Ch.
15: Chromosomal Abnormalities
Abnormalities in Chromosomal
Number
Abnormalities in Chromosomal
Structure:
Rearrangements
Fragile Sites
.
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Prophase
.
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Prophase
.
Pro metaphase
.
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Metaphase
.
Anaphase
.
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Telophase
.
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Cytokinesis
.
The chromosomes can be:
counted
banded by staining
grouped according to size, banding pattern, etc.
probed for specific DNA sequences
.
Counting reveals disorders associated with
abnormal numbers of chromosomes (e.g.
trisomy one, for example, Down's
syndrome).
Banding is a technique revealing, at a
gross level, the structure of a chromosome.
This reveals alternating light and dark
bands characteristic to each chromosome;
the light bands comprise euchromatin
(gene-rich DNA); the dark bands comprise
heterochromatin (rich in repetitive sequenc
.
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• Define:
– nondisjunction
– polyploidy
– aneupoidy
– trisomy
– monosomy
.
Abnormalities in chromosomal number
How does it happen?
.
Chromosomal variation can be :-
1-structural changes (affect basic
structure).
2- numerical changes(chromosome set).
.
1-structural variation
It is genes loci exchanging in chromosomes,
du to translocation of chromosomal group.
The factor that mentined chromosome
breaking are :-
1- radiation(x ray).
2- chemicals(mustard gas).
3- heat shock( high or low- c◦).
4- normally under unknown conditions.
.
structural variation types
1- deletion (missing of chromosome part=
gene or more)can be:-
Terminal deletion( lacking of centromere).
Intercalary deletion(two breaking &
jointing).
Deletion is useful in genes loci determination
(lead to recessive characters in hygiene =
pesudo-dominance).
.
2- duplication (addition of copies du to
unequal crossing over)
Useful in quantitative genetic.
3- inversion (paracentric or pericentric ).
Useful in position effect.
4- translocation (simple or reciprocal
(exchanged))
.
Variations in number
1- Aneuploidy (adition or deletion in one
or group of chromosome) can be :-
Trisomic (2n+1)chromosome.
Monosomic(2n-1)chromosome (nonviable).
Tetrasomic (2n+2)chromosome.
Nullsomic (2n-2) chromosome. (
CYTOGENETIC=DOWS syndrome )
.
2- polyploidy (lead to duplication of bacic
chromosome numbers)can be :-
a-Autoployploidy :-
1- monoploid (n).
2- diploid(2n).
3- Triploid (3n).
4- Tetraploid (4n).
b- Allopolyploidy Allotetraploid)
in human lead to un fertilized form. .
Abnormalities in chromosomal number
Non disjunction - mistake in cell
division where chromosomes do not
separate properly in anaphase
usually in meiosis, although in
mitosis occasionally
in meiosis, can occur in anaphase I
or II
.
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.
Abnormalities in chromosomal number
polyploidy – complete extra sets (3n, etc.) –
fatal in humans, most animals
aneuploidy – missing one copy or have an
extra copy of a single chromosome
three copies of a chromosome in your somatic cells:
trisomy
one copy of a chromosome in your somatic cells:
monosomy
most trisomies and monosomies are lethal well
before birth in humans; exceptions will be covered
.
Abnormalities in chromosomal number
generally, in humans autosomal aneuploids tend
to be spontaneously aborted
over 1/5 of human pregnancies are lost
spontaneously after implantation (probably closer to
1/3)
chromosomal abnormalities are the leading known
cause of pregnancy loss
data indicate that minimum 10-15% of conceptions
have a chromosomal abnormality
at least 95% of these conceptions spontaneously
abort (often without being noticed) .
• Define:
– nondisjunction
– polyploidy
– aneupoidy
– trisomy
– monosomy
.
• Describe each of the aneuploidies that
can be found in an appreciable number
of human adults (chromosomal
abnormality, common name of the
syndrome if it has one, phenotypes)
.
aneuploidy in human sex chromosomes
X_ female (Turner syndrome)
short stature; sterile (immature sex organs); often reduced
mental abilities
about 1 in 2500 human female births
XXY male (Klinefelter syndrome)
often not detected until puberty, when female body
characteristics develop
sterile; sometimes reduced mental abilities; testosterone shots
can be used as a partial treatment;
about 1 in 500 human male births
.
aneuploidy in human sex chromosomes
XYY male (XYY syndrome)
usually tall, with heavy acne; some correlation with mild
mental retardation and with aggressiveness; usually still fertile
about 1 in 1000 human male births
XXX female (triple X syndrome)
usually just like XX females, except for having 2 Barr bodies in
somatic cells
HOWEVER, more likely to be sterile, and if fertile, more likely
to have XXY and XXX children
about 1 in 1000 human female births
.
aneuploidy in human autosomes
autosomic monosomy appears to be invariably fatal,
usually very early in pregnancy
most autosomic trisomy is fatal, but sometimes
individuals trisomic for autosomes 13, 15, 18, 21, or
22 survive to birth and even beyond
chromosome number reflects size; bigger number = smaller
size, and usually fewer genes
extra 13, 15, or 18 leads to multiple defects and usually death
well before 1 year of age
extra 22 is much like extra 21 (Down syndrome, covered
next), but usually more severe, with shorter life expectancy
.
aneuploidy in human autosomes
trisomy 21 (Down syndrome)
only human autosomal trisomy that
generally allows survival to
adulthood
found in about 1 in 750 live births
a phenotypically identical condition
involves a chromosomal
translocation (covered later)
traits include:
abnormal facial appearance
high likelihood of mental retardation
(degree varies considerably)
increased likelihood of developing
leukemia and Alzheimer’s disease
.
Maternal Age Effect for Down Syndrome
likelihood of a child being born with
Down syndrome increases with the
age of the mother
rate is as high as 1 in 16 live births
for mothers age 45 and over at
conception
not completely clear why the odds
go up so dramatically, likely a
combination of factors
is clear that nondisjunction is more
common in eggs than sperm
appears that spontaneous
rejection of aneuploid pregnancies
is more common in younger
women
.
• Describe each of the aneuploidies that
can be found in an appreciable number
of human adults (chromosomal
abnormality, common name of the
syndrome if it has one, phenotypes)
.
• Draw an inversion, a deletion, a
duplication, and a reciprocal
translocation.
.
Ch. 15: Chromosomal Abnormalities
Abnormalities in Chromosomal
Number
Abnormalities in Chromosomal
Structure:
Rearrangements
Fragile Sites
.
Abnormalities in chromosomal structure:
chromosomal rearrangements and fragile sites
in addition to nondisjunction errors, there
can be errors in homologous chromosome
pairing and in crossing over; these produce
chromosomal rearrangements:
reciprocal translocations
inversions
deletions
duplications
.
Abnormalities in chromosomal structure:
chromosomal rearrangements and fragile sites
reciprocal translocation – nonhomologous
chromosomes pair and exchange parts (if only
one gets new material, this is just called a
translocation)
can lead to deletions (loss of genetic material) and
duplications (extra copies of genetic material)
.
Abnormalities in human chromosomal structure:
chromosomal rearrangements and fragile sites
somewhat common in humans is a
translocation of chromosome 21 to
chromosome 14
this is called translocation Down syndrome,
accounting for about 3% of all phenotypic Down
syndrome individuals
results in only 45 chromosomes in body cells of
carrier (has one chr 14, one chr 21, one 14/21 =
normal phenotype), but that individual has a high
chance of producing offspring that are essentially
trisomy 21 (with one chr 14, two chr 21, and one
14/21)
.
Abnormalities in human chromosomal structure:
chromosomal rearrangements and fragile sites
inversion – part of a chromosome is “flipped”
relative to the normal gene sequence; can also
lead to deletions and duplications
.
Abnormalities in human chromosomal structure:
chromosomal rearrangements and fragile sites
deletion
causes include losses from translocations,
crossovers within an inversion, and unequal
crossing over
can also be caused by breaking without rejoining,
usually leading to large deletions
small deletions are less likely to be fatal; large
deletions are usually fatal – but always, there is
variation based on what genes are lost
.
Abnormalities in human chromosomal structure:
chromosomal rearrangements and fragile sites
deletion
some medium-sized deletions lead to recognizable
human disorders
several syndromes have been described that
correspond to deletions of certain chromosomal
regions; most commonly found in live births in
humans is deletion of the short arm of chr 5
called cri du chat (cat’s cry) syndrome
found in about 1 in 50,000 live births
surviving infants have a distinctive cry, severe mental
retardation, and shortened lifespan
.
Abnormalities in human chromosomal structure:
chromosomal rearrangements and fragile sites
duplication
causes include extras from translocations,
crossovers within an inversion, and unequal
crossing over
again, amount makes a difference, with larger
duplications more likely to be fatal, but there is
variation based on what genes are duplicated
duplications also provide raw material for genetic
evolution; for example, there are many
pseudogenes in humans that are “inactivated”
duplicates
.
• Draw an inversion, a deletion, a
duplication, and a reciprocal
translocation.
.
• Describe trinucleotide repeat disorders.
.
Abnormalities in human chromosomal structure:
chromosomal rearrangements and fragile sites
fragile sites
some chromosomes have regions that are
poorly connected to the rest of the
chromosome;
the “poor connection” is often a string rich in
CGG or CGC repeats, and is inherited like a
gene
breaks from these fragile sites lead to loss of
genetic material
.
Abnormalities in human chromosomal structure:
chromosomal rearrangements and fragile sites
fragile X syndrome
effects center on
decreased mental capacity
more prominent effects in
males than females
like other trinucleotide
repeat disorders, repeat
number may increase from
one generation to the next
other fragile sites may
play a role in cancer
.
• Describe trinucleotide repeat disorders.