-
Cytogenetics looks for changes in what?
the karyotype
-
Chromosome Layout
- • Karyotype/Karyogram: formally laid out chromosomes
- • chromosomes are matched & laid out in pairs from 1- 22
- • p (short arm) goes up & q (long arm) goes down
- • centromere divides chromosome into p & q
-
Chromosome Centricity
• Metacentric: the centromere is in the middle so p & q are approximately the same length
• Submetacentric: the centromere divides the chromosome into 2 arms of strikingly different length
• Acrocentric: have satellite region where centromere would be
-
Telomere
loop structure found at the end of chromosomes that prevent them from unwinding
-
What do chromosomes in metaphase look like?
they consist of 2 chromatids
-
What are constitutional Prenatal indicators a karyotype analysis should be conducted?
- • advanced maternal age
- • ultrasound abnormalities
- • abnormal screening test
-
What are constitutional Perinatal (period around childbirth) indicators a karyotype analysis should be conducted?
- • confirmation of a clinical diagnosis
- • ambiguous genitalia
- • multiple congenital dysmorphic features
-
What are constitutional indicators in Childhood a karyotype analysis should be conducted?
- • short stature
- • developmental delay
-
What are constitutional indicators in Adulthood a karyotype analysis should be conducted?
• history of pregnancy loss
-
What is the only Acquired indicator for a karyotype analysis?
hematological malignancy: cancer that affects blood, bone marrow & lymph nodes
• can be an indicator for a child or an adult
-
What is the difference between a numerical constitutional change and a structural constitutional change?
• numerical constitutional change: gain or loss of a chromosome
• structural constitutional change: translocation, deletion, duplication, inversion or insertion of chromosomal material
-
What numerical constitutional chromosomal changes (chromosome losses/gains) are compatible with life?
- 1. Trisomy 13, 18, 21
- 2. Trisomy X, Y
- 3. Loss of an X or Y chromosome
- • ALL OTHER TRISOMIES are associated with infertility or pregnancy loss
-
Most Frequent Liveborn Trisomies (6):
- • 13 (Patau Syndrome)
- • 18 (Edwards Syndrome)
- • 21 (Down Syndrome)
- • Turner Syndrome (1 X)
- • Klinefelter Syndrome (XXY)
- • Triple X syndrome (XXX)
-
FISH
use probes for a specific chromosomal region to determine how many copies of these 2 regions are present in cells
• no irreversible steps are taken because of FISH alone; findings are confirmed using karyotype
-
Edwards Syndrome (Trisomy 18)
- • 47, XX/XY, +18
- • small size
- • small head circumference
- • congenital heart defects
- • overlapping fingers (2nd over 3rd, 5th over 4th)
- • rocker bottom feet
- • very poor prognosis: only 5% survive after 1 year
-
What are the frequencies of live-born trisomies?
- • Down’s (21): 1 in 650-700
- • Edward’s (18): 1-2 in 6,000
- • Patau’s (13): 1-2 in 10,000
-
Down Syndrome (Trisomy 21)
- • 47, XX/XY, +21
- • flat facial profile
- • upslanted palpebral fissures
- • abnormal auricles (outer portion of ear overfolds)
- • nuchal skin fold (thickening of the skin around the neck)
- • single palmar crease
- • clinodactyly (pinkie finger curved)
- • hypotonia (floppy)
- • hyperflexibility of joints
- • widely spaced eyes
- • sandal toe gap
- • abnormal ears (low, posteriorly rotated)
-
Associated Findings of Down Syndrome
- • intellectual disability
- • congenital heart disease (AV valve)
- • GI abnormalities
- • atlantoaxial instability [excessive movement at the junction between the atlas (C1) & axis (C2)]
- • strabismus
- • thyroid abnormalities
- • leukemia
-
Patau Syndrome (Trisomy 13)
- • 47, XX/XY, +13
- • scalp defects (cutis aplasia, absence of skin)
- • microcephaly (small head)
- • microphthalmia: very small or poorly developed eyes
- • holoprosencephaly (embryo forebrain fails to develop into 2 hemispheres)
