcripts using RT-PCR, follow-up and

detection of minimal residual disease, and the follow-up of treatment using various therapies including Gleevec

and bone marrow transplants.

46


Dr. Erol A. Baysal

Dr. Erol Baysal has been working as Consultant Molecular Biologist and Head of the Molecular Genetics Unit at the

Genetic and Thalassemia Center, Department of Health and Medical Services since 1995. He obtained two graduate

degrees with honors from UCLH and RFHSM, University of London. After his doctorate at Royal Free Hospital, London,

in 1987, he worked as a postdoctoral fellow at the NYU Medical Center in USA. In 1994, he was elected to New York

Academy of Sciences as a lifetime member. He received scholarships and numerous awards during his education and

training in the UK and USA. He was appointed as Assistant Professor in 1989 at the Medical College of Georgia, USA,

where he held several posts including teaching, research and as PhD advisor in the graduate faculty. He also served

as university senator. He was the PI in three extramural grants and co-investigator in three NIH grants. For 10 years,

he worked as Head of the DNA Laboratories at the National Hemoglobinopathy Reference Center in Augusta, USA. Dr.

Baysal authored and co-authored more than 70 publications in peer-reviewed journals of the mainly on inherited blood

disorders and is co-author of one of the most frequently-cited reference books; The Thalassemia Syllabus (1997).

Hemoglobin Disorders in the United Arab EmiratesErol A. Baysal, Iqbal Yousuf, Mahnaz Zeinali, Halya Abdullah, Mona Essa, Gloria Garcia, Hala Aouda, Ruqaya

Mohammed, Riad Jaber, Alya Al Ghazal, Eman Daban, Mahmoud Taleb Al Ali

Genetic and Thalassemia Center, Genetics Department, Al Wasl Hospital, Department of Health and Medical Services,

Dubai, United Arab Emirates

During the last 10 years we performed mutational analysis on 772 β−thalassemia patients at the Genetic and

Thalassemia Center, Al Wasl Hospital. Approximately half of the patients were UAE nationals and the other half were

Indians, Pakistanis, other Arab nationals, Africans and Iranians. A total of 479 patients (62%) were homozygous for

β−thalassemia. This accounted for approximately two thirds of our patient population. The remaining 293 (38%) were

compound heterozygotes. Approximately one third of the patients (32%) were homozygous for the IVS-I-5 (G-C) muta-

tion. This was followed by the sickle cell disease where patients were homozygous for the sickle cell gene (βS). Co-

inheritance of both alleles i.e. HbS/IVS-I-5 (G-C) were found in 37 patients (4.8%). Another common mutation was the

frameshift Cd 8/9 (+G). A total of 29 patients (3.8%) were homozygous for this extremely severe mutation. As few as

three β-thalassemia mutations; IVS-I-5 (G-C), (βS and Cd 8/9 (+G), accounted for 52.1% of the patients whereas 12

mutations defined 75% of the patients at the molecular level. Majority of the patients were characterized with the most

severe mutations. DNA diagnostic approaches ranged from PCR, Dot Blot Hybridization, Reverse Dot Blot

Hybridization, Restriction Enzyme Digestion, Direct PCR detection, Amplification Refractory Mutational System (ARMS),

Manual and Automated DNA Sequencing. The results indicate that the frequency of β−globin gene defects including

β-thalassemia, sickle gene (βS) and abnormal hemoglobins represent one of the highest in the world. The number of

homozygous patients strongly suggests high degree of consanguinity among the UAE nationals as well as the expatri-

ates most of whom were Muslims. Thus far, we have characterized 51 different β-thalassemia alleles in the UAE, which

makes it arguably the most heterogeneous population in the world. The diversity of these mutations reflects the histor-

ical admixture of genes and their migration from different areas in the region. Our data strongly suggest the need, in the

UAE, for a comprehensive thalassemia control program and provides a basis for population screening, genetic counsel-

ing and prenatal diagnosis.

47


Prof. Adekunle D. Adekile

Dr. Adekunle Adekile had his medical education in the University of Ibadan Nigeria. He had his pediatrics residen-

cy training in Nigeria and post-doctoral training in Pediatric Hematology in Howard University, Washington DC.

Between 1990 and 1993, he was a Forgarty International Research Fellow in Molecular Genetics at the Medical

College of Georgia, Augusta GA, USA under Prof. Titus Huisman. He is a fellow or member of numerous profes-

sional and academic bodies. He holds a PhD in cell biology form the University of Maastricht, Netherlands.

Dr. Adekile’s research interest is in the area of clinical and molecular characterization of hemoglobinopathies,

especially sickle cell disease. He has published studies on patients from Nigeria, United States of America, and

Kuwait. He is currently Director of the Hemoglobin Research Laboratory and Professor/Chairman, Department of

Pediatrics, Kuwait University.

Clinical Implications of the Arab S-Globin Gene Haplotype

Adekunle D. Adekile

Department of Paediatrics, Faculty of Medicine, Kuwait University

The phenotype of sickle cell disease (SCD) is very variable with some patients having a mild and others a severe

clinical course. Several factors have been identified for this and the most widely studied are the βS-globin gene

haplotype, level of fetal hemoglobin (Hb F) and co-existent α-thal trait. Most Kuwaiti patients carry the Arab βS

haplotype, which is associated with high Hb F levels and a relatively mild clinical course. More than 90% of our

patients are homozygous for the Arab βS-globin gene haplotype, characterized by a +ve Xmn-I site in the Gγ-glo-

bin gene promoter. About 37% have co-existent α-thal trait. Details of the phenotypic characteristics and clinical

course in these patients are still being elucidated. Over the past 10 years, we have carried out systematic,

prospective clinical studies of SCD patients (mostly children) being followed in Mubarak and Amiri Hospitals in

Kuwait. Results of genotype characterization, spleen function and pulmonary function, prevalence of brain infarcts

and avascular necrosis of the femoral head will be summarized and compared to reports from other parts of the

world. Using radio-labeled colloid and denatured RBC splenic scintigraphic studies, we showed that about 75% of

