Clinical cytogenetics

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Clinical cytogenetics looks at the
morphology organization of human chromosomes
karyotyping important white blood
cells block mitosis in metaphase lyse the
cells fix stain or use a probe
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Clinical cytogenetics situations where
analysis is strongly recommended problems with
early growth development stillbirth neonatal
death fertility problems family
history neoplasia pregnancy in older women
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Female 46, XX
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Chromosome staining Q-banding quinacrine
stain G-banding giemsa stain
R-banding reverse banding C-banding
heterochromatin regions which remain
condensed regions near centromere are
heterochromatin FISH fluorescence in situ
hybridization probes for specific genes or
locations probes tagged with fluorescent
molecules Spectral karyotyping probes
specific for each chromosome, different colors
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chromosome identification bands numbered
from 1, starting near the centromere short arm
on the top, long arm on the bottom
centromere location key in identification metacen
tric in center arms about equal in
length submetacentric arms unequal acrocentric
centromere near one end telocentric
centromere at one end acrocentric
satellites on short arm
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chromosome identification G banding giemsa
stain unique staining pattern for each chromosome
p short arm, on top q long arm, on bottom
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special procedures C banding staining of
heterochromatin (condensed DNA) region near
centromere High-resolution banding
staining of less condensed chromosome regions
non-staining regions on several
chromosomes fragile sites (fragile X
mental retardation)
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special procedures FISH Fluorescence In
Situ Hybridization DNA probes for specific
chromosomes specific regions specific
genes detect chromosome rearrangements,
abnormal numbers
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Chromosome abnormalities euploidy or
polyploidy multiples of the N number of
chromosomes haploid 1N or 23
chromosomes diploid 2N or 46
chromosomes triploid 3N or 69
chromosomes tetraploid 4N or 92 chromosomes
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Chromosome abnormalities triploid 3N
due to dispermy found in 15-18 of
spontaneous abortions
enlarged headfusion of fingers
toesmalformations of mouth, eyes genitals
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Chromosome abnormalities tetraploid 4N or
92 chromosomes present in 5 of spontaneous
abortions
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Chromosome abnormalities changes in number
that are not a multiple of 23 addition or
deletion of individual chromosomes
aneuploidy 45 or 47 chromosomes monosomy 45
chromosomes trisomy 47 chromosomes
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aneuploidy monosomy one of a pair missing
(usually lethal) karyotype 45, XX -13 or
45, X trisomy three of one chromosome (XXY
trisomy 21) karyotype 47, XY 13 or 47, XX
13 non-disjunction is cause
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trisomy of autosomes trisomy 13 Patau
syndrome (47, 13) 1 in 15,000 live
births condition lethal phenotype facial
malformations eye defects extra fingers or
toes malformations of brain nervous
system congenital heart defects parental
age is a factor
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trisomy of autosomes trisomy 18 Edwards
syndrome (47, 18) 80 of live births are
female phenotype small at birth, grow
slowly mentally retarded clenched fists 2nd
5th fingers overlap 3rd 4th malformed feet
heart malformations common parental age is
a factor
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trisomy of autosomes trisomy 21 Down
syndrome (47, 21) most common trisomy
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trisomy of autosomes trisomy 21 Down
syndrome (47, 21) most common trisomy 1
in 900 live births leading cause of mental
retardation and heart defects phenotype
distinctive skin fold near eye epicanthic
fold spots in iris Brushfield spots
wide skull, flatter than normal at the back
tongue often furrowed and protruding
congenital heart defects in 40 of cases
physical growth, behavior and mental development
are retarded prone to respiratory
infections contract leukemia at higher rate
than normal parental age is a factor
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Sex chromosomes aneuploidy of sex
chromosomes Klinefelter syndrome 47,XXY
phenotype male Turner syndrome 45,X
phenotype female trisomy 47,XXX
significance reduced by X-inactivation 2 Barr
bodies only one X is active
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Klinefelter syndrome 47,XXY phenotype
male
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Klinefelter syndrome 47,XXY frequency 1
in 1,000 male births phenotype male other
features appear at maturity poor sexual
development low fertility breast
development in 50 of cases subnormal
intelligence in some many are mosaics - XY
and XXY cell lines in the
body non-disjunction occurred after
fertilization 60 due to maternal
non-disjunction maternal age is a factor
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Turner syndrome 45,X phenotype female
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Turner syndrome 45,X frequency 1 of all
conceptions 95-99 die before birth 1 in 10,000
female births phenotype female short
stature wide chest webbed neck underdeveloped
breasts narrowing of the aorta no mental
retardation but some mental
slowing ovaries underdeveloped
non-disjunction in 75 of cases associated with
the father
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Trisomy X 47,XXX