1 Genetic Apparatus Eng

8/8/2019 1 Genetic Apparatus Eng

1/12

01.02.200

Humangenetics

2

Human genetics

Lectures - 17x2;

Seminars17x3;

2 concluding tests

4 mandatory testsFinal examination (tests + practical part)

3

Agricultural revolution XVII-XVIII century

Industrial revolution XIX century

Informational revolution XX century

Genetic revolution XXI century


2/12

01.02.200

4

Developmentof Human and Medical genetics

1956 identif ication of number of humanchromosomes (46,XX; 46,XY);

1961- relationship between chromosomalaberrations and human diseases;

1966 decoding of genetic code, description ofinherited metabolic diseases; prenatal diagnosisvia amniocentesis.

1980 cloning of f irst human gene.

5

1981 - molecular methods used for location of genes inchromosomes.

1985 - PCR used for identification of mutations.

1991 clonin g of genes inv olved in many human diseases:Dush enne muscle distrop hy, cysti c fibrosis,neurofibromatos is, reti nita pigmentosum, Marfan sdr.

6

1994 McKusick published MendelianInheritance in Man; A Catalog of Human Genesand Genetic Disorders.

1996 preimplantation diagnostic of embryosobtained by in vitro fertilisation.

1996 - 2001 more then 1000 genes involved inhuman pathology were described.


3/12

01.02.200

7

In 2001 Human genome project starts.Dur ing 2001 -2003 many visions were changed:

From structure to function of genes;

From location of genes in chromosomes to sequencing ofDNA;

From diagnost ic of genetic di seases to calculation ofpredisposition to genetic diseases;

From etiology to mechanisms;

From analysis of monogenic traits to analy sis ofpolygenic traits;

From genome to proteome;

From medical genetics to genetic medicine;

8

Organism

Cell

Nucleus

Chromosomes

DNAAmino acidsProtein

9

PatientWhat to do for

solving o f this

problem?

What is the

problem?

CLASSIC VISION GENETIC VISION

What is prognostic and

prophylaxis of co nsequences

of diseases in patient?

What is the risk for this

disease for other members of

the family?

Why this patient has this

disease now?

What possibilities are for

prevention or reducing of

effect disease for patient

or/and its family?


4/12

01.02.200

10

Human genetics

Fundamental and applicative science

Genetics is fundamental science because study:

structure,main mechanisms,

lows,

- Which ensure keeping, transmission and expression of

human traits,

- Ensure formation, development and functions of

human organism.

11

Genetics is a clinic scienceWhich study relationships between heredity and diseases:

- mutations (monogenic, polygenic or chrs) determine

* a disease or

* a predisposition for a genetic disease.

- Genetic diseases are:

* numerous -9000;

* frequent - 5-8% in newborns.

- Genetic diseases are present in all medical fields.

12

What genetics

gives to

contemporaneous

doctors?

New methods ofdiagnostic

New e tio-pathologicaldrugs

Gene therapy

Cell therapy

Prenatal diagnostic

Preimplantativdiagnostic

Family planning

Understanding ofEtio-pathology

Prognosis of diseaseevolution


5/12

01.02.200

13

Lymphocytes 374

Endothelial cells 1031

Salivary g lands 17

Thyroid gland 584

Parathyroid gland s 46

Smooth muscle 127

Mammal glands 69 6

Pancreas 1094

Spleen 1094

Adrenal glands 658

Gallbladder 78 8

Small intestine 29 7

Placenta 1290

Skeletal muscle 73 5

Prostate 1283

Leucocytes 2164

Brain 3195 genes

Eye 547 genes

Bons 904 genes

Adipose tissue 581 genes

Thymus 261 genes

Esophagus 76 genes

Lungs 1887genes

Heart 1195 genes

Liver 2091 genes

Erythrocyte 8 genes

Trombocytes 22 genes

Large intestine 874 genes

Kidney 712 genes

Testis 370 genes

Ovary 504 genes

Uterus 1859 genes

Embryo 1989 genes

Skin 62 0 Synov ial membrane 813 genes

Genes involved in humandevelopment and functions of

tissues and organs

14

All pathologies have a geneticcomponent

Mutations (modifications of genetic material) Responsible for a disease / syndrome

Responsible for p redisposition to a disease

Change resistance against infectious agents

Change the metabolism o f drugs

Influence the regeneration of tissues

Etc.

15

Genetic diseases are numerous.

There are knownover10.000of disease de termined or c onditioned by geneticfactors.

Are highly diverse.

May appear atany age.

May affectany organ present in all fields of medicine.

Present in5-8% of newborns.

Genetic factors may be responsible for reproductive disorders (sterility,miscarriage).

Genetic diseases responsible for infantile mortality and morbidity.

Genetic diseases are chronic diseases and produce physical or mentaldisorders.


6/12

01.02.200

16

Geneticdiseases

Types Examples

Chromosomalsyndromes

> 1000

Aneuploidies47, XX, +21 (Down sdr.);47, XXY (Klinefelter sdr.);45,X (Turner sdr.);

Chromosomalaberrations

Del, dup, izo, r;

ex: cri du chat sdr.; Wolf-Hirschhorn sdr.; DiGeorge sdr.;Williamssdr.

Monogenicdiseases

> 9000

Autosomaldominante

FH, ADPKD, neurofibromatosis 1, Marfan sdr., Huntingtondisease, breast cancer, colon cancer

Autosomalrecesive

Phenylketonuria, chiytic fibrosis, sickle cell anemia,albinism

X-linkedHemophi lia, muscle dystrophy, color blindness

MitochondrialLebern europathy

Polygenicdiseases

> 100

Adult diseasesDiabetes, hypertension, obesity, cancers

Isolatedmalformationsin children

Defects of neural tube, cleft lips, heart congenitalmalformations

17

Frequency of genetic diseases

0,70%

2%

10%

0, 00% 2, 00% 4, 00% 6, 00% 8, 00% 10, 00%

Chromosomal

sdr.

Monogenic

diseases

Polygenic

diseases

18

Human genetics

Medical genetics

Clinical genetics

The direction in human genetics which study genetic diseases is

called medical genetics.

Clinical genetics is a part of medical genetics.


7/12

01.02.200

19

Genetics is a science which study:

- heredity and

- variability of human organism.

Substrate of heredity and variability:

Molecular

DNA

Morphologic

Chromosomes

Cellular

Genetic

apparatus

20

Genetic apparatus of human cells

Genetic material:

a) 46 mol. Nuclear DNA;

b) 2-10 mol. mtDNA

Cell components ensure:

Realization of GI

a) Transcription

apparatus;

b) Translationapparatus

!!! RIBOSOMES

Transmission of G I

a) Replication

apparatus;

b) Mitoticapparatus

!!! CENTRIOLS

Nucleus

Mitochondria

Ribosomes

Centriols

21

Levels of organization of genetic material

I. Genome complement of cell DNA

(nuclear + mitochondrial)II. Chromosome a linkage group of genes

III.Gene elementary unit responsible for

synthesis of a protein and expression of a

trait


8/12

01.02.200

22

Peculiarities of human genome

Haploid nuclear genome

3,2 x 109 p.b.

~ 30000 genes

Mitochondrial genome

16,6 kb

37 genes

Gene DNA

25%

Extragenic DNA

75%

CodingDNA10%

NoncodingDNA90%

Single and low

copy sequences

60%

Moderate andhighly r epetitive

sequences

40%

23

Chromosome 1 2 3 4 5 6 7 8

No. of genes 2782 1888 1469 1154 1268 1505 1452 984

Length, Mb 247 243 200 191 180 171 159 146

Chromosome 9 10 11 12 13 14 15 16

No. of genes 1148 1106 1848 1370 551 1276 945 1109

Length, Mb 140 135 134 132 114 106 100 89

Chromosome 17 18 19 20 21 22 X Y

No. of genes 1469 432 1695 737 352 742 1336 307

Length, Mb 79 76 64 62 46,9 50 155 58

24

Obligatory elements Facultative elements

Structural genes;

tRNA, rRNA genes;

Palindroms;

SatelliteDNA

Mobile elements

Pseudogenes

Foreign DNA


9/12

01.02.200

25

Non-coding sequences of human genome

SINEs transposones, initiation of replication

LINEs retrotransposone s, conjugation of chromosomes

during meiosis I

Minisatellite DNA markers of chromosomes

Satellite DNA structural role, constitutive

heterocrhromatin (c, t, h, s)

Microsatellite DNA individual genetic markers

LINEs (Long interspersed elements) 16%

SINEs (Short interspersed elements) 11%

26

Human chromosomes

dynamic structures with different shape, level of condensation,

gene activity:

single-chromatid or two-chromatid;

chromatin or chromosome;

transcriptional active or inactive.

morphologic s ubstrate of H and V;

supramolecular level of organization of genetic material (DNA +

histones + non-histones + RNA)

27

self-reproduction of chromosomes takes place during S phase

of interphase (replication).

chromosomes represent linkage groups of genes:

- each chrs contains a specific number of genes;

- each gene has a specific place in chrs - locus;

- genes of one chromosome are inherited together

a diploid set of chromosomes is called karyotype:

23 pairs: 22 pairs of autosomes +

1 pair of gonosomes (XX or XY).

Pair of chromosomes = homolougus chromosomes


10/12

01.02.200

28

Origin of gonosomes

29

landmarks of karyotype:

relative and absolute length of chrs,

position of ce ntromere = primary constriction - c,

presence of s econdary constrictions - h,

presence of s atellites - s

chromosomes may be analyzed during:

metaphase (homogenous painting or banding)

prometaphase (banding)

interphase (hybridization with fluorescent probes)

30

chromosomes have heterogeneous structure:

- Coding and non-coding sequence s;

- euchromatin and heterochromatin,

- single copy and repetitive sequen ce;

-GC and AT reach sequences;

- transcribed and non-transcribed sequences ;

- sequence s associated with basic and basic proteins .

!!! This explains origin of chromosomal bands

Chromosomal number and structural abnormalities induce

developmental abnormalities - sundromes


11/12

01.02.200

31

The shape of chromosome depends on position of

centromere

Structure of metaphase chromosomes.

Rchromosomal landmarks

Secondary

constriction

Satellite

Centromere Primary

constriction

Sister

chromatids

32

100xqp

pIc

33

Human karyotype


12/12

01.02.200

34

Classification of chromosomes

By length:

-Large

-Medium

-Small

By shape:

-Metacentric

-Submetacentric

-Acrocentric

By type:

-Autosomes

-Gonosomes

By presence of

other lendmarks:

-h on p arm

-h on q arm

-satellites

Grupes:

A 1-3

B 4,5

C X, 6-12

D 13-15

E 16-18

F 19,20

G 21, 22, Y

35

Human karyotype and chromosomal

formula

46,XX

46,XY

47,XXY

45,X

47,XY,+21

45,XY,-21

46,XX,5p-

Documents

1 Genetic Apparatus Eng