SCD patients between the ages of 6 and 16 years maintain full or partial splenic function. Pulmonary function stud-

ies showed an early restrictive pattern in children with SCD compared to normal controls. Magnetic resonance

imaging (MRI) studies showed that the prevalence of avascular necrosis of the femoral head is about 25%, but

subclinical brain infarcts were seen in only 3.3%. These studies show that while the overall phenotype in Kuwaiti

SCD patients may be mild, there is still considerable heterogeneity. Bacterial infections are uncommon mainly

because of sustained spleen function. It is rather surprising that restrictive pulmonary function is demonstrable in

children. It is also interesting that while bone infarcts are quite common, brain infarcts are rare in our SCD chil-

dren. There is a need for collaborative studies in the GCC to further characterize the sub-phenotypes of the dis-

ease and correlate these with novel polymorphisms in key proteins involved in anti-oxidant pathways. This is the

current emphasis now that SCD is being viewed more as an inflammatory disease.

48



Dr. Habiba Bouhamed-Chaabouni is professor of medical genetics and pediatrics in University of Tunis, Tunisia

and Chief of the Department of Congenital and Hereditary Diseases, Charles Nicolle Hospital, Tunisia. She is

director of the Human Genetics Research Laboratory and the Faculty of Medicine, Tunis. Recently, Prof.

Chaabouni received the prestigious award of L'Oréal-UNESCO for Women in Science based on her groundbreak-

ing achievements and contributions to scientific progress. Prof. Chaabouni was member of the technical commis-

sion of the Arab League for Genetic Diseases Prevention and Genetic Counseling and represented Tunisia in the

Committee of Governmental Experts to prepare the draft declaration of UNESCO regarding the Human Genome.

She is member of the Société Tunisienne des Sciences Médicales, Société Tunisienne de Pédiatrie, the American

Society of Human Genetics, and the European Society of Cytogenetics. Prof. Chaabouni is author or co-author in

about 50 peer-reviewed publications.

Genetics of Familial Mediterranean FeverHabiba Bouhamed-Chaabouni


Familial Mediterranean Fever (FMF) is one of the periodic fever syndromes, and is extremely common in

Mediterranean countries. It is an autosomal-recessive disorder characterized by recurrent, short, self limited and

painful episodes of fever and polyserositis. The gene responsible for FMF, MEFV, was identified by positional cloning

in 1997. It is located on chromosome 16p13.3, comprises 10 exons and 781 codons. The product of MEFV gene,

named pyrin/Marenostrin is expressed in polymorphonuclear cells and monocytes and it is proposed that it regulates

inflammatory responses at the level of leukocyte cytoskeleton organization. After identifying the first four mutations,

several other mutations including E148Q have been identified in the MEFV gene as the disease causing mutation.

Ninety-four mutations located in the MEFV gene have been identified so far; mostly in exon 10 followed by exons 2,

3, 5, 1 and 9. Four of five founder mutations, M694V, V726A, M680I and M694I are located in exon 10 and E148Q

in exon 2. These founder mutations account for 74% of FMF chromosomes in typical patients from the

Mediterranean. Four populations are commonly affected with FMF: Arabs, Armenians, Non-Ashkenazi Jews and

Turks. The carrier rate in these populations is extremely high and ranges from 1 in 6 to 1 in 3. One in three in

Armenia... The theoretical prevalence of the genetic disease can be deduced from this carrier rate and ranges from

1 to 6%. These data show that FMF is not an orphan disease as thought previously. Several studies have been per-

formed and showed that MEFV mutations profile is quite different in FMF patients even inside the same ethnic group.

For example the most common mutation in Tunisian population is M680I, the allele frequency is 31.77%, which is

the highest percentage that have been reported today. While it has been reported in Arabs and accounted for almost

10% to 17% of the identifiable mutations. Molecular epidemiology of MEFV mutations will be presented with com-

parison between different populations. The clinical panel associated with MEFV mutations ranges from total absence

of symptoms (incomplete penetrance) to amyloidosis. The general trend is that mutations E148Q, V726A are asso-

ciated with low penetrance and low risk of amyloidosis, while patients with mutations at codons 694 or 680, or a com-

bination of these mutations have a high risk of amyloidosis. Presymptomatic diagnosis may be relevant in popula-

tions frequently affected by FMF. But the main indication remains post symptomatic diagnosis, especially in patients

with atypical signs. Early diagnosis is important to give patients relevant treatment and avoid complications.

49

Session 4: Cytogenetics, Consanguinity and Bioethics (14.00 - 14.30)

Prof. Sue Povey

In 1964, Prof. Sue Povey received a BA in Natural Sciences (genetics) at Cambridge. After clinical studies at UCH

she qualified in medicine in 1967 and went on to work for the Save the Children Fund in Algeria. In 1970 she

returned to take up a scientific post in MRC Human Genetics at University College London (UCL) where she

worked until 2000. She is now Haldane Professor of Genetics at UCL. Her long term interests are in identification

of human genes, building of genetic maps and in the disease Tuberous Sclerosis, however her main effort now is

in gene nomenclature where she is chair of the HUGO Gene Nomenclature Committee.

Progress towards the Understanding and Treatment of Tuberous sclerosis

Sue Povey

Department of Biology, University College London, UK

This autosomal dominant disorder occurs worldwide and has a prevalence of about 1 in 10,000 at birth, with 70%

of cases being sporadic as a result of new mutations. It is characterized pathologically by the presence of benign

tumors known as hamartomas, which occur in many organs. Major clinical features are epilepsy, learning disabil-

ity, behavioral problems and skin lesions but renal angiomyolipomas are also frequent. The disease shows high

penetrance but is extremely variable even within the same family. It is caused either by defects within TSC1 on

chromosome 9 encoding hamartin or TSC2 on Chromosome 16 encoding tuberin, with defects in TSC2 on aver-

age (but not always) producing more severe disease. In the past five years work in Drosophila and then rodents

has dramatically increased our understanding of the function of the complex formed by the hamartin and tuberin

proteins in a conserved signaling pathway regulating cell growth. A critical function is the regulation of the mam-

malian target of rapamycin, mTOR through control of the activity of Rheb, (member of the RAS family enriched in

brain). This suggested the possibility that rapamycin might be a useful therapy. Following encouraging results with

rodent models, clinical trials in patients are now in progress.

