Download Leture 19, work session 12

Chromosome , Karyotype and Numerical
Chromosomal Abnormalities
Dr.Aida Fadhel Biawi
Chromosome - what is, definition and function
Chromosome is a coiled DNA molecule within the cell’s nucleus that carries an
individual’s GENETIC CODE .Most of the time the chromosome’s structure is loose
and indistinguishable. Only in the stage of cell division immediately before the cell
divides (the metaphase) does the chromosome draw itself into a compact, rodlike
structure the geneticist can see under a microscope after applying a special dye to the
cell that the chromosomes absorb. It is this ability to absorb a colored dye that gives
the chromosome its name, which means “colored body”.
Centromere - the position on a CHROMOSOME where the
chromosome separates during cell division .The centromere is a
structure of noncoding DNA( DNA that does not convey genetic
information). When the cell divides the strands of the chromatids
migrate in opposite directions (pull apart) at the centromere. In a
photomicrograph, the centromere appears as an indented, waistlike
area on the chromosome. Geneticists use the centromere’s position,
along with other characteristics of the chromosome, to match
chromosomes into their pairs when creating KARYOTYPES.
Telomere - definition
Telomere is a structure of noncoding DNA( DNA that does not convey
genetic instruction) at each end of a CHROMOSOME .Telomeres are
essential for chromosome duplication during cell division. They function as
handles to pull the chromatids (dividing chromosomes) apart as the mother
cell divides into the two new daughter cells.
Chromosome Complements
The nucleus of every diploid cell, also called a SOMATIC CELL ,contains the
full complement of 46 chromosomes arranged in 23 pairs. One pair contains
the sex chromosomes that establish gender, paired either as XX (female) or
XY (male). The other 22 pairs are autosomes. The haploid cells, the gametes
(spermatozoa and OVA), contain one half the chromosome complement.
When gametes merge in CONCEPTION the diploid cell they form, the
ZYGOTE, acquires the full chromosomal complement. The only cells in the
body that do not have chromosomes are the erythrocytes, which do not have
nuclei .
Autosomes carry the bulk of genetic code. Thousands of genes
line each autosome, each in its ordained position. The sex
chromosomes carry several hundred genes. The GENE positions,
called loci (in the singular, each position is a locus), are constant.
For example, the gene loci for the ABO BLOOD TYPE are always
on chromosome 9, those for the rhesus (Rh) blood type are on
chromosome 1, and those for EYE color on chromosomes 15 and
19 .
Chromosome Size
The HUMAN GENOME PROJECT, completed in 2003, revealed the
structure of chromosomes to be much larger and more complex than
scientists previously had theorized. Chromosome 1, the largest
CHROMOSOME, contains 2,968 genes. The smallest chromosome, the Y
chromosome, contains 231 genes.
autosome - definition
Autosome is a CHROMOSOME that appears as a pair in
which both chromosomes are the same in either sex, also
called a nonsex chromosome .In contrast, the sex
chromosomes appear as a pair that is different in males and
females. The human GENOME contains 22 autosomes and one
pair of sex chromosomes for a total complement of 46
chromosomes as 23 pairs.
Sex Chromosome - definition
Sex Chromosome - the structure of GENETIC CODE that
determines gender (male or female .)The male sex CHROMOSOME
has the appearance of the letter Y and the female sex chromosome has
the appearance of the letter X. A combination of XY results in male and a
combination of XX results in female. The Y chromosome contains fewer
than 100 genes, while the X chromosome carries several hundred
genes. A number of GENETIC DISORDERS are X-linked that is, they
result from mutations that occur among genes the X chromosome
carries. HEMOPHILIA and some forms of MUSCULAR DYSTROPHY
(notably Duchenne’s and Becker’s) are X-linked genetic disorders.
Nomenclature of chromosomes
Chromosomes in eukaryotes and
prokaryotes are different
PROKARYOTES
EUKARYOTES
single chromosome plus plasmids
many chromosomes
circular chromosome
linear chromosomes
made only of DNA
made of chromatin, a nucleoprotein
(DNA coiled around histone
proteins)
found in cytoplasm
found in a nucleus
copies its chromosome and divides
immediately afterwards
copies chromosomes, then the cell
grows, then goes through mitosis to
organise chromosomes in two equal
groups
Organism
Human
Chromosome
numbers
46
Chimpanzee
48
House Mouse
40
Maize
20
Karyotype - definition
Karyotype is a pictorial presentation of an
individual’s chromosomes, taken from
microphotographs (photographs taken through a
microscope) and arranged in a numeric sequence that
aligns the chromosomes from largest to smallest .This
standardized presentation allows the geneticist to analyze
an individual’s chromosomal profile. A geneticist can
structure a karyotype from any SOMATIC CELL( non-sex
cell) in the body. The most common application of
karyotyping is GENETIC SCREENING of a fetus. A
geneticist constructs a karyotype to evaluate whether an
individual has a GENETIC DISORDER. A karyotype
requires DNA from a representative cell in the body, from
which the geneticist extracts and prepares the DNA for
examination under the microscope.
Somatic cells used to get
Karyotype :
1- Peripheral blood
2- Amniotic fluid
3- Chronic Villi
4- Tumor Cells
5- Bone marrow cells
Amniocentesis
Chorionic villus sampling
How to get Karyotype ??
Final Step in Karyotype (Manual(
Human karyotype
Karyotype (by software)
Metaphase chromosomes
Karyotyped chromosomes
G-Banding
Dye gives chromosomes a striped appearance
because it stains the regions of DNA that are rich in
adenine (A) and thymine (T) base pairs.
G-Banding
• Regions that stain as dark G bands
replicate late in S phase of the cell cycle
and contain more condensed chromatin,
• While light G bands generally replicate
early in S phase, and have less
condensed chromatin.
Chromosome Groups
Group
Chromosomes
Description
A
1–3
Largest; 1 and 3 are metacentric but 2 is submetacentric
B
4,5
Large; submetacentric with two arms very different in size
C
6–12,X
Medium size; submetacentric
D
13–15
Medium size; acrocentric with satellites
E
16–18
Small; 16 is metacentric but 17 and 18 are submetacentric
F
19,20
Small; metacentric
G
21,22,Y
Small; acrocentric, with satellites on 21 and 22 but not on
the Y
Autosomes are numbered from largest to smallest, except that chromosome 21 is
smaller than chromosome 22.
Fluorescence in situ Hybridization
Fluorescence in situ
Hybridization (FISH)
• FISH - a process which clearly
paints chromosomes or portions
of chromosomes with
fluorescent molecules
Fluorescence in situ
Hybridization (FISH)
• Identifies chromosomal
abnormalities
• Aids in gene mapping,
• analysis of chromosome
structural aberrations, and ploidy
determination
Detection single gene by FISH Technique
Detection whole chromosome by FISH Technique
FISH - fluorescence in situ hybridisation
Detection centromeric region by FISH Technique
Detection telomeric by FISH Technique
Numerical chromosomal abnormalities :
1- Aneuploidies)-- the presence of an extra chromosome (trisomy) or a
missing chromosome (monosomy) -- result from segregation errors
during cell division: Chromosomes do not divide evenly among daughter
cells (nondisjunction) (see Fig. 2).
For unknown reasons, trisomies are positively associated with
advanced maternal age. .
2- Polyploidy refers to the presence of an extra set of chromosomes.
Triploidy, for example, usually occurs when 2 spermatozoa fertilize an
oocyte, resulting in a zygote that contains 3 sets of chromosomes
instead of 2 . Numerical abnormalities are sporadic, and they do not
usually recur in subsequent pregnancies .
3- Mosaicism
4- Chimerism
Aneuploidy as a consequence of non-disjunction
Polyploidy
Mosaicism denotes the presence of two or more populations of cells
with different genotypes OR DIFFERENT CELL LINES in one individual
who has developed from a single fertilized egg .
A chimera or chimaera is a single organism( usually an animal )that is
composed of two or more different populations of genetically distinct cells that
originated from different zygotes involved in sexual reproduction.
A chimeric mouse with its offspring
Aneuploidy in Autosomes
1- Down Syndrome (Trisomy 21)
2- Patau Syndrome (Trisomy13)
3- Edward Syndrome (Trisomy 18)
Down’s Syndrome
Patau’s Syndrome
Edward’s Syndrome
Aneuploidy in Sex Chromosome
1- Klinefilter Syndrome (47, XXY)
2- Turner Syndrome (46,x0 )
3- XYY male (Jacob’s Syndrome)
4- Triple X female (xxx ) female.
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
Ethical Issues in Genetics and Molecular Medicine
Ethical Issues in Genetics and Molecular Medicine - the questions and
concerns that arise for physicians and individuals in regard to the
information GENETIC SCREENING ,GENETIC TESTING ,and genetic and
molecular therapies .Though advances in genetics have produced significant
breakthroughs in understanding, diagnosing, and sometimes treating health
conditions that occur as a result of GENETIC DISORDERS ,doctors and their
patients grapple with the ethics of both research and therapeutics.
The issues touch many of what have long been the sacred tenets of the practice
of medicine: privacy, access to care, autonomy in decision making, and protection
against discrimination .
Thank You