Transcript Genetics Lecture 15. Chromosome Aberrationsx

Cytogenetics
Study of Changes
in Chromosome Number
or Structure
Field Horsetail
1
Human Chromosomes
22 pairs of autosomes, one pair of sex chromosomes (X & Y)
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Genetic Testing
DNA analysis
Biochemical tests
Chromosome analysis
Chorionic villus sampling
Amniocentesis
3
Karyotype Analysis
Actively growing cells:
white blood cells, tissue biopsy
amniotic fluid, chorionic villi
Cultured in vitro:
mitotic cells arrested in metaphase
colcemid, colchicine
Fix cells on slide:
hypotonic swelling,
methanol/acetic acid, spread
Stain to visualize:
banding patterns, size, centromere
Capture image:
digital image
Prepare karyotype:
arrange chromosomes by size,
shape, cen, banding patterns
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Human Male Karyotype
G-banding
Ideogram
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Chromosome Descriptions
Centromere position:
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Chromosome Descriptions
Position of gene locus:
p arm
p13
q arm
q41
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Chromosome Abnormalities per 100,000 Pregnancies
Abort
Live
15% (10-25%)
of recognized
pregnancies
abort
spontaneously
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Changes in Chromosome Number
Ploidy - # of chromosome sets
Monoploid - basic set = n
Ex. humans, n = 23
haploid = 1n = 23
diploid = 2n = 46
Polyploid - multiple (>2 sets)
Triploid (3n),
Tetraploid (4 n),
Hexaploid (6)
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Changes in Chromosome Number
Endoreduplication can lead to instant evolution
Only a few animals tolerate polyploidy
Ex. salamanders, fish, frogs, lizards, chickens
Ex. salivary glands, myocardial cells
Polyploid humans
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Changes in Chromosome Number
Polyploidy - Common in plants
Karpechenko (1928) crossed radish with cabbage
X
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Changes in Chromosome Number
Polyploidy - larger commercial plants
Autopolyploidy
Allopolyploidy
amphidiploid or
allotetraploid
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Changes in Chromosome Number
Origin of
Amphidiploid
(Allotetraploid)
No homologous
chromosomes pair
No meiosis
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Aneuploidy - Gain or Loss of 1 or 2 Chromosomes
Results from Nondisjunction
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Aneuploidy - Gain or Loss of 1 or 2 Chromosomes
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Aneuploidy - Gain or Loss of 1 or 2 Chromosomes
Hypoploidy missing chromosomes
Autosomal monosomics undetected pregnancy
Hyperploid extra chromosomes
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Aneuploidy - Gain or Loss of 1 or 2 Chromosomes
Previously
covered
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Autosomal Trisomy
Trisomy 21 - Down syndrome, 2n + 1 = 47, 1 in 700 live births
Mental retardation, skin folds (epicanthic) corner of eyes,
Skull wide, flattened at back, iris spots, protruding tongue
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Autosomal Trisomy
Trisomy 18 - Edwards syndrome, 2n + 1 = 47, 2.5 in 10,000 live births
Small, slow growth, low set malformed ears, malformed feet,
mental retardation. Most die of heart problems within 6 months.
Characteristic fist clenching, rocker feet
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Autosomal Trisomy
Trisomy 13 - Patau syndrome, 2n + 1 = 47, 1 in 15,000 live births
Cleft lip and palate common, small eyes, polydactyly,
heart, brain, nerve defects, mental & developmental retardation
Most die within 3 months
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Somatic Aneuploids
Result from nondisjunction during development (mitosis)
Mosaics
Ex.
XY/XXY Partial Klinefelter syndrome
XO/XYY Gynandromorph, split sex
XX
w w+
m m+
XO
XXX
w
m
w w+ w+
m m + m+
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Chimeras
Two embryos fuse - one individual with two genotypes
Chances increase with in vitro fertilization
Female/Male - hermaphrodite
Sperm, blood, hair - distinct DNA profiles
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Changes in Chromosome Structure
Summary of Chromosome Rearrangements
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Deletion - del - 
Many genes
may be lost
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Deletion - del - 
Cri-du-chat syndrome - deletion 5p
severe mental retardation, numerous physical abnormalities
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Duplication
Arise through replication slippage or unequal crossing over
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Duplication
Arrangements of duplicate genes
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Duplication
Duplicate genes - can be important in evolution
Multigene families
Ex. hemoglobin genes clustered
Different ones expressed
in embryo, fetus, and adult
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Duplication
Region 16A duplication - Bar eyes in Drosophila
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Duplications
Trinucleotide repeat expansion – (CCGn)
Ex. Fragile X - mental retardation
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Inversions
Breakage and rejoining of chromosome segments
Paracentric
Pericentric
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Consequences of Paracentric Inversions
Loop forms to
Align genes
Crossover within
inversion loop
leads to
Acentric and
Dicentric
fragments
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Consequences of Paracentric Inversions
Breakage
occurs during
Anaphase
Results in
gene loss
Lethal
CO suppression
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Consequences of Pericentric Inversions
CO in inversion
loop results
in
Deletions
Duplications
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Translocations
Exchange between nonhomologous chromosomal regions
Nonreciprocal
Reciprocal
Balanced – correct number of genes, rearranged
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Consequences of Translocations
Reciprocal
Translocation
Heterozygote
Duplications
Deletions
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Consequences of Translocations
Familial Down
Syndrome
Translocation
Carrier
One possible
outcome
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Consequences of Translocations
Familial Down
Syndrome
Translocation
Carrier
Second
possible
outcome
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Consequences of Translocations
Familial Down
Syndrome
Translocation
Carrier
Third
possible
outcome
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Consequences of Translocations
Cri-du-chat syndrome – due to translocation in parent
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Consequences of Translocations
Chronic myelogenous leukemia – uncontrolled replication myeloblasts
Philadelphia chromosome – translocation 22 & 9
ABL protooncogene
from 9
fuses with
BCR on 22.
Fusion protein
stimulates
cell growth.
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Robertsonian Translocations
Fusion of chromosomes at centromeres – important in evolution
Rodents
telocentrics
Chimpanzee
Human
none
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Detection of Translocations
FISH - chromosome painting – reciprocal exchange
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