50

Session 4: Cytogenetics, Consanguinity, and Bioethics (14.30 - 15.00)

Prof. Laila Zahed

Dr. Laila Zahed is Associate Professor in the Department of Pathology and Laboratory Medicine and Director of

the Cytogenetics Laboratory, at the American University of Beirut Medical Center. She has a BS in Biology from

the American University of Beirut and an MS in Human Genetics from the University of Michigan, Ann Arbor, USA.

She completed her PhD at Guy’s Hospital, University of London, England and a post-doctoral research fellowship

at Montreal Children’s Hospital, McGill University, Canada. Since 1992, she has been a faculty member at the

American University of Beirut and director of the Cytogenetics Laboratory. Dr. Zahed has published numerous arti-

cles on clinical Cytogenetics, β-thalassemia mutations, and the acceptance of prenatal diagnosis in Lebanon. She

is a member of a variety of genetics associations and the country coordinator for ECARUCA, the European

Cytogenetics Association Registry for Unbalanced Chromosome Abnormalities.

Cytogenetics Services, Quality Management and Challenges

Laila Zahed

American University of Beirut Medical Center, Lebanon

Chromosome abnormalities occur in an estimated 0.7% of newborns and 50% of first-trimester abortions. They

play a major role in malignancies and the risk of a chromosomal abnormality is the major referral category for pre-

natal diagnosis. Chromosome analysis is therefore the most frequently requested genetic test while it is the one

most affected by subjective interpretation. Despite the development of Molecular Cytogenetic techniques of

increasingly higher resolution, conventional chromosome analysis, through cell culture and karyotyping, is still

widely used. Training in Cytogenetics is a lengthy process and strict guidelines for quality management and con-

trol have to be followed. Laboratories in the region are faced with particular challenges relating to these aspects.

Coordination and collaboration between laboratories, following the example of laboratories in Europe, may help

overcome some of these limitations.

51


Prof. Jon Andoni Urtizberea

Prof. Jon Andoni Urtizberea is currently the Research Director at the European Neuromuscular Centre (ENMC),

The Netherlands. He obtained his medical degree from University of Paris (Lariboisiere - St. Louis) followed by a

degree in tropical medicine from University of Aix-Marseille (France), and a degree in political sciences from Institut

d’Etudes Politiques de Paris. Prof. Urtizberea was medical director of the Muscular Dystrophy Association (AFM)

in France, general secretary of the Institute of Myology (Paris, France), Professor of Physical Medicine and

Rehabilitation, UVSQ, head of the Department of Physical Medicine and Rehabilitation at Garches Hospital, and

head of the Division of Myology at the Muscular Dystrophy Association in France. Prof. Urtizberea is author or co-

author in about 50 publications in peer-reviewed journals mainly focusing on neuromuscular disorders.

New Challenges for Neuromuscular Diseases in the Middle East

J. Andoni Urtizberea

European Neuromuscular Center, Baarn, The Netherlands

Hopital Marin, Assistance Publique Hopitaux de Paris, 64700 Hendaye, France

Neuromuscular diseases constitute a heterogeneous group of conditions, the majority of which are genetically

determined. In addition to Duchenne muscular dystrophy (DMD) and spinal muscular atrophies (SMA), two para-

digmatic and rather common conditions in childhood, still exist a myriad of less frequent, somehow orphan, neu-

romuscular diseases affecting all ages. After decades of primarily clinical descriptions (1868-1987), substantial

progress have been made recently (1987-2003) to identify the genetic underlying defects thanks to molecular biol-

ogy. This led to a revised classification of neuromuscular diseases with many novel proteins, including dystrophin,

the one discovered in 1987, being shown to cause muscular dystrophy. This tedious work is not yet completed,

though. In extremely rare myopathies or neuropathies, sometimes only reported in a small set of families, cloning

the defective gene remains very challenging. In parallel, and based on the new insights into the pathogenesis of

some of these disorders, a couple of clinical trials have been initiated (2003-2006). Gene and cell therapies have

slowly moving from bench work to bedside, mostly in the West, while more classical pharmacological trials could

be theoretically set up universally. In communities faced traditionally and culturally with numerous consan-

guineous marriages, neuromuscular diseases as a whole can represent up to 25% of requests for genetic coun-

seling. It is therefore a growing concern both in the Middle East and in the Gulf. The question of prevention and

early detection of carriers is clearly posed, notably in SMA. Training experts in the field is also a challenge. Another

concern relates to autosomal recessive muscular dystrophies, where genetic heterogeneity is the rule and where

access to accurate diagnosis is not yet a reality in most countries of the region. Joining forces and mutual collab-

oration are required to tackle these obstacles and should be best conducted at the regional level. Patients’ advo-

cacy groups, when they exist, could also play an important role, as they did, notably in France, by promoting

research and optimal care in these often devastating diseases.

52


Prof. Hanan Hamamy

Dr. Hanan Hamamy is professor of Human Genetics and Specialist in charge of the Genetic Counseling clinic at

the National Center for Diabetes, Endocrinology and Genetics in Amman/Jordan, and Consultant Medical

Geneticist at Jordan University Hospital. She was professor of Human Genetics at Mustansiriyah Medical College

in Baghdad (Iraq), and Specialist in charge of the Counseling Clinic and Cytogenetics Laboratory at Yarmouk

Teaching Hospital, Baghdad (Iraq). Dr. Hamamy obtained her MBChB degree from Alexandria University (1973)

and her MS degree in Human Genetics from Edinburgh University (1976). She has more than publications in

International and Arab literature on genetic disorders, consanguinity and genetic services in Arab countries. Dr.