- • cleft lip (opening in the lip)
- • cleft palate (opening in the roof of the mouth)
- • CHD (heart defects)
- • polydactyly (extra fingers or toes)
- • renal abnormalities
- • very poor prognosis (only 5% survive 6 months)
-
Turner Syndrome
- • 45, X
- • lymphedema (puffy hands & feet) in infancy
- • heart abnormalities (bicuspid aortic valve, coarctation of aorta)
- • short stature (<150cm without="" growth="" hormone="" br="">• gonadal regression (streak ovaries)
- • low posterior hairline
- • webbed neck
- • widely-spaced hypoplastic (underdeveloped) nipples
- • horseshoe kidney
- • cubitus valgus of elbow (angled away from body)
-
Karyotypes in Turner Syndrome
- • 50%: 45,X
- • 46,abnormal X + X (eg. ring X)
- • mosaicism (eg. 45,X / 46,XY)
-
Klinefelter Syndrome (XXY)
- • tall stature, long limbs
- • learning disabilities
- • gynecomastia (after puberty)
- • small testicles
- • infertility (due to hypogonadism with oligospermia/azoospermia)
-
Triple X Syndrome (47,XXX)
- • speech delay
- • IQ 10-15 points below siblings
- • increased risk for infertility
- • most offspring are chromosomally normal
- • incidence: 1/1,000
-
47,XYY Males
- • IQ 10-15 points below siblings
- • may be at increased risk for behavioral problems - impulsivity & emotional immaturity
- • most offspring are chromosomally normal
-
What is “Counting” in reference to X-inactivation?
a mechanism to assess how many X-chromosomes are present because at least 1 must be active
-
What is “Choice” in reference to X-inactivation?
- • if both chromosomes are normal, choosing which will be inactivated is random
- • if a translocation occurs between an X chromosome & autosome, the normal X chromosome is inactivated to preserve autosomal material
- • if an unbalanced X translocation occurs, the abnormal X chromosome is inactivated
-
What will happen to an X chromosome if it has the XIST gene?
- • X with the XIST gene → inactivated
- • X without the XIST gene → stays active (will not be inactivated)
-
What is cis inactivation in reference to X-inactivation?
it refers to the fact that X-inactivation works so that the X inactivates itself – there is a cascade of activity that covers the chromosome reducing access to the DNA & shutting off the genes
• it spreads in both directions & the XIST locus in Xq13 is responsible for cis inactivation
-
What percentage of genes escape cis inactivation of the X chromosome?
~15%
-
Non-disjunction
failure of chromosomes or chromatids to separate & go to different daughter cells
• cells may undergo “trisomic rescue”
-
Trisomic Rescue
when a fertilized gamete with 3 copies of a chromosome loses 1 of these chromosomes to form a normal, diploid chromosome
• the copy of the chromosome most likely to be lost is from the parent who only gave ONE (uniparental disomy)
-
Heterodisomy
non-disjunction in meiosis I occurs, resulting in a parent passing on 1 copy of each homolog
-
Isodisomy
non-disjunction in meiosis II occurs, resulting in a parent passing ons 2 copies of the same chromosome
-
Triploidy
- • 3 copies of every chromosome, aka a gain of a whole set of 23 chromosomes (new number of chromosomes = 69)
- • most commonly caused by 2 sperm fertilizing 1 egg
- • is frequently seen in missed abortion material
-
Haploid (n)
half the normal chromosome number (23), what’s found in the gametes (1 copy of each chromosome)
-
Diploid (2n)
normal chromosome number of 46 (2 copies of each chromosome)
-
Polyploidy
- abnormality in number of all chromosomes
- • triploidy - having 3 full sets of chromosomes (69,XXY)
- • tetraploidy - having 4 full sets of chromosomes (92,XXYY)
-
Autosome
chromosomes 1 – 22 (non-sex chromosomes)
-
Monosomy
- loss of a chromosome, total number of chromosomes = 45
- • eg. Turner's Syndrome
-
Trisomy
gain of a chromosome; total number of chromosomes = 47
|
|
