Chromosomal aberrations are changes in chromosome structure that can be numerical or structural. Numerical abnormalities include aneuploidy, which is a change in chromosome number, and polyploidy, which is having more than two sets of chromosomes. Structural abnormalities include deletions, duplications, inversions, and translocations of chromosomal segments. Common aneuploidies in humans are trisomies such as Down syndrome (trisomy 21), Edward syndrome (trisomy 18), and Patau syndrome (trisomy 13). Sex chromosome aneuploidies include Klinefelter syndrome (XXY) and Turner syndrome (XO). Structural abnormalities can cause genetic disorders depending on
2. Cytogenetics
o Karyotype – microscopic examination of
chromosome
Main feature to identify and classify chromosomes
1. Size
2. Location of the centromere
3. Banding patterns
3. Chromosomal Aberration
o is substantial changes in
chromosome structure
o typically affect multiple
genes (loci)
o due to error in cell division
(non-disjunction of
chromosomes and
chromatids), maternal age
or environment
5. Types of Chromosomal Abnormalities
o aneuploidy
o polyploidy
Numerical
Abnormalities
Structural
Abnormalities
o deletion
o duplication
o inversion
o translocation
6. Numerical Abnormalities
o Aneuploidy
o Variation in the number of particular chromosomes within a set
1. Hyperploidy- gain of chromosome/s
• Trisomy- 2n + 1
• Double trisomy- 2n + 1 +1
• Tetrasomy- 2n + 2
2. Hypoploidy- loss of chromosome/s
• Monosomy- 2n –1
• Double monosomy- 2n –1-1
• Nullisomy- 2n-2
o Polyploidy
o Condition in which the cells have more than 2 homologous sets of chromosome
1. triploid (3n)
2. tetraploid (4n)
3. Pentaploid (5n)
7.
8. o Aneuploidy of sex
chromosome
o Occurs in 1 in 500-1000
o Sterile
o No obvious facial
dysmorphy
o Narrower shoulders and
wider hips
Klinefelter Syndrome – 47, XXY
9. o Smaller testes and penis
o Decreased sexual
interest
o Weaker bones
o Lower energy
o Breast growth
o Less facial and body hair
o Reduced muscle tone
Klinefelter Syndrome – 47, XXY
10. o Aneuploidy of sex
chromosome
o Aggressive due to high
level of testosterone
(prone to violent wife
beating)
o Adult male could be
more impulsive and
emotionally immature
Jacob Syndrome – 47, XYY
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11. o occurs in 1 in 1000
o lanky, clumsy,
uncoordinated
o dyslexia – develop in
reading disorder
o problem in motor
coordination
o behavioral problems
o behavioral tantrums
o more impulsive
oemotionally immature
Jacob Syndrome – 47, XYY
12. Turner Syndrome – 47, X
o Aneuploidy of the sex
chromosome
o demonstrate visuospatial
deficits including poor
handwriting and likely
underdeveloped
arithmetic skills
13. Turner Syndrome – Monosomy 47, X
o Short stature
o Ovarian failure
o otitis media
o early OM in TS could
lead in dyslexia (reading
disorder)
14. Patau’s Syndrome - Trisomy 13
o Severe intellectual
disability
o Physical abnormalities in
in many parts of the
body
o Heart defects, brain and
spinal cord abnormalities
15. Patau’s Syndrome - Trisomy 13
o Very small or poorly
developed eyes
(micropthalmia)
o Extra fingers or toes
o Weak muscle tone
(hypotonia)
16. Edward’s Syndrome – Trisomy 18
o intestines protruding
outside the body
o intellectual disabilities
o delayed development
o feeding and breathing
difficulties
17. Edward’s Syndrome – Trisomy 18
• o Arthrogryposis - a
•that joint
muscle
causes
disorder
multiple
contractures at birth
18. Down Syndrome - Trisomy 21
o physical growth delays
o severe degree of
intellectual disability
o short stature
o delayed mental and
social development
o Impulsive behavior
o Poor judgment
o Short attention span
o Slow learning
19. Down Syndrome - Trisomy 21
o Sleep apnea - sleep
disorder characterized
by pauses in breathing
or instances of shallow
or infrequent breathing
during sleep
o Dementia - decline in
mental ability severe
enough to interfere with
daily life, memory loss
o Hypothyroidism - under
active thyroid
20. Condition
Aneuploid Condition in Humans
Frequency Syndrome Characteristics
Trisomy 21 Mental retardation, abnormal pattern
of palm creases,slanted eyes,
flattened face, short stature
Trisomy 18 Mental and physical retardation,
facial abnormalities, extreme muscle
tone, early death
Trisomy 13 Mental and physical retardation, wide
variety of defects in organs, large
triangular nose, early death
XXY Sexual immaturity (no sperm), breast
swelling
XYY Tall
XXX Tall and thin, menstrual irregularity
X0
Autosomal
1/800 Down
1/6,000 Edward
1/15,000 Patau
Sex Chromosome
1/1,000 (males) Klinefelter
1/1,000 (males) Jacob
1/1,500 (females) Metafemale
1/1,500 (females) turner Short stature, webbed neck, sexualy
undeveloped
21. Effects of Nullisomics
• dwarf
• less tillering
• female fertile
• male sterile
• awnless
Nullisomics-Mutants of the Ear in
Wheat (Triticum aestivum)
Ear shape of the wild type (WT) and of
several mutants lacking single pairs of
chromosomes (nullisomics). Due to the
hexaploidy, the lack of a pair of
chromosomes is tolerated. The effects
are usually different though stunted
growth is usually one of them.
22. Polyploidy
- with more than 2 sets of genome
omost common in plants which are asexually propagated
and infrequent in animals
o for sexually reproducing organisms, sex chromosome
balance must be maintained
Detection:
• change in morphology
• change in fertility
• change in interspecific cross ability
24. Benefit of Odd Ploidy-Induced Sterility
Seedless fruit
watermelons and bananas
asexually propagated by human via cuttings
Seedless flowers
Marigold flowering plants
Prevention of cross pollination of transgenic
plants
26. Deletion
o Loss of a region of chromosome
o A chromosomal deficiency occurs when a chromosome breaks
and a fragment is lost
27. Phenotypic
consequences of
deficiency depends
on
Size of the deletion
Functions of the
genes deleted
Phenotypic effect of
deletions usually
detrimental
Deficiencies
Interstitial
Terminal
Two types of deletion
28. Cri-du-chat Syndrome
o High-pitched cry
o intellectual disability
o delayed development
o small head size
o low birth weight
o weak muscle tone in
infant
29. DiGeorge Syndrome
o deletion in long arm of
chromosome #22
o congenital heart disease
o Cyanosis
o learning difficulties
o psychiatric disorders
32. Duplication
o Small duplications often
are not accompanied by a
phenotypic effect
o Large duplications
produce phenotypes
through imbalanced gene
dosage
o tend to be less
detrimental
o constitute a major force of
genome evolution.
Direct Inverted
33. Inversion
o A segment of chromosome that is flipped relative to that in the
homologue
o Two breaks in one chromosome
o The fragment generated rotates 180o and reinserts into the
chromosome
Pericentric -
involves p and q
arm
Paracentric -
involves only
one arm
34. Inversion
o arise from chromosome entanglements and breakages during
meiotic prophase; also from recombination between
transposable elements
o Cause linear rearrangement of genes in a chromosome
o In inversion heterozygotes , a loop forms from the pairing of
the inverted and non-inverted regions
35. Translocation
o When a segment of one chromosome becomes
attached to another
o In reciprocal translocations two non-homologous
chromosomes exchange genetic material
o Usually generate so-called balanced translocations
o Usually without phenotypic consequences
o Although can result in position effect
37. Robertsonian Translocation
• Named after W. R. B. Robertson who
first identified them in grasshoppers in
1916
• Most common structural chromosome
abnormality in humans
– Frequency = 1/1000 livebirths
• Involves two acrocentric
chromosomes
• Two types
– Homologous acrocentrics involved
– Non-Homologous acrocentrics
involved
+ =
lost
+ =
lost
38. Robertsonian Translocation
This translocation occurs as such
Breaks occur at the extreme ends
of the short arms of two non-
homologous acrocentric
chromosomes
The small acentric fragments are
lost
The larger fragments fuse at their
centromeic regions to form a single
chromosome
This type of translocation is the most
common type of chromosomal
rearrangement in humans
39. Isochromosome & Ring Chromosome
o Mirror image chromosome
o Loss of one arm with
duplication of other
Loss of p-arm Duplication of q-arm
o Breaks occur in both arms of a
chromosome.
o The two broken ends anneal; the two
acentric fragments are lost.
o Results in double deletion (in p and in q).
o Epilepsy, mental retardation and
craniofacial abnormalities