Hamamy participated in several World Health Organization consultations and co-authored several WHO publica-

tions on community control of genetic and congenital disorders, ethical issues in medical genetics, and prevention

and care of genetic diseases and birth defects in developing countries.

Consanguineous Marriages in the Arab World

Hanan Hamamy

National Center for Diabetes Endocrinology and Genetics, Amman, Jordan

Consanguinity continues to attract attention among medical and population geneticists, clinicians and social sci-

entists. The decline in infant mortality rates in most Arab countries through the improvement in childhood nutrition-

al status and combating infectious disease means that genetic disorders will be assuming an ever-increasing

importance. In all Arab countries, consanguineous marriage is widely practiced and is culturally preferred, which

means that recessive genetic disorders will continue to gain greater prominence in the overall spectrum of ill

health. Most research in the field of consanguinity has been directed to elucidate its deleterious effects on the fetus

and the infant. There is limited research on the association of consanguinity with non-communicable diseases and

on the social effects of consanguinity in Arab countries. Increasing numbers of couples seeking premarital coun-

seling regarding consanguinity are seen in genetic counseling clinics. There is a need to design a wide range of

multidisciplinary investigative approaches to assess the advantages and disadvantages of consanguinity on health

and social structure of Arab populations. Current knowledge of consanguinity in the Arab World and suggestions

for future research will be presented.

53


Dr. Andre Megarbane

He is associate professor of medical genetics and head of the Medical Genetic Unit, St Joseph University,

Lebanon. Dr. Megarbane is author and co-author of more than 130 publications. He is member of the Bioethics

Committee of the Lebanese Order of Physicians, member of the French Society of Genetics and Genetic

Counseling, the American Society of Human Genetics, and the European Society of Human Genetics. Dr.

Megarbane is member of the editorial board of the European Journal of Medical Genetics and member of the

Rammal Rammal Prize committee. He is recipient of four scientific awards, namely: Abdel Hamid Shuman award;

Rammal Rammal Medal, Mohammad El-Fasi young researcher, and Makhzoumi Association award. Dr.

Megarbane has an active research with interest in the domains of mental retardations, dysmorphology, osseous

malformations, and others.

Interest of Consanguineous Families in the Understanding of

Genetic Disorders: Lebanese Cases

Andre Megarbane

St Joseph University, Beirut, Lebanon

Mapping of genes involved in rare autosomal recessive diseases is difficult because of the lack of families with

more than one affected progeny. The use of identity-by-descent (IBD) method in consanguineous families can

overcome this problem. It can provide a rapid means of mapping autosomal recessive genes by identifying

chromosomal regions that show homozygous segments by descent in samples of inbred affected individuals. As

a single affected child of a first-cousin marriage can provide the same total information about linkage as a nuclear

family with three affected children, it should be possible to map a recessive disease gene by studying DNA from

fewer than a dozen unrelated, affected inbred children. Consequently, IBD is a powerful tool to map recessive

diseases for which it is impractical or impossible to collect adequate numbers of families with multiple affected

offspring. Thus, populations with high rates of consanguinity are important for cloning genes involved in rare

autosomal recessive disorders. We will detail how some such Lebanese families helped in the discovery of more

than 30 genes.

54


Dr. Aida Ibrahim M. Al Aqeel

Dr. Aida Al Aqeel is Senior Consultant Pediatric Metabolist, Geneticist, and Endocrinologist at the Riyadh Armed

Forces Hospital and Adjunct Senior Scientist at the King Faisal Specialist Hospital and Research Centre (Saudi

Arabia). She graduated from Kuwait University, Kuwait with MD in medicine and Surgery and BS in Biochemistry

with honors. Dr. Al Aqeel completed her pediatric residency training, obtained the Membership of the Royal

College of Physicians of the UK (1987), and obtained the Fellowship of the Royal College of Physician of London

and Edinburgh (1994). She is a member of several prestigious societies and received several awards including

the Outstanding Investigation Award from the American Federation of Medical Research (2002) and the Out

Standing Science Award from European Society of Human Genetics (2005). Dr. Al Aqeel is actively involved in

research for diagnosis, treatment and application of molecular genetics and genomics, in prevention of genetics

disorders including neurodegenerative disorders either by carrier testing, prenatal or preimplantation diagnosis.

She published over 50 manuscripts on neurometabolic genetic disorders in peer-reviewed medical journals.

Islamic Perspective on Human Cloning, Stem Cell Research and

Pre-implantation Genetic Diagnosis (PGD)

Aida Ibrahim M. Al Aqeel

Department of Pediatrics, Riyadh Armed Forces Hospital, Riyadh

King Faisal Specialist Hospital and Research Centre, Riyadh, Kingdom of Saudi Arabia

We are at a time of unprecedented increase in knowledge of rapidly changing technology. Such biotechnology

especially when it involves human subjects raises complex ethical, legal, social and religious issues. A WHO

expert consultation concluded that “genetics advances will only be acceptable if their application is carried out eth-

ically, with due regard to autonomy, justice, education and the beliefs and resources of each nation and commu-

nity”. Public health authorities are increasingly concerned by the high rate of births with genetic disorders espe-

cially in developing countries where Muslims are a majority. Therefore, it is imperative to scrutinize the available

methods of prevention and management of genetic disorders. Islam is a religion which encompasses the secular

with the spiritual, the mundane with the celestial and hence forms the basis of the ethical, moral and even juridi-

cal attitudes and laws towards any problem or situation. Islamic teachings carry a great deal of instructions for

health promotion and disease prevention including hereditary and genetic disorders, therefore we will discuss how

these teachings play an important role in the management and preventive measures. Stem cells are important

therapeutic modalities for many oncological, genetics, chronic disorders; we will discuss our experience in that and

how Islamic teachings makes this very promising, research and therapeutic, ethically debatable modality of treat-

ment permissible, and the Islamic views of cloning. Pre-implantation Genetics Diagnosis (PGD) is a technique that

allows the determination of genotype of embryo before implantation. It avoids the difficult decision of whether or

not to terminate the pregnancy (Prenatal Diagnosis), our experience with over thirty patients that it is an important

therapeutic and research preventive measure for many genetics disorders, whether early or late onset disorders.

