GeneticsGenetics

Islamic UniversityIslamic University

College of NursingCollege of Nursing

IntroductionIntroduction

Our understanding of human genetics improved in the Our understanding of human genetics improved in the

few past years.few past years.

This was occurred after the discovery of the gene This was occurred after the discovery of the gene

map.map.

Human diseases and the different disorders are Human diseases and the different disorders are

influenced by both influenced by both environmentalenvironmental and and geneticgenetic

factors with varying degrees, for example, factors with varying degrees, for example, DownDown

syndromesyndrome is pure genetic disease, is pure genetic disease, ScurvyScurvy is pure is pure

due to environmental factors. In between combined due to environmental factors. In between combined

such as DM, HTN (Multi-factorial). such as DM, HTN (Multi-factorial).

Human CellHuman Cell Normal human cell contains 46 (23 pairs) Normal human cell contains 46 (23 pairs)

chromosomes, 22 pair autosomes and the chromosomes, 22 pair autosomes and the

23rd chromosome is sex pair.23rd chromosome is sex pair.

XXXX for the female and for the female and XY XY for the male.for the male.

Approximately 50,000 genes encoded in the Approximately 50,000 genes encoded in the

human DNA. (Deoxyriboneuclic Acid) human DNA. (Deoxyriboneuclic Acid)

46

46

23

23

23

23

23

23

23

23

23 23

23

23

23

23

Mitosis

Meiosis I

Meiosis II

Cell Division

Spermatogenesis & OogenesisSpermatogenesis & Oogenesis

Gametogenesis in male and female are Gametogenesis in male and female are

principally the same but differ in timing of the principally the same but differ in timing of the

various stages.various stages.

Spermatogenesis begin in the seminefrous Spermatogenesis begin in the seminefrous

tubules around the puberty & continue out life.tubules around the puberty & continue out life.

Oogenesis begin in the intrauterine life but is Oogenesis begin in the intrauterine life but is

arrested in meiosis I, with completion of the arrested in meiosis I, with completion of the

cycle when ovulation occurs and continue up to cycle when ovulation occurs and continue up to

50 years old. 50 years old.

Sexual Division of Ova and sperm

46

4623

23

23

23

Ova

Sperm

Meiosis I

Meiosis II

Normal

Polar body

Abnormal

Polar body

Abnormal

Normal

Not contain cytoplasm

Not contain

cytoplasm

Not contain cytoplasm

Duplication of genetic Duplication of genetic materialsmaterials

ABCDEF

A

B

C

D

E

F

Short arm (P)

Long arm (q)

Centromere

Male chromosomes Female Chromosomes

Th

e

Sam

e

Proteins

Preparation for genetic Preparation for genetic studystudy

1- 1- Separation of WBCs by centrifugation.Separation of WBCs by centrifugation.

2- Cultivate the lymphocytes by adding 2- Cultivate the lymphocytes by adding

phytohemagglutinin.phytohemagglutinin.

3- Arrest cell division after about 70 hours by adding 3- Arrest cell division after about 70 hours by adding

colchicines to the culture.colchicines to the culture.

4- Release the chromosomes from the nucleus by 4- Release the chromosomes from the nucleus by

adding hypotonic saline.adding hypotonic saline.

5- Fix and stain. 5- Fix and stain.

Indications for chromosomal studiesIndications for chromosomal studies

1.1. Mental retardation.Mental retardation.

2.2. Multiple congenital abnormalities.Multiple congenital abnormalities.

3.3. Recurrent abortion.Recurrent abortion.

4.4. Infertility.Infertility.

5.5. Ambiguous sex.Ambiguous sex.

6.6. Leukemia.Leukemia.

7.7. Failure to thrive child.Failure to thrive child.

8.8. Some syndromes. (turner). Some syndromes. (turner).

DefinitionsDefinitions:: Gene:Gene: describe the hereditary factor that describe the hereditary factor that

determine the trait or disorder.determine the trait or disorder.

Locus:Locus: is the position at which the is the position at which the

structural gene lies. Individuals have 2 structural gene lies. Individuals have 2

alleles at each locus. alleles at each locus.

Homozygous:Homozygous: if the if the 2 alleles2 alleles at a at a singlesingle

locuslocus are are identicalidentical. (. (RecessiveRecessive))

Definitions Definitions contcont……

Heterozygous:Heterozygous: if the if the 2 alleles2 alleles in a in a

singlesingle locuslocus are are differentdifferent. (. (DominantDominant) )

DominantDominant: if the condition is manifest with : if the condition is manifest with

singlesingle gene, example heterozygous state. gene, example heterozygous state.

RecessiveRecessive: if the condition is seen only in : if the condition is seen only in

the homozygous state. Occurred when the the homozygous state. Occurred when the

two alleles are abnormal.two alleles are abnormal.

Autosomal RecessiveAutosomal Recessive RecessiveRecessive: the condition is seen only in the : the condition is seen only in the

homozygous state. (identical)homozygous state. (identical)

Occurred when the Occurred when the twotwo alleles are alleles are abnormalabnormal..

The disorder is more common among The disorder is more common among

consangeous marriage. Siblings have one half of consangeous marriage. Siblings have one half of

their genes in common, where first cousins have their genes in common, where first cousins have

one-eight of their genes in common.one-eight of their genes in common.

One third of inherited traits are AR. One third of inherited traits are AR.

Criteria of AR disordersCriteria of AR disorders1.1. Parents are usually healthy.Parents are usually healthy.

2.2. Affected individuals are almost the offspring of Affected individuals are almost the offspring of

heterozygot carrier parents.heterozygot carrier parents.

3.3. Percent % to be affected of children if the Percent % to be affected of children if the

parents are carriers is 1:4.parents are carriers is 1:4.

4.4. If both parents are affected all children will be If both parents are affected all children will be

affected. affected.

5.5. Both sexes are affected equally.Both sexes are affected equally.

6.6. It causes mainly It causes mainly enzymeenzyme deficiency. deficiency.

7.7. Example: Cystic Fibrosis, Galactosomia, Example: Cystic Fibrosis, Galactosomia, Phenlketonurea, Thalassemia, and others.Phenlketonurea, Thalassemia, and others.

Autosomal Dominant (AD)Autosomal Dominant (AD)

Dominant means that the disease allele or Dominant means that the disease allele or

gene need to be present only in single copy gene need to be present only in single copy

(heterozygot) to result in phenotype.(heterozygot) to result in phenotype.

The affected individuals posses both the The affected individuals posses both the

abnormalabnormal and and normalnormal gene. gene.

More than half of the inherited traits are More than half of the inherited traits are

autosomal dominant. autosomal dominant.

Criteria of Autosomal (AD) Criteria of Autosomal (AD) disorderdisorder

Disease is transmitted from generation to Disease is transmitted from generation to

generation and can be tracked to several generation and can be tracked to several

generations.generations.

Sporadic cases can occur due to new mutations, Sporadic cases can occur due to new mutations,

it occur more frequently in sever cases in which it occur more frequently in sever cases in which

the chance of survival or reproduction of the the chance of survival or reproduction of the

affected persons are low.affected persons are low.

It affect both sexes equally.It affect both sexes equally.

Criteria of Autosomal (AD) Criteria of Autosomal (AD) disorderdisorder

The risk of transmission to the offspring is The risk of transmission to the offspring is

50% they show variability in severity.50% they show variability in severity.

AnticipationAnticipation: The severity of the disease : The severity of the disease

tended to increase with each generation.tended to increase with each generation.

An example: Myotonic dystrophy, the An example: Myotonic dystrophy, the

grandfather could have cataract only, the grandfather could have cataract only, the

mother had myotonia and muscle weakness mother had myotonia and muscle weakness

and the affected child had congenital and the affected child had congenital

myotonic dystrophy with developmental myotonic dystrophy with developmental

delay.delay.

Example of ADExample of AD AchondroplasiaAchondroplasia. . (disease of bone growth cause short (disease of bone growth cause short

structure M. 131, F124, not able to convert cartilage into structure M. 131, F124, not able to convert cartilage into

long bone)long bone)..

Neurofibromatosis. Neurofibromatosis. (NF1)causes skin changes and (NF1)causes skin changes and

deformed bones. It usually starts in childhood. Sometimes deformed bones. It usually starts in childhood. Sometimes

the symptoms are present at birth. (NF2) causes hearingthe symptoms are present at birth. (NF2) causes hearing

loss, ringing in the ears, and poor balance. Symptoms often loss, ringing in the ears, and poor balance. Symptoms often

start in the teen years.start in the teen years.

Example of ADExample of AD

Polycystic Kidney disease. Polycystic Kidney disease. (ADPKD) is a multi-systemic (ADPKD) is a multi-systemic

and progressive disorder characterized by cyst formation and and progressive disorder characterized by cyst formation and

enlargement in the kidney and other organs (eg, liver, pancreas, enlargement in the kidney and other organs (eg, liver, pancreas,

spleen). Up to 50% of patients with ADPKD require renal replacement spleen). Up to 50% of patients with ADPKD require renal replacement

therapy by 60 years of age.therapy by 60 years of age.

Retinoblastoma.  Retinoblastoma.  (is the most common primary ocular (is the most common primary ocular

malignancy of childhood).malignancy of childhood).

Spherocytosis.  Spherocytosis.  is a familial hemolytic disorder with marked is a familial hemolytic disorder with marked

heterogeneity of clinical features, ranging from an asymptomatic heterogeneity of clinical features, ranging from an asymptomatic

condition to fulminant hemolytic anemiacondition to fulminant hemolytic anemia

X-linked diseasesX-linked diseases

Transmitted by heterozygous mother to Transmitted by heterozygous mother to sonssons

Daughters - 50% carriers, 50% healthyDaughters - 50% carriers, 50% healthy Sons - 50% diseased, 50% healthySons - 50% diseased, 50% healthy Children of diseased father - sons are Children of diseased father - sons are

healthy, all daughters are carriershealthy, all daughters are carriers Hemophilia AHemophilia A (defect of Factor VIII)(defect of Factor VIII) Hemophilia BHemophilia B (defect of Factor IX)(defect of Factor IX) Muscle dystrophyMuscle dystrophy (Duchen disease)(Duchen disease)

Autosomal disordersAutosomal disorders

Trisomy 21 (Down syndrome)Trisomy 21 (Down syndrome)

Most frequent - 1:700 births; parents have Most frequent - 1:700 births; parents have

normal karyo-type.normal karyo-type.

Maternal age has a strong influence: <20 y. Maternal age has a strong influence: <20 y.

1:1550 live births, >45 y. 1:25 live births1:1550 live births, >45 y. 1:25 live births

Most frequently is abnormality in ovum (ovum Most frequently is abnormality in ovum (ovum

is under long-time influence of environment)is under long-time influence of environment)

HEREDITYHEREDITY The passing of traits from parent to offspring. The passing of traits from parent to offspring.

ALLELE ALLELE The different forms of a trait that a gene may The different forms of a trait that a gene may

have. One form of a genehave. One form of a gene

GENOTYPEGENOTYPE

An organism's genetic makeup.An organism's genetic makeup.

PHENOTYPE PHENOTYPE

Outward physical appearance and behavior of an Outward physical appearance and behavior of an

organism. organism.

TRAITTRAIT Ways of looking, thinking, or being. Traits that are Ways of looking, thinking, or being. Traits that are

genetic are passed down through the genes from parents genetic are passed down through the genes from parents

to offspring.to offspring.

Autosomal DominantAutosomal Dominant

Autosomal RecessiveAutosomal Recessive

Autosomal RecessiveAutosomal Recessive

Sex linked diseaseSex linked disease