The Human Chromosome
Cytogenetics
•
•
•
•
Subdiscipline within genetics
Deals with chromosome variations.
Excess genetic material has milder effects
on health than a deficit.
Large-scale chromosomal abnormalities
present in all cells disrupt or halt prenatal
development.
DNA
Containing
genetic
information to
enable an
organism to
manufacture
all the proteins
required to
develop and
maintain an
organism
when
necessary.
Chromosome
The nucleus of
a cell contains
chromosomes
which carry
instructions for
the growth and
development
of an
organism. The
chromosomes
are made up
of long strands
of DNA.
Allele
The version of
genes called
alleles and
may be
different from
each other.
Chromosome
•
•
•
Primarily consists of DNA and protein.
Distinguished by size and shape.
Essential parts:
o Telomeres
o Origins of replication sites
o Centromere
Anatomy of Chromosome
•
•
•
•
•
•
•
Centromere – point where sister chromatids
are joined together.
Petit (P) – short arms; upward
Queue (Q) – long arm; downward
Telomere – tips of chromosome
Regions (p1, p2, p22 and q1, q22)
Bands (p1 1)
Sub-bands (p1 1.1)
Karyotype
Chromosome Chart
•
•
•
Confirm a clinical diagnosis.
Reveal effects of environmental toxins
Clarify evolutionary relationships.
Nomenclature Chromosome
•
•
•
International System for Human Cytogenetic
Nomenclature
Autosomes are numbered from 1-22, as
nearly as possible in descending order of
length.
Identification would be based on size, the
position of centromere and other
morphological features.
Example:
•
•
•
46, XY, dup (14) (q22q25) q
o Male with 46 chromosomes with a
duplication of chromosome 14 on
the long arm involving bands 22 to
25
46, XX, del (14) (q23)
o Female with 46 chromosomes with a
deletion of chromosome 14 on the
long arm at band 23.
46, XX, r (7) (q22q36)
o Female with 46 chromosomes with a
7 chromosome ring on the long arm
involving bands 22 to 36.
•
47, XY, +21
o Male with 47 chromosomes with an
extra at 21 chromosome.
Visualizing Chromosomes
•
•
Classes of Chromosomes
1. Telocentric - only one visible arm.
•
Tissue is obtained from person
Fetal tissue
o Amniocentesis
o Chorionic villi sampling
o Fetal cell sorting
o Chromosome microarray analysis
Adult tissue
o White blood cells
o Skin-like cells from cheek swab
Ultrasound image
2. Acrocentric - one short arm and one long
arm.
Amniocentesis
3. Submetacentric - similar arms but unequal
length.
•
•
•
Fetus at 15–16 weeks
Fetal cells suspended in the fluid around the
fetus are sampled.
Detects about 1000 of the more than 5000
known chromosomal and biochemical
problems.
Chorionic villus sampling
•
•
4. Metacentric - two arms in equal length.
•
•
•
Cells of the chorion are sampled.
Performed during 10–12th week of
pregnancy.
Provides earlier results than amniocentesis.
Does not detect metabolic problems.
Has greater risk of spontaneous abortion.
Staining Chromosomes
•
•
•
•
Chromosome Morphology
•
•
Best determined during metaphase.
Sister chromatids or Dyads are joined by
the centromere.
Dyes were used to stain chromosomes a
uniform color.
Were grouped into decreasing size classes,
designated A though G.
Improved staining techniques gave banding
patterns unique to each chromosome.
Researchers found that synchronizing the
cell cycle of cultured cells revealed even
more bands per chromosome.
Viewing Chromosomes
•
1882 and now
Indirect Detection of Extra Chromosomes
•
•
Maternal serum markers offer an indirect
method.
These are biochemicals whose levels are in
a normal range in a woman carrying a fetus
with a normal number of chromosomes but
lie outside the range with fetuses that have
an extra copy of a certain chromosome.
Maternal Serum Markers for Trisomy 21
FISH
•
•
•
Fluorescence in situ hybridization
DNA probes labeled with fluorescing dye
bind complementary DNA.
Fluorescent dots correspond to three copies
of chromosome 21.
Ideogram
•
•
Schematic chromosome map
Indicates chromosome arms (p or q) and
major regions delineated by banding
patterns.
Cell-Free DNA Testing
•
•
•
•
In the maternal blood are pieces of DNA
from the fetus.
Up to 20 percent of these pieces come from
the placenta, and thus represent the fetal
genome.
Testing DNA can detect certain fetal
chromosomal abnormalities, like some of
the trisomy conditions.
The test can be performed at 10 weeks into
the pregnancy.
Abnormalities in the Chromosome
Numerical Abnormalities
Atypical Chromosome Number
•
•
How Nondisjunction Leads to Sex Chromosome
Aneuploids
Euploidy is the state of an individual
possessing complete sets of chromosomes
with none extra or missing.
Numerical abnormalities involve gain or loss
of complete chromosomes.
o Polyploidy
o Aneuploidy
Trisomies
•
Autosomal aneuploids cease developing as
embryos or fetuses.
• Frequently seen trisomies in newborns are
those of chromosomes 21, 18, and 13.
o Carry fewer genes than other
autosomes.
1. Trisomy 21
• Down syndrome
• Most common trisomy among newborns
• Distinctive facial and physical problems
2. Trisomy 18
• Edwards syndrome
• Due to nondisjunction in meiosis II in oocyte
and generally do not survive.
• Serious mental and physical disabilities
• Distinctive feature— Oddly clenched fists
3. Trisomy 13
• Patau syndrome
• Very rare and generally do not survive 6
months.
• Serious mental and physical disabilities
• Distinctive feature— Eye fusion
Sex Chromosomes
1. Turner (XO) Syndrome
• One in 2500 female births
• 99% of affected fetuses die in utero.
• Features:
o Short stature
o Webbing at back of neck
o Incomplete sexual development
(infertile)
o Impaired hearing
• Individuals who are mosaics may have
children.
2. Triple-X Syndrome (XXX)
• One in 1000 female births
• Few modest effects on phenotype
include tallness, menstrual irregularities,
and slight impact on intelligence.
• X inactivation of two X chromosomes
occurs and cells have two Barr bodies
• May compensate for presence of extra
X.
3. Klinefelter (XXY) Syndrome
• One in 500 male births
• Phenotypes include:
o Incomplete sexual development
o Rudimentary testes and prostate
o Long limbs, large hands and feet
o Some breast tissue
development.
• Common cause of male infertility,
4. XXYY Syndrome
• Arises due to unusual oocyte and
sperm.
• Associated with more severe behavioral
problems than Klinefelter syndrome
• AAD, obsessive compulsive disorder,
learning disabilities.
• Individuals are infertile.
• Treated with testosterone.
2. Duplicated Sequence of genes
(Duplications)
5. Jacobs (XYY) Syndrome
• One in 1000 male births.
• 96% are phenotypically normal.
• Modest phenotypes
o Great height
o Acne
o Speech and reading disabilities.
• Studies suggest increase in aggressive
behaviors are not supported.
•
•
•
a) Charcot-Marie-Tooth
• Duplication
• Gene encoding peripheral myelin
protein 22 on chromosome 17
• Inverted champagne bottle
Chromosome Structural Abnormalities
1. Deleted Sequence of genes (Deletions)
3. Inverted Sequence of genes (Inversion)
Missing genetic segment from a
chromosome.
Often not inherited •
o Rather they arise de novo
Larger deletions increase the likelihood
that there will be an associated
phenotype.
•
a) Wolf-Hirschhorn syndrome
• Interstitial
• short arm of chromosome 4
b) Jacobsen syndrome
• Terminal
• End terminus of the long arm of
chromosome 11
c) Cri du Chat (cat cry) syndrome
• Terminal
• short arm of chromosome 5
•
•
•
•
Presence of an extra genetic segment on a
chromosome.
Often not inherited.
o Rather they arise de novo.
Effect on the phenotype is generally
dependent on their size.
o Larger duplications tend to have an
effect, while smaller ones do not.
•
Chromosome segment that is flipped in
orientation.
5–10% cause health problems probably due
to disruption of genes at the breakpoints
o Paracentric inversion—Inverted
region does not include centromere.
o Pericentric inversion—Inverted
region includes centromere.
May impact meiotic segregation.
4. Translocations
• Two nonhomologous chromosomes
exchange segments
• Types:
o Robertsonian translocation
▪ acrocentric chromosomes
fuse together.
▪ This fusing join two “long
arms” of DNA into one.
o Reciprocal translocation
▪ occur when part of one
chromosome is exchanged
with another.