55

56

Phenotypic Variations versus Genetic Differences in the

Oral-Facial-Digital Syndromes

Mona El Ruby

The National Research Centre, Cairo, Egypt

Oral- facial- digital (OFD) syndromes are a heterogeneous group of inherited disorders that have in

common anomalies of the face (median cleft lip), oral (bifid or lobulated tongue with hamartomas)

and digits (brachydactyly and polysyndactyly). Due to variations of subtle clinical features, up to 11

types have been proposed to date. In this study we report on 11 affected cases from 2 unrelated

Egyptian families with the OFD phenotype. All the index cases presented the clinical and radiologi-

cal features of the phenotype but with variable degrees and overlapping features of the different

OFD "syndromes". Some of our cases showed previously unreported findings and unusual manifes-

tations which possibly represent new variants of the OFD "syndromes" or broaden its phenotypic

spectrum. Our study emphasizes the difficulties in making a precise classification because of the

phenotypic overlap in the presently reported types. For practical genetic counseling we suggest a

broad classification of OFD "syndromes" into two major categories: The X-linked OFD syndrome

(Type I) and an autosomal recessive (AR) group comprising the other types. Because of parental

consanguinity and affected sibs, the two families we are reporting fall in the category of (AR) types.

Main features of our cases and their comparison to previously reported types will be discussed.

Since the gene for the X-linked OFD variant has been identified, we recommend molecular genetic

studies of (AR) types of OFD syndrome to clarify the existing phenotypic dilemma.

57

Inherited Thrombotic Risk Factors in non-Selected Group of Egyptian Population

Ezzat Elsobky1, S.M. Elsayed1, A. Ulu2, Z. Yıldız2, M. Tekin2, N. Akar2

1Pediatric Hospital, Ain Shams University and Medical Genetics Center, Cairo, Egypt; 2Pediatric

Molecular Genetics Department of Ankara University, Turkey

In recent years, knowledge concerning inherited and acquired causes of thrombophilia has greatly

increased. The association of venous thromboembolism is reported to be different according to the

genotype, being higher among the carriers of natural anticoagulant deficiencies and homozygotes

for factor V Leiden. The aim of this study was to evaluate the incidence of five inherited thrombot-

ic risk factors (FV1691A, FV4070G, PT20210A, EPCR 23 bp insertion and ACE 300 bp deletion) in

non-selected group of healthy individuals. The study included one hundred and twenty randomly

selected healthy individual with age ranged from 1 to 62 years. This included 32 children (15 males

and 17 females with age rang between 1 and 18 years with mean of 13.29 years) and 90 adults (32

males and 58 females with age range between 18.5 years and 62 years with mean of 33.52 years).

The study revealed that 18 individuals (15%) had FV1691A mutation with a frequency of 0.075. R2

and R3 haplotypes were found in 15 (12.5%) and 2 (1.6%) individuals, respectively. Two of them

carried FV1691A and R2 haplotype at the same time. Only one individual had EPCR 23 bp inser-

tion in heterozygous form (0.83%). None of the 120 individuals had PT 20210A mutation. The dis-

tribution of angiotensin converting enzyme -300 bp del in homozygous state was present in 61

(50.8%) individuals. The frequency of DD allele was 0.508. Neither age nor sex was found to affect

the distribution of this mutation. In conclusion, our preliminary data reveal that FV1691A mutation is

an important risk factor for thrombosis in Egyptians and further studies on a larger scale population

are needed.

58

Nutrigenomics A New Era of Therapeutic Nutrition

Mona H. Fouda

Life Medical Center, Abu Dhabi, United Arab Emirates

Ministry of Health, Alexandria, Egypt

Nutrigenomics: is the study of the interaction and influence of nutrients on gene expression and

resulting health outcomes. Human development depends on genetic and environmental factors. A

person's genetic information is carried in the DNA of the chromosomes and mitochondria. Most dis-

eases probably have some genetic component, the extent of which varies. Environmental factors

may alter genetic information through mutation or other factors e.g. dietary management in

Phenylketonuria, drugs and diet modification for hypercholesterolemia. There has been an increase

in the use of concepts evolved from molecular biology in the study of food components and essen-

tial nutrients as factors in the control of gene expression for e.g. Polyunsaturated fatty acids (PUFA)

especially Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in the form of fish oils

suppress the hepatic mRNA production of fatty synthase for lipoproteinemia which helps in reduc-

ing the incidence of cardiovascular diseases. Hence nutrition plays an important role in modification

of genetic diseases which is classified into three types: (1) Single gene (Mendelian) inheritance, (2)

Chromosomal genetic disorders, and (3) Multifactorial inheritance.

59

An Egyptian Experience of Phenylketonuria (PKU) Involving 100 Families

Laila Effat

Department of Medical Molecular Genetics, National Research Center NRC, 12622 Giza, Egypt

Extensive data have been published during the last two decades about PKU from many countries,

describing the scope and problems of screening to the mutational make-up of in these countries. A

joint team effort at the National Research Center is focusing on the different issues of phenylke-

tonuria to complete a comprehensive picture and solve problems with the least economic expense.

Screening program is still debated by the ministry of health due to issues of incomplete database

indicating the actual frequency and the cost effect due to high management costs needed to be

offered to these patients. Diagnosis is based on a colorimetric method by ELISA. The clinical group

offers genetic counseling, guided diet management, growth and neurological assessment and IQ

evaluations. Molecular studies targeting six mutations (IVS10, R261Q, R252W, Y277D, E221G and

V245V) was persued by PCR and restriction enzyme assays with aim of identifying the most preva-

lent mutations. The results revealed the presence of IVS10 (17%), V232V (17%) and R261Q (7%).

