Transcript Typing Test

‫بسم هللا الرحمن الرحيم‬
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 .
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 Human
body
consist of trillions of
cells
 each cell nucleus
has 46 chromosomes
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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 .
Karyotype Test :
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
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 : picture of the chromosomes
in the nucleus of the cell used to check for
abnormalities .
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 :
•Amniotic fluid collected during an amniocentesis
•A piece
of the placenta
collected during a chorionic villi
sampling test ( CVS )
B - Postnatal Diagnosis :
Blood
sample
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Bone marrow
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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 :
A final karyotype analysis involves comparing
photographed chromosomes for following features:
the
1. Total chromosome number (e.g. Trisomies)
2. Sister chromatid length (e.g. deletions, translocations in
the p and q arms)
3. Placement of centromeres
4. Location and sizes of the chromosomal G-bands
(deletions, insertions, inversions)
The Result of Karyotype Test : Normal female karyotype 46,XX
•There are 46 chromosomes
Normal
that can be grouped as 22
Human
Karyotype: 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.
Abnormal:
•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.
Classification of Chromosomes according to
the Position of Centromere :
Human Chromosome Groups
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.
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Human Chromosomes
Cell nucleus
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Normal human male karyotype
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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:
Short, broad hands
Stubby fingers
Rough skin
Impotency in males
Mentally retarded
Small round face
Protruding tongue
Short lifespan
1 in 1,250 births
47 chromosomes
XY or XX
#21 Trisomy
Nondisjunction
Patau’s Trisomy Syndrome
1 in 14,000 births
47 chromosomes
XY 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
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 Monosomy
Nondisjunction
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 chromosomes
XXY only
#23 Trisomy
Nondisjunction
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 short
arm of chromosome 5
Abnormalities in Chromosome Structure
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
Chronic Myelogenous Leukemia
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 )
Philadelphia
Chromosome
The diagnostic Karyotype abnormality for
Chronic Myelogenous Leukemia shows
reciprocal translocation t ( 9 : 22 )
Philadelphia
chromosome
Burkitt Lymphoma
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 .
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 .
Abstract
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 .
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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 .
Activity
Phenotype
Frequency in
Population
IA IA, IA IO
α-3-N-acetyI-Dgalactosaminyltransferase
A
42%
IB IB, IB IO
α-3-Dgalactocyltransferase
Both enzymes
B
8%
AB
3%
None
O
47%
Genotype
IA IB
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
× IO IO → IA IO
IA I O
2- IA IO
× IO IO → IA IO
IO I O
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
Fathers'
Type
O
A
B
AB
O
O
O, A
O, B
A, B
A
O, A
O, A
O, A, B, AB
A, B, AB
B
O, B
O, A, B, AB
O, B
A, B, AB
AB
A, B
A, B, AB
A, B, AB
A, B, AB
Mother's Type
Rh Factor
Rh +
Rh -
Rh +
Rh +, Rh +
Rh +, Rh -
Rh -
Rh +, Rh -
Rh -
Father's Type
Inheritance of Blood Types
Inheritance of ABO and RH blood groups :
ABO & RH genes are not linked ,
ABO & RH (D ) type are inherited independently .
For example : An A RH ( D ) positive mother and a B RH ( D ) positive
father could have an O RH ( D ) negative child .
Inheritance of ABO and Rh(D)
Mother
Father
Group A AO
Group B BO
Rh(D) pos Dd
Rh(D) pos Dd
Group A AO
Group B BO
Group O OO
Rh(D) pos Dd
Rh(D) pos Dd
Rh(D) neg dd
ABO & Rh(D)
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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+O-
A+
A+
AO+-
AO+-
The blood group of the children : 100% A+
O-
A+
A-
AO+-
AO--
The blood group of the children : 50% A+ or AO-
A+
AO+-
O+
OO+-
The blood group of the children : 50% A+ or O+
O-
A+
A-
O+
O-
AO+-
AO--
OO+-
OO--
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 :
D
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 .
This blood is B+
Blood
Typing
Test
Anti A
Anti B
Anti D
+
+
+
_
Thank You