Chromosome Number Flashcards
Why does Trisomy 21 occur more frequently in young mothers?
Young mothers have more babies than older mothers– even though the risk is smaller DS has a higher prevalence in this age group
What form of chromosomes are targeted in a slide preparation for FISH?
Metaphase or interphase
Test that applies a specific probe in order to determine the number of copies of chromosome present
FISH
How does a fluorescent probe join DNA?
DNA is denatured and hybridized with complementary probe
FISH analysis can determine…
if the probed chromosomes are numerically correct
FISH analysis cannot determine…
if anything is wrong with unprobed regions of the genome nor if mosaicism is present
Mitotic nondisjunction creates presence of more than one cell line
Mosaicism
Mosaicism
Mitotic nondisjunction creates presence of more than one cell line
What is the most plausible cause of trisomy mosaicism?
Normal cell line at conception, then a nondisjunction event gave rise to an additional chromosome
Always results from post-zygotic error
mosaicism
Possible locations of mosaicism
Generalized, confined to placenta, confined to fetus
What limits diagnosis of mosaicism?
Limitations in sampling, which includes tissue specific differences
Level of mosaicism correlates with
phenotypic severity
Which tissues often contain trisomic cells?
Kidney, placenta, gut
Nondisjunction
error in cell division in which improper segregation results in abn chromosome number
Error in this leads to mosaicism
mitosis
Which portion of cell division has an age-related risk of maternal nondisjunction?
Meiosis I
How many normal daughter cells result for meiosis I nondisjunction?
0
How many normal daughter cells result for meiosis II nondisjunction?
2
Euploid
normal chromosome number
Aneuploidy
abnormal chromosome number
Polyploidy
Additional set of chromosomes
Most common cause of triploidy
Dispermy
Cause of tetraploidy
Failure of cell division
T/F: ALL monosomies are lethal
T
Trisomies than can result in a live birth
- 18, 21, Sex chromosomes
How does mosaicism affect the severity of a trisomy?
The normal chromosomes make the phenotype less severe
Including preimplantation errors, how many fertilized eggs spontaneously abort?
50%
Common sex chromosome abnormality, frequently results in spontaneous ab
45, X
Why do monosonies reflect such a small portion of observed spontaneous abortions?
They abort so early detection is uncommon.
Why does the risk of a trisomy 21 offspring decrease as the pregnancy develops?
Spontaneous abortions
Phenotypic result of 47,XXX 47,XXY or 47XYY
Pretty minor problems with a normal lifespan
Common phenotypic characteristics of Down Syndrome
heart defects, simian crease, MR, duodenal atresia (obstruction)
Most common cause of trisomy 21?
Meiosis I nondisjunction
Trisomy 21 mosaicism is (more/less) severe than a purely trisomic genome
Less
Common phenotypic characteristics of trisomy 18
Clutched hands, rocker bottom feet, MR, heart defect
Common phenotypic characteristics of trisomy 13
Midline defects (cleft palate, eyes close-set or fused), forebrain fails to form lobes, MR, abdominal defects, polydactyly
Common causes of trisomy 13
Maternal meiosis nondisjunction > Robertsonian
Why are extra copies of X tolerated?
All but one is inactivated
Common phenotypic characteristics of Turner Syndrome
Ovarian dysgenesis, amenorrhea, infertility, abn lymