Cytogenetics Human Chromosome Centromeres
Largest constriction of the chromosome and
where spindle fibers attach
INTRODUCTION
Bases that form the centromere are repeats of a
Genetic variation refers to differences between 171-base DNA sequence
members of the same species or those of different Replicated at the end of S-phase
species Facilitated by centromere protein A
CENP-A is passed to next generation
Allelic variations are due to mutations in
Example of an epigenetic change
particular genes
Chromosomes may differ in the Position of the
Chromosomal aberrations are substantial
Centromere.
changes in chromosome structure
These typically affect more than one
gene
They are also called chromosomal
mutations
VARIATION IN CHROMOSOME STRUCTURE
The study of chromosomal variation is important for
several reasons
1. They can have major effects on the phenotype
of an organism
2. They can have major effects on the phenotype
Telomere
of the offspring of an organism
3. They have been an important force in the chromosome tips composed of many repeats of
evolution of specie TTAGGG
Shorten with each cell division
CHROMOSOMES
provide terminal stability to the chromosome
Rod-shaped, filamentous bodies present in the and ensure its survival
nucleus
They are the carriers of the gene or unit of
Subtelomeres
heredity.
They are not visible in active nucleus due to Chromosome region between the centromere
their high water content, but are clearly seen and telomeres
during cell division. Consists of 8,000 to 300,000 bases
Two essential features of all eukaryotic Near telomere the repeats are similar to the
chromosomes telomere sequence
Centromeres Contains at least 500 protein-encoding genes
Telomeres About 50% are multigene families that
Each provide a unique function which is include pseudogene
absolutely necessary for the stability of the
chromosome
CHROMOSOMAL BAND
CHROMOSOME SIZE Autosomes VS Sex Chromosome
Size of chromosomes shows a remarkable
variation depending upon the stages of cell
division.
Interphase: chromosome are longest &
thinnest
Prophase: there is a progressive decrease in
their length accompanied with an increase
in thickness
Anaphase: chromosomes are smallest.
Metaphase: Chromosomes are the most
easily observed and studied during
metaphase when they are very thick, quite
short and well spread in the cell
CHROMOSOME NUMBER
Presence of a whole sets of chromosomes is called
Euploidy
Gametes normally contain only one set of
chromosomes –this number is called
Haploid
Somatic cells usually contain two sets of
chromosome -2n : Diploid
The condition in which the chromosomes sets are
present in a multiple of “n” is Polyploidy
3n –triploid
4n –tetraploid
CHROMOSOME DETECETION
Direct Visualization of Indirect Visualization of
Chromosomes Chromosomes
•Karyotyping •Beta human chorionic
•Amniocentesis gonadotropin
•Chorionic Villi Sampling •Inhibin A
•FISH •Estradiol
•Alpha fetoprotein
•Pregnancy-associated
plasma protein
When a change in the chromosome number does Cytogeneticists use three main features to identify
not involve entire sets of chromosomes, but only a and classify chromosomes
few of the chromosomes -is Aneuploidy. Size
Monosomics (2n-1) Location of the centromere
Trisomics (2n+1) Banding patterns
Nullisomics (2n-2) These features are all seen in KARYOTYPE
Tetrasomics (2n+2)
KARYOTYPE
Pictorial or photographic representation of all the
different chromosomes in a cell of an individual,
chromosomes are usually ordered by size and
numbered from largest to smallest.
For detailed identification, chromosomes are
Karyotype Idiotype treated with stains to produce characteristic
banding patterns
General morphology of the Diagram version of
Example: G-banding
somatic chromosome. karyotype showing all the
Generally, karyotypes morphological features of Chromosomes are exposed to the dye
represent by arranging in the chromosome. Giemsa
the descending order of Some regions bind the dye heavily
size keeping their Dark bands
centromeres in a straight Some regions do not bind the stain well
line. Light bands
In humans
300 G bands are seen in metaphase
2,000 G bands in prophase
Useful at several levels
Confirm a clinical diagnosis
Reveal effects of environmental toxins
Clarify evolutionary relationships
Direct Visualization Specimen Collect
Fetal Tissue Adult Tissue
▪Amniocentesis ▪White blood cells Detecting Chromosomes
▪Chorionic villi sampling ▪Skin-like cells from cheek
▪Fetal cell sorting swab The banding pattern is useful in several ways:
▪Chromosome microarray 1. It distinguishes Individual chromosomes from
analysis each other
2. It detects changes in chromosome structure
3. It reveals evolutionary relationships among the
chromosomes of closely related species
Cytogenetics Notation
Abbreviation Definition
46, XY Normal Male
46, XX Normal Female
45, X Turner syndrome (Female)
47, XXY Klinefelter syndrome (male)
47, XYY Jacob’s syndrome (male)
46, XY,del(7q) A male missing part of the
long arm of chromosome 7
47, XX, +21 Female with trisomy 21
46, XY, Male with a translocation
t(7;9)(p21.1;q34.1) between the short arm of Polyploidy
chromosome 7 at band 21.1
Cell with extra chromosome sets
and long arm of chromosome
9 at band 34.1) Triploid (3N) cells have three sets of chromosomes
Produced by:
Fertilization of one egg by two sperm
Direct Visualization of Chromosome Fusion of haploid and diploid gametes
Fluorescence in situ hybridization Account for 17% of all spontaneous
abortions and 3% of stillbirths and
DNA probes labeled with fluorescing dye bind newborn death
complementary DNA
Fluorescent dots correspond to three copies of
chromosome 21
Amniocentesis
Removal of small sample of amniotic fluid from the
uterus using a needle passed through the mother
abdominal wall
Ultrasound is used to follow needle’s movement
Detects about 1,000 of the more than 5,000 known
chromosomal and biochemical problem
Chorionic Villus Sampling Aneuploidy
Obtaining cells from the chorionic villi –finger-like Normal chromosomal number is euploid
structures that develop into the placenta Cells with extra or missing chromosomes are
Performed during 10-12th week of pregnancy aneuploid
Provides earlier results than amniocentesis Autosomal aneuploids are spontaneously aborted
Does not detect metabolic problems Those born are more likely to have an extra
Has greater risk of spontaneous abortion chromosome (trisomy) rather than a missing
one (monosomy)
Nondisjunction
Meiotic error that causes aneuploidy
Produces gamete with an extra chromosome and
another with one missing chromosome
Nondisjunction during Meiosis I result in copies of
both homologs in one gamete
Nondisjunction during Meiosis II results in both sister
chromatids in one gamete
Chromosomes Abnormalities
Karyotype may be abnormal in
Chromosome number
Chromosome structure
Abnormal chromosomes account for at least 50% of
spontaneous abortions
People are being diagnosed with chromosomal
abnormalities due to improved technology
Aneuploidy Duplications
Arises during mitosis, producing groups of somatic Presence of an extra genetic segment on a
cells with the extra or missing chromosomes chromosome
Individual with two chromosomally distinct cell Often not inherited
populations is called a mosaic Rather they arise de novo
Mitotic nondisjunction event that occurs early in Effect on the phenotype is generally dependent on
development can have serious effects on the health their size
of the individual Larger duplications tend to have an effect, while
smaller ones do not
Trisomy
Autosomal aneuploids cease developing as embryos
or fetuses
Frequently seen trisomiesin newborns are those of
chromosomes 21, 18, and 13
Carry fewer genes than other autosomes
Translocation
Two non-homologous chromosomes exchange
segments
Types
Robertsonian translocation
Reciprocal translocation
Robertsonian
Two non-homologous acrocentric chromosomes
break at the centromere and their long arms fuse
Short arms are often lost
Affect 1 in 1,000 people
Translocation carriers have 45 chromosomes
Produce unbalanced gamete
Tends to recur in families, who also have more risk
of spontaneous abortions
One of the parents is a translocation carrier
May have no symptoms
Distribution of the unusual chromosome
leads to various imbalance
Deletion
Missing genetic segment from a chromosome
Reciprocal
Often not inherited
Rather they arise de novo
Two nonhomologous chromosomes exchange
Larger deletions increase the likelihood that there parts
will be an associated phenotype One in 500 people are carriers
Cri-du-chat (cat cry) syndrome Usually healthy because they have the
Deletion 5p– normal amount of genetic material
Translocation breakpoint interrupts a gene, there
may be an associated phenotype
Inversion
Chromosome segment that is flipped in orientation
5-10% cause health problems probably due to
disruption of genes at the breakpoints
Paracentric inversion -Inverted region does not
include centromere
Pericentric inversion -Inverted region includes
centromere
May impact meiotic segregation
Isochromosomes
Chromosomes with identical arms
Formed when centromeres divide along the
incorrect plane during meiosis
Occur in 1 of 25,000 conceptions
Arise when telomeres are lost and sticky
chromosome ends fuse
Genes can be lost or disrupted causing symptom
