Genetic Basis of Disease

(GBD)

Clinical Laboratory Science (CLS)

Module

Introduction & Classification

of Genetic disorders

Dr. Bassam Musa Sadik Moderator of GBD part of CLS

abmsadik@yahoo.com

Contents of this session:

• Definition of medical genetics

• What is Genetic Basis of Disease?

• What GBD is about?

• Why study GBD?

• Structure of GBD in CLS module

• Do we need to classify genetic diseases?

• What is different about genetic disorders?

• Summary

Objectives: By the end of this introductory sessions, the student should be able to: • Define medical genetics • Acknowledge the importance of genetic factors in

disease process • Value the impact of genetic disorders on health care • Classify genetic disorders • Appreciate the distinct features of genetic disorders

What is meant by Medical Genetics?

• Medical genetics is the specialty

of medicine that involves the diagnosis and

management of hereditary disorders, i.e. it refers

to the application of genetics to medical care.

• So, diagnosis, management, and counseling of

individuals with genetic disorders as well as

research on the causes and inheritance of genetic

disorders would be considered part of medical

genetics.

www.wikipedia.com

Various interrelated specialties within medical

genetics:

1. Clinical Genetics.

2. Cytogenetics.

3. Molecular Cytogenetics.

4. Molecular Genetics

5. Human genetics, molecular biology, genetic

engineering, or biotechnology.

What is Genetic Basis of Disease?

All human diseases in general, whether medical or surgical, can roughly be classified into three categories:

• Those that are genetically determined.

• Those that are almost entirely environmentally determined.

• And those to which both nature and nurture contribute.

Can you give example to each category?

Classification of diseases according to their etiology:

• Genetically determined

• Acquired

- inflammatory (trauma, burn)

- infective (tonsillitis, pneumonia)

- growth disorder (tumors, cancers)

- metabolic (DM)

- degenerative (OA)

- vascular (ischemia)

- drug induced (drug reactions, toxicity)

What Genetic Basis of Disease is about? 1. How genetic factors produce a disease 2. Inherited / hereditary / familial disorders 3. Birth defects, and 4. Much Mooooooore

Genetic diseases are not about children only …

• Every medical student should be aware of the impact of hereditary, genetic and other related disorders as they constitute a big burden on health care providers.

• Although not all of them are common, as some are rare, collectively they cause a great deal of morbidity and mortality as well as difficulty in diagnosis in many occasions.

• Doctors should effectively deal with cases having problems of probable / confirmed genetic origin.

BEFORE YOU START STUDYING GBD, PLEASE REVIEW YOUR HDTD & MBM in relation to:

1. Mitosis and meiosis including all steps and stages.

2. Protein structure, synthesis, types (enzymes, hormones, etc.) and their functions, etc.

3. Normal development from fertilization till birth (Review your embryology).

GBD in this curriculum consists of two parts: 1. Basic part, named GBD, in year II. 2. Clinical part , named clinical genetics, in a later year.

Faculty members: 1. Dr. Bassam Musa Sadik 2. Dr. Hedef Dhafir Al-Yasin 3. Dr. Shaymaa Jamal Ahmed 4. Dr. Manal Adnan Habeeb

LGT sessions = 22 SGT sessions = 10 (5x2) Lab. Visit = 2 (1x2)

1 Introduction Dr. Bassam

2 DNA structure + replication Dr. Hedef

3 Flow of genetic information (transcription + translation) Dr. Hedef

4 Post-translation modification + protein folding & targeting Dr. Hedef

5 Mendel's laws of inheritance + patterns (traits) of

inheritance

Dr. Shaymaa

6 Chromosomal abnormalities I Dr. Shaymaa

7 Chromosomal abnormalities II Dr. Shaymaa

SGL(I) = Example Down Syndrome

8 Single gene disorders + DNA mutations I Dr. Bassam

9 Single gene disorders + DNA mutations II Dr. Bassam

SGL(II) = Example PKU

10 Multifactorial disorders Dr. Shaymaa

SGL(III) = Example Neural tube defect

11 Disorders with atypical pattern of inheritance Dr. Shaymaa

12 Features of AD, AR, X-linked + Mitochondrial inheritance Dr. Bassam

13 DNA repair system Dr. Manal

14 Teratogenesis I Dr. Bassam

15 Teratogenesis II Dr. Bassam

16 Pharmacogenetics Dr. Bassam

17 Basis of genetic testing I Dr. Shaymaa

18 Basis of genetic testing II Dr. Manal

19 Genetic counseling Dr. Bassam

Lab visit (IV) = Instruments, devices used in genetic

testing

Library (V) = Eukaryotic DNA extraction (video)

20 Prevention of genetic disorders Dr. Bassam

21 Prenatala diagnosis Dr. Bassam

22 Ethical points in genetic / inherited disorders Dr. Bassam

SGL (VI) = Family pedigree analysis

References: 1. Elements of medical genetics. By Emery & Rimoin,

2010. 2. USMLE road map: Genetics. BY George H. Sack, 2008

(or later). 3. Robbins basic pathology, 2010. 4. Medical cytogenetics. By Hon Fong L. Mark, 2000. 5. An Introduction to Human Molecular Genetics:

Mechanisms of Inherited Diseases, Second Edition. By: Jack J. Pasternak, University of Waterloo, Ontario, Canada, 2005.