Additional data was revealed from a pilot study identifying a variety of mutations and confirming that

IVS10 and R261Q were the most prevalent. VNTR studies were also attempted to strengthen clues

of targeting specific mutations. Repeat units 9, 8, 7 were the most common found among the PKU

population whereas 9, 3, 7 among the normal individuals. Small-scale manufacturing was initiated

to locally produce low phenylalanine food and milk products with promising success. A support

group was organized to offer help to PKU families and to raise the awareness and knowledge of

PKU in the community, particularly the issue of preventing mental retardation by early diagnosis.

This multifaceted approach lays background for future implementation of PKU screening program in

Egypt and sets an example for tackling this problem in the Arab world.

60

Genetic Study of Two Patients with Neonatal Progeroid Syndrome

Sawsan A. Hassan, Areeg El-Gharbawy, Hoda Abdelghany

Genetic Unit, Cairo University, Egypt

Two sibs with progeroid features: the first child is a male aged 7 years old with mental retardation

and progeroid features except the hair is preserved despite sparse, his female sister is 4 months old

with similar features (progeric facies, marked wasting, sparse hair, prominent veins), a third sister

with similar features died at the age of 6 months after what seems to be an attack of gastroenteri-

tis, the couple have one normal child aged 11 years old and are not consanguineous. The clinical

features and course are suggestive of neonatal progeria (pseudohydrocephalic progeria).

Wiedemann-Rautenstrauch syndrome is a rare disorder with a progressive course and early lethal-

ity. Severe mental and growth retardation, muscle hypotonia, a progeroid face, wrinkled skin, rela-

tive macrocephaly with late closure of the anterior fontanel, arachnodactyly and congenital heart

defects are also typical. If there is a way to do a linkage study that would be great as the gene locus

for this syndrome is not known.

61

Mutations in OTOTARA, a Novel Isoform of TARA (Trio-Associated Repeat on

Actin) are Responsible for Recessive Non-Syndromic Hearing Loss DFNB28

Hashem Shahin1,2, Tom Walsh3, Mary-Claire King3, Moein Kanaan2, Karen Avraham1

1Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv

University; 2Department of Life Sciences, Bethlehem University, Bethlehem, Palestinian Authority;

3Department of Medical Genetics, University of Washington, Seattle, WA

In a large consanguineous Palestinian kindred, we mapped DFNB28, a locus associated with reces-

sively inherited, prelingual profound sensorineural hearing impairment, to chromosome 22q13.1.

We report here that mutations in a novel 219 kD isoform of TARA (Trio-Associated Repeat on Actin)

are associated with DFNB28 in a total of nine Palestinian families, we refer to this isoform as OTO-

TARA. Two nonsense mutations (R347X and Q581X) truncate the protein and a potentially delete-

rious missense mutation (G1019R) occurs in a conserved motif in a putative SH3 binding domain.

In seven families, 27 deaf individuals are homozygous for one of the nonsense mutations; in two

other families, three deaf individuals are compound heterozygotes for the two nonsense mutations

or for Q581X and G1019R. We screened the three TARA mutations in 300 unrelated Palestinian

hearing controls from different areas of the West Bank; one individual was heterozygous for

G1019R; no one carried R247X or Q581X. Based on the families reported above, the frequencies

of the three mutant alleles among the 156 probands with hereditary hearing loss were 0.029 for

R247X, 0.032 for Q581X, and 0.003 for G1019R. The novel, long isoform of TARA (OTOTARA)

showed expression in a number of tissues, including cochlea, retina, and fetal brain, whereas the

original short isoform is widely expressed. Antibodies against human sequence of original TARA

reveal expression in sensory hair cells of the mouse inner ear and localization to the stereocilia.

62

Preimplantation Genetic Diagnosis for Single Gene Disorders and Chromosomal

Aneuploidy in Saudi Arabia

A Mohamad1, M Anwar1, H Kamel1, A A-Jalil1, S Qinawi1, M Mostafa1, A. Biricik2, F. Fiorentino2

1Dr. Samir Abbas Medical Centers and “GENITEC” Laboratories, Saudi Arabia; 2GENOMA Center,

Rome, Italy

Couples carrying a serious genetic disease that could pass to their offspring can benefit from

Preimplantation Genetic Diagnosis (PGD) technology. In Saudi Arabia, beta-thalassemia and sick-

le cell disease are so widespread that in some regions they can be defined as social diseases. PGD

for beta-thalassemia provides the opportunity to have a healthy baby that could also donate cord

blood stem cells to an affected sibbling if HLA is matching. In this report, the PGD experience of our

IVF and Genetics Center is described. Starting in 2005, 14 cycles for beta-thalassaemia and sickle

cell disease diagnosis with or without HLA matching have been performed for PGD on 125 embryo

biopsies with current three ongoing clinical pregnancies. Other 158 PGD cycles for couples with

high risk of chromosomal aneuploidy or embryo X/Y determination were also performed since 1999

with about 1000 embryo biopsies analyzed. Overall, PGD by PCR for single gene disorders and

FISH for chromosomal analysis was performed with a successful analytical rate of 98%. Results

were informative in 90% of the embryos. Selected embryos were transferred with overall pregnan-

cy rate of ~40% resulting in 70 clinical pregnancies and the birth of 61 babies. All pregnancies are

confirmed by prenatal genetic diagnosis. Our results establish the feasibility and the success of PGD

at our center.

63

DNA-Double Strand Break Repair Proteins and Viruses as

prognostic Indicators in Primary Nasopharyngeal Cancer

Smriti M. Krishna1,2, Dr. Susan James1, Dr. Prabha Balaram1

1Division of Cancer Research Regional Cancer Centre, Kerala, India; 2Molecular Biology &

Genetics Laboratory, Central Veterinary Research Laboratory, P.O. Box 597, Dubai,

United Arab Emirates

Genes mediating DNA repair plays an important role in the maintenance of genomic integrity and

recent reports shows a link between small DNA tumor viruses and DNA-repair pathways. Viral inter-

actions with tumor suppressor genes abrogate cell cycle arrest and disturb repair of therapy-induced

DNA-lesions. Nasopharyngeal carcinoma (NPC) is a unique cancer due to its etiology, and inci-

dence pattern and radiotherapy (RT) is the usual treatment modality. The biological aggressiveness

and the RT sensitivity of NPC lesions within the same stage, varies considerably and cannot be pre-

dicted by conventional histopathological evaluations. Hence there is a strong need for additional pre-

dictive and prognostic factors in order to improve therapy results of these patients. In the present

study the effect of EBV and HPV on DNA-repair proteins, ATM and DNA-PKcs was assessed in

NPC and benign nasopharyngeal epithelium. The rational of study was that evaluation of role of

viruses and expression of DNA-repair proteins in NPC might predict the clinical outcome, mainly

response to RT. Expression of DNA-PKcs and ATM were assessed by western blotting and protein

localization confirmed by immunohistochemistry, and presence of EBV and HPV by PCR using spe-

cific primers. 63% of NPC were EBV+ and 30% were HPV+. Expression of DNA-PKcs and ATM

were significantly increased in NPC when compared to benign samples (p=0.009). NPC showing

EBV infection resulted in reduction of expression of DNA-PKcs and ATM (p=0.011 & p=0.009). In

NPC’s with HPV infection, the mean expression values of the proteins were increased (p=0.003 &

p=0.001). NPC patients with HPV infection also showed significant lack of response to radiation

(p= 0.002). The study indicates that EBV infection down regulates the expression of DNA-repair

proteins and renders NPC sensitive to RT, whereas HPV infection up regulates expression of DNA

repair proteins making the tumors resistant to therapy. The results of the study also indicates that

assessment of expression of DNA-PKcs and ATM in biopsy specimens can be used as a criteria to

identify radio-resistant NPC’s and selection of appropriate therapy regimens.

64

Application of Molecular Cytogenomics Techniques in Research and Diagnosis

Vikram R. Jayanth1, A.M. George1, M. Li1, C. Fahey1, Y. Qi1, M. Schachowskoy1, Y. He1, M.

Shago2, S.W. Scherer1

1The Centre for Applied Genomics, 2Department of Pathology and Laboratory Medicine, Hospital

For Sick Children, MaRS Centre East Tower, 101 College Street, Toronto, Ontario, Canada M5G

1L7, Canada

Cytogenomics techniques have revolutionized and significantly increased the precision with which

we can map genes to chromosomes, characterize chromosome abnormalities and variation, and

perform genotype phenotype correlation in various disorders. The techniques used are karytoyping,

multicolor FISH, inversion analyses, fiber FISH, conventional and SKY karyotyping and comparative

genomic hybridization with microarrays (arrayCGH). We summarize the various services offered in

research and diagnostics at our Canadian based Centre, The Centre for Applied Genomics

(www.tcag.ca). We will illustrate the advantages and limitations of various molecular cytogenomics

techniques in different applications. Examples include the study of genetic anomalies occurring in

both human and mouse embryonic and adult stem cells, identification of copy number variants

(CNVs), validation of breakpoints in different human genome assemblies, G- to FISH mapping, and

identification of integration sites in transgenic lines. We are also actively involved in establishing cell

culture and biobanking services, genomic (eg. BAC, PAC) and cDNA (eg. MGC full-length) clone

distribution, fluorescent labeling of DNA probes and analysis using multicolor FISH, inversion test-

ing in interphase, and analysis of paraffin section and mitotic chromosomes. We also provide sup-

port for different diagnostic centers by supplying and labeling probes from our genomic library. Our

Centre is interested in expanding its facilities and sharing our expertise and resources with the Arab

world in addressing its unique needs in research and diagnosis.

65

Juvenile Hyaline Fibromatosis (Murray- Puretic- Drescher Syndrome):

Oral, Systemic and Histopathological Findings in an Egyptian Girl

Magda I. Ramzy1, Mona A. El-Gammal2

1Department of Orodental Genetics; 2Department of Clinical Genetics, Division of Human Genetics

and Genome Research

Juvenile hyaline fibromatosis (JHF) is an autosomal recessive condition that usually presents with

nodular/papular skin lesions and gingival hypertrophy during the first few years of life. There are

several conditions in which gingival fibromatosis is seen as the oral finding and can be correlated

with systemic or extraoral findings many of which have a genetic basis. This study describes clini-

cal, genetic, orodental and histopathologic changes in a girl with features of the rare juvenile hya-

line fibromatosis. Up to our knowledge, this is the first recorded case in Egypt. We will discuss the

major aspects of this syndrome and its differential diagnosis from other syndromes that may be

associated with hereditary gingival fibromatosis.

66

High Resolution HLA Typing Established in Dubai

Lawrence Torres, Rana Al Nouno, Abdul Rasheen Rahiman, Hans Meijer

Dubai Genetics FZ-LLC, United Arab Emirates

Many genomic diagnostic and research kits are based upon sequence information collected in US

and European laboratories. In a pilot study conducted by our genomics group, the discovery of new

alleles and SNPs in the well-characterized HLA loci indicates that the generation of sequence based

genotypes and allele frequencies is needed to validate to application of US and European diagnos-

tic kits in the Middle East and Asia. For high-resolution genotyping, Dubai Genetics developed

according to EFI standards the following high-throughput sequencing pipeline: (1) Barcode support-

ed sample receipt, (2) DNA extraction, QC and PCR setup on a Tecan RSP Genesis, (3) DNA purifi-

cation and sequence set-up on a 2nd Tecan RSP Genesis, (4) Sequence detection on an ABI 3100,

(5) Automated sequence processing and typing using AGENT, Assign, internal NCBI blast and

dbMHC. Ambiguous allele combinations are resolved through the sequencing of cloned PCR frag-

ments. Through automation of the cloning procedures on a QPExpression, allele separation and

sequencing is done within days. In the study one individual and 11 relatives were typed. Through

allele separation 8 digit unambiguous resolution was achieved. New alleles and intron SNPs were

discovered. The study demonstrates that high resolution typing of diagnostic quality is established

in Dubai and indicates that sequence based genotyping of Arab and Asian ethnicities will enrich

sequence space.

67

Perceptions Based on Religion in Medical Students on Stem Cell Research,

Cloning, and Preimplantation Diagnosis

Bugge Suryakantha, Neil George, Deepak Narayanan, Fariha Rabia

Universal Empire Institute of Medical Sciences, Knowledge village, Dubai, UAE

From the usage of cadavers, anesthetics, heart surgery, transplant surgery to gene therapy, the

medical fraternity was faced with opposition from sections of society from days bygone. After the

success of gene therapy on Asanthidesilva for SCID, molecular biologists and researchers faced

close scrutiny from regulatory bodies after the death of Jessy Gelsinger [OTC deficiency, a urea

cycle enzyme]. Even while gene therapy would transmit the vectors’ genome to the patient with

potential lethal effects, allogenic stem cells appeared a better alternative. Stem cells, cloning, and

preimplantation genetic diagnosis, and research in these areas continues fervently, but there appear

ethical and religious issues that need to be addressed. Medical college students in Dubai were

selected. The students were of different religious faiths, and were at different levels of understand-

ing of their faiths as most students elsewhere in the world. First and second year students of med-

ical college with problem-based learning were chosen because pathophysiology and treatment

modalities are actively learnt at this stage. The students were asked to independently answer ques-

tionnaire about their knowledge on stem cells and cloning, and their understanding of how their

belief system viewed these subjects. Preliminary data were interpreted; 50% of students whose

belief was Islam felt that their faith discouraged stem cell research. Since Today’s medical college

students metamorphosize into researchers, genetic counselors, and physicians, awareness of such

issues is highly appreciated.

68

69

AL HAYAT PHARMACEUTICALS

Established in 1982 as a Pharmaceuticals and medical Company, Al Hayat Pharmaceuticals is a

leading organization in the United Arab Emirates with branches in Dubai, Abu Dhabi and Ras Al

Khaimah representing leading International firms in Pharmaceuticals, Dental, Medical, Laboratory

Equipment and supplies. Al Hayat Pharmaceuticals also executes Hospital Turn-key projects.

Al Hayat Pharmaceuticals has established a molecular biology department in order to take care of

the increasing demand in the UAE and the region for molecular biology products in research and

diagnosis.

Major Companies Represented

• Invitrogen USA/EC - Molecular Biology Products

• Corbett Research, Australia - Real Time PCR Machine

• Roboscreen, Germany - Kits and Reagents For RT-PCR

• R-Biopharm, Germany - GMO and Food Testing By PCR

• Dynal, EC - HLA Typing and Dynabeads

Contact

AL Hayat Pharmaceuticals

Hamed Mohd. Abdullah Huraiz Bldg.

P.O. Box 4694

Al Garhoud - Dubai

United Arab Emirates

Tel: +971-4-268 3410

Fax: +971-4-262 3126

Email: [email protected]

Website: www.alhayatuae.com

70

BIOSCIENTIA

Founded in 1970, Bioscientia Institute for Medical Diagnostics is one of the largest purpose-built ref-

erence laboratories in Europe with in excess of 1000 professional, technical personnel. Since 1981

Bioscientia has been serving the Middle East as a reference laboratory – analyzing samples from

the major Military and Ministry of Health hospitals as well as private hospitals and clinics. The serv-

ice is the same to them all; quality results, fast and accurate reporting, interpretation as-sistance if

required and local offices to ease and lower the cost of communication. Since 1987, we have been

accredited by the “College of American Pathologists” (CAP) and participate in quality assurance pro-

grams on a national and international level.

Specimens are collected and shipped to Germany where they are processed. Bioscientia provides

all necessary packing materials, sample containers and personalized request forms.

Bioscientia Center for Human Genetics Ingelheim offers a complete program for medical genetic

diagnostics, including human genetic analyses, and tumor genetic diagnostics on solid tumors and

hematological diseases, as well as innovative DNA chip arrays for pharmacogenetics. The services

include genetic counseling, biochemical genetics, conventional and molecular cytogenetics, as well

as molecular genetics. Built up an in house group of experts, Bioscientia offers almost 500 molecu-

lar genetic analyses. Some one hundred of these tests are performed in Bioscientia’s laboratories;

other tests are offered in cooperation with national and international gene diagnostic networks,

including universities and other centers of excellence in the US, Canada and in Europe. The spec-

trum includes testing for common genetic diseases as well as some relatively rare genetic diseases

that are seldom performed by most laboratories.

Bioscientia follows and refers to the recommendations of the “Berufsverband Medizinische Genetik”

(The Board of Medical Genetics).

Contact

Bioscientia

Institute for Medical Diagnosis, Business Centre

Post Box No. 32014, Dubai, United Arab Emirates

Tel: +971-4-3974948, Fax: +971-4-3974129

71

GULF SCIENTIFIC CORPORATION

Gulf Scientific Corporation (GSC) is a specialized chemistry center supporting the fine products of

few international vendors across the Middle East.

Since its inception in 1990, GSC has been offering its customers innovative tools including applica-

tion and method development support, practical training courses and preventative maintenance

services. This was made possible with the creation of GSC's facility in Jebel Ali, which boasted cus-

tom-built training labs, a fully equipped service center and a spare parts depot. GSC has succeed-

ed in gaining the confidence of its principals and its customers and has grown to become one of the

unquestioned leaders. GSC is now run by a team of more than 82 professionals, and supported by

a network of distinguished local agents, with support offices in Saudi Arabia, Egypt, Kuwait, Iran,

Qatar, Yemen, Oman, Bahrain and Iraq.

Contact

Gulf Scientific Corporation (GSC)

P.O. Box 17010, Dubai, United Arab Emirates

Tel: +971-4-881-5270

Fax: +971-4-881-6778

Email: [email protected]

Corporate Mail: [email protected]

Website : www.gsc2000.com

Documents

H. E. Humaid Mohammad Obaid Al Qutami · 2008-10-21 · H. E. Humaid Mohammad Obaid Al Qutami Minister of Health, United Arab Emirates Chairman, Board of Trustees, Sheikh Hamdan Bin