Human genetics

Dr : Kawkab Adris Mahmood Lecturer / Microbiology College of Medicine Department of Anatomy

* * Human Genetics

Human genetics : is the study of inheritance as it occurs in human beings .

* * Human body consist of trillions of cells each cell nucleus has 46 chromosomes

Human genome : consist of 46 chromosomes arranged in 23 pairs located in the nucleus of each cell and the chromosome consist of genes that consist of DNA

Chromosome: The structure by which hereditary information is transmitted from one generation to the next. Located in the nucleus, it is consists of tightly coiled thread of DNA with associated proteins and RNA. The genes are arranged in linear order along the DNA .

Gene : is a certain segment of DNA that contains the necessary code to make RNA or polypeptide ( proteins ) . Allele : An alternate forms of a gene that occur at agivin locus in chromosome .

In a karyotype, chromosomes are arranged and numbered by size, banding pattern and centromere position from largest to smallest. This arrangement helps scientists quickly identify chromosomal alterations that may result in a genetic disorder.

Karyotype : is a test to examine chromosomes in a sample of body cells, which can help identify genetic disease. This test can: Count the number of chromosomes Look for structural changes in chromosomes
Karyotype : picture of the chromosomes in the nucleus of the cell used to check for abnormalities .
Karyotype Test :


Clinical Indication for Chromosome Analysis :
The amniotic fluid test is done to check a developing baby for chromosome problems . Fertility problems, on a couple that has a history of miscarriage . To examine any child or baby who has unusual features or developing delays. Sex determination ( Ambiguous genitalia ) Molecular diagnosis of cancer

* * Preparation of Karyotype : 1- Sample Collection : A - Prenatal Diagnosis : During pregnancy the sample can either be :
B - Postnatal Diagnosis :

Amniotic fluid collected during an amniocentesis

A piece of the placenta collected during a chorionic villi sampling test ( CVS )
Blood sample
Bone marrow


2 - Growing Cells : In order to have enough cells to analyze , the dividing cells are grown in special media or a cell culture . This media contains Phytohaemagglutinin that enable the cells to divide and multiply

3- Culturing cells can take 3 to 4 days for blood cells and up to a week for fetal cells . 4- Cell Division is arrested at Metaphase by the addition of colchicine ( prevents mitotic spindle fibers forming ) . 5- Hypotonic solution is added to cause the cells to swell and to separate the individual chromosome before fixation . 6 - Staining the Chromosomes : Giemsa dye G-banding ( Giemsa banding )

Preparation of Karyotype

7 - Analysis of Chromosomes :



There are 46 chromosomes that can be grouped as 22 matching pairs and 1 pair of sex chromosomes (XX for a female and XY for a male). The size, shape, and structure are normal for each chromosome.
Normal Human Karyotype:
There are more than or less than 46 chromosomes. The shape or size of one or more chromosomes is abnormal. A chromosome pair may be broken or incorrectly separated.
Abnormal:
The Result of Karyotype Test :
Normal female karyotype 46,XX

Classification of Chromosomes according to the Position of Centromere :

* * the chromosomes are numbered 1 to 22 from longest to shortest. The last pair are the sex chromosomes and are placed on the karyotype after the 22nd pair. The chromosomes can be separated into groups, based on their length and the position of the centromere.
Human Chromosome Groups

* * Human Chromosomes

Cell nucleus
Normal human male karyotype

Application of Karyotype : Diagnosis of genetic disease and classification of genetic disease because its used to detect :A– Abnormalities in chromosome number B– Abnormalities in chromosome structure.C- Molecular diagnosis of cancer .


A- Abnormalities in chromosome number :

Abnormalities in chromosome number resulted from nondisjunction nondisjunction a chromosome pair fails to separate at anaphase of either the first or second meiotic division . This produces a sperm or oocyte that has two copies of a particular chromosome, or none, rather than the normal one copy . When such a gamete fuses with its partner at fertilization the zygote has either 45 or 47 chromosomes instead of the normal 46 .

Nondisjunction of chromosomes in meiosis and fertilization

Nondisjunction and Sex Chromosomes
Nondisjunction and autosome Chromosomes

Down Syndrome:

1 in 1,250 births 47 chromosomesXY or XX #21 Trisomy Nondisjunction
Short, broad hands Stubby fingers Rough skin Impotency in males Mentally retarded Small round face Protruding tongue Short lifespan

1 in 14,000 births 47 chromosomesXY or XX #13 Trisomy Nondisjunction

Small head Small or missing eyes Heart defects Extra fingers Abnormal genitalia Mentally retarded Cleft palate Most die a few weeks after birth
Patau’s Trisomy Syndrome

Edwards Syndrome ( Trisomy 18 ) : Symptoms include fingers overlapping , average survival time is 4 months with death usually caused by pneumonia or heart failure . Trisomy for chromosome 18


Turners Syndrome
1 in 5,000 births 45 chromosomes X only #23 MonosomyNondisjunction
96-98% do not survive to birth No menstruation No breast development Narrow hips Broad shoulders and neck

Klinefelter Syndrome

1 in 1,100 births 47 chromosomesXXY only #23 Trisomy Nondisjunction
Scarce beard Longer fingers and arms Sterile Delicate skin Low mental ability Normal lifespan

Triple X Syndrome

Normal physically Sometimes taller Normal mentally Inc. risk of retardation Fertile
1 in 1,ooo females 47 chromosomes , XXX Triplo X females

Polyploidy : A cell with extra sets of chromosomes . The total number of chromosomes 69 chromosomes . The causes is error in cell division ( meiosis or mitosis ) and multiple fertilization Triploidy detected at amniocentesis 3 copies of each chromosome in every cell lead to spontaneous abortions and stillbirths and newborn deaths .