6. Other references & websites as referred to in place. 7. OR Just Google your keyword(s) and find out what

you'll get!! You'll find a lot of interesting information. I promise.

IN THIS PART, YOU ARE GOING TO STUDY THE FOLLOWING TOPICS:

• Introduction to genetic disorders • Genetic vs. acquired disorders • Significance of genetic disorders "statistics about incidence and

impact on health care providers“ • What makes genetic and inherited disorders different from

other disorders?

• Classification of genetic disorders. • Genetic factors causing a disease: A. Classical Group:

1.Chromosomal disorders + examples

2.DNA mutations + examples 3.Multifactorial disorders + examples

B. Non-classical genetic disorders.

• Features of AD, AR, X-linked (and mitochondrial inheritance) with their particular family pedigree.

• Teratogenesis & congenital malformation (birth defects) with clinically important examples.

• Prenatal diagnosis & Genetic counseling. • Basics of genetic testing (principles, indications, clinical

significance, and interpretation of results): 1.Chromosomal study, 2.In-situ hybridization and 3.Molecular study (PCR) and DNA-based tests

• Ethical points in genetics practice and research

Potential problems in clinical practice…

1. Mental retardation 2. Growth retardation 3. Abnormal sexual differentiation / genital ambiguity 4. Approach to a child with coarse features 5. Approach to a child with a major or minor malformation. 6. Antenatal care for mothers and unborn babies especially

for high risk group. 7. How to inform a family about their child with inherited

disorders

[Genetics is an integral part of all medical specialties]

Advances in molecular biology testing and their clinical applications [gene therapy, DNA recombination, stem cells, and modern diagnostics: real-time PCR (RT-PCR), microarray, comparative genomic hybridization (CGH), etc.]

Human diseases are either: 1. Genetically determined. 2. Or Almost entirely environmentally determined. 3. Or both nature and nurture contribute.

IS IT TRUE?

Microbial infections past and current views

Such disorders are far more frequent than is commonly appreciated (which represents only the tip of the iceberg).

• About 1% of all newborn infants possess a gross chromosomal abnormality.

• Approximately 5% of individuals under age 25 develop a serious disease with a significant genetic component.

• Around 20% of pediatric in-patients suffer from disorders of genetic origin.

• Up to 50% of spontaneous abortuses during 1st trimester chromosomal abnormality; in addition, numerous smaller detectable errors and many others still beyond our range of identification.

Only those mutations compatible with independent existence

constitute the reservoir of genetic diseases in the population.

Why it is important to study genetic diseases?

• 1/40 of all babies has a major malformation identifiable at

birth; in one half of them genetic factors can be implicated.

• Inherited disorders account for 50% of all cases of childhood

blindness and deafness;

• Together with congenital malformations, they are

responsible for 25-30% of all hospital admissions and deaths

occurring in pediatric age group.

• Relative contribution of genetics disorders to childhood

morbidity and mortality continue to rise as a result of

improvement in obstetrics, community pediatrics and

successful treatment of infections.

Do we need to classify genetic diseases?

Classification of Genetic disorders

I. Classical Genetic Diseases:

1. Chromosomal (Cytogenetic) abnormality disorders.

2. Single gene (or unifactorial or Mendelian)

Disorders.

3. Multifactorial disorders.

II. Non-Classical Diseases "or single gene disorders with atypical

pattern of inheritance":

a. Diseases caused by mutations in mitochondrial genes.

b. Triplet repeat mutations.

c. Uniparental disomy / Genomic imprinting.

d. Gonadal mosaism.

Added to that, is a large group of disorders "malformations"

that manifest at birth, called congenital malformations (Birth

Defects), that many of them are caused by genetic disorders.

What makes genetic disorders distinct from other disorders? 1. Runs in families 2. Tendency to recurrence 3. Non-affected individuals could carry the abnormality

themselves 4. Probability of occurrence calculations of risk 5. Diagnosis on solid basis is necessary 6. Geographic & ethnic variation in distribution of diseases 7. HX includes family Hx 8. Physical examination includes examination of other family

members. 9. Attention to details is important 10. Much moooore

Genetic factors can lead to genetically determined disorders

(inherited / hereditary / familial)

and Play a significant role in the so called

multifactorial disorders

and A variable role in “non-genetic” disorders

Summary: • Genetic disorders represent a huge burden on health

care providers. • It is of utmost importance for medical students to

understand the role of genetic factors in disease process.

• Understanding each factor and how it causes a disease is important.

• Genetic disorders have unique characteristics than other non-genetic diseases.

• You learn not only by reading lectures in teaching halls ….

Any Question?

THANK YOU