B- Abnormality in Chromosome Structure : Structural abnormalities results from chromosomal breakage and abnormal reunion . 1- Deletion 2- Duplication 3- Inversion 4- Translocation 5- Ring chromosome

Cri-Du-Chat Syndrome

1 in 216,000 births 46 chromosomes Deletion of shortarm of chromosome 5
Symptoms: Moon-shaped face Heart disease Mentally retarded Malformed larynx Normal lifespan


4 - Translocation : the transfer of a segment of one chromosome to another chromosome . Examples of cancers associated with Translocation : 1- Chronic Myelogenous Leukemia 2- Burkitts Lymphoma
Abnormalities in Chromosome Structure

In Chronic Myelogenous Leukemia a reciprocal translocation between chromosome 9 and chromosome 22 forming Philadelphia chromosome It results in one chromosome 9 longer than normal and one chromosome 22 shorter than normal , the latter is called the Philadelphia chromosome This translocation is designated t ( 9 ; 22 )
Chronic Myelogenous Leukemia
Philadelphia Chromosome

Philadelphia chromosome

The diagnostic Karyotype abnormality for Chronic Myelogenous Leukemia shows reciprocal translocation t ( 9 : 22 )

In most (approximately 90%) of the cases of Burkitt's lymphoma, a reciprocal translocation between chromosome 8 and chromosome 14 This translocation is designated t ( 8 ; 14 ) leading to abnormal growth of lymphoid tissue and development of Burkitts lymphoma .
Burkitt Lymphoma


Here is an actual karyotype of a cell from the tumor of a patient with Burkitt's lymphoma. The long (q) arm of the resulting chromosome 8 is shorter (8q−) than its normal homologue; the long arm of translocated chromosome 14 longer (14q+).

Breast Cancer

Karyotype of breast cancer cell showing translocations, deletions , and aneuploidy characteristic features of cancer cells .
Several chromosomal changes ; abnormalities in chromosome number and structure .



5 - Ring chromosome : A chromosome loses telomeres and the ends fuse forming a circle . Mechanism of ring chromosome :

Human Karyotype from bladder carcinoma showing ring chromosome in addition to other chromosomal abnormalities .

* Abnormal numbers or sizes of chromosomes can lead to many genetic disorders , some are shown in this table , these disorders can be revealed by karyotype analysis .
Abstract

Blood Groups : Types of Blood groups :

1- Blood group A : Individuals have A antigen on the surface of their red blood cells ( RBCs ). 2- Blood group B : Individuals have B antigen on the surface of their RBCs . 3- Blood group AB : Individuals have both A and B antigens on the surface of their RBCs . 4- Blood group O : Individuals do not have either A or B antigens on the surface of their RBCs . RH System : Individuals have RH ( D ) antigen on the surface of their RBCs .

RH- System

Inheritance of Blood groups :
Blood groups are inherited from both parents . ABO blood types is controlled by a single gene called I . it has 3 alleles IA , IB , IO . The gene is located on chromosome 9 . This gene responsible for the producing of the A and B antigens .

Table : Genotypes and the Corresponding Phenotypes ( Blood Group Types ) for the ABO Locus in Humans .
Frequency in Population
Phenotype
Activity
Genotype
42%
A
α-3-N-acetyI-D-galactosaminyltransferase IA IA, IA IO
8%
B
α-3-D-galactocyltransferase IB IB, IB IO
3%
AB
Both enzymes
IA IB
47%
O
None
IO IO


For Example : The blood group of the father is A , and the blood group of the mother is O , Give the possible genotypes and blood groups of the children . 1- IA IA Ч IO IO → IA IO IA IO 2- IA IO Ч IO IO → IA IO IO IO The blood group of the children either A or O as in table 2

Inheritance of Blood Types

These charts show the possible blood type results for offspring.
Mothers's Type
Blood Type
AB
B
A
O
A, B
O, B
O, A
O
O
Fathers' Type
A, B, AB
O, A, B, AB
O, A
O, A
A
A, B, AB
O, B
O, A, B, AB
O, B
B
A, B, AB
A, B, AB
A, B, AB
A, B
AB
Mother's Type
Rh Factor
Rh -
Rh +
Rh +, Rh -
Rh +, Rh +
Rh +
Father's Type
Rh -
Rh +, Rh -
Rh -

Inheritance of Blood Types

Inheritance of ABO and RH blood groups :


Example 1 : The blood group of the mother A+ and the blood group of the father O- Give the possible genotypes and blood groups of the children .
A+ could be : AA++ or AA+- or AO++ or AO+-
A+
A+
AO+-
AO+-
O-
The blood group of the children : 100% A+
A-
A+
AO--
AO+-
O-
The blood group of the children : 50% A+ or A-
O+
A+
OO+-
AO+-
O-
The blood group of the children : 50% A+ or O+
O-
O+
A-
A+
OO--
OO+-
AO--
AO+-
O-
The blood group of the children : 25% A+ or A- or O+ or O-


Example 2 : The blood group of the mother O- and the blood group of the father O- Give the possible genotypes and blood groups of the children The blood group of all children 100% O-

Example 3 : The blood group of the mother O- and the blood group of the father O+ Give the possible genotypes and blood groups of the children . O+ could be : OO++ or OO+- therefore the blood group of the children: O+ or O- .

Example : The blood group of the mother is AO+- , and the blood group of the father is BO-- , Give the possible genotypes and blood groups of the children .

Blood Typing Test :

Using a standard technique , drops of blood are mixed with antisera that contain antibodies against the A and B and RH ( D ) antigens , and are then observed for the evidence of agglutination . If that particular antigen is present , agglutination occurs and the RBCs form visible clumps .
D

This blood is B+

Blood Typing Test
+
+
+
_
Anti A
Anti B
Anti D


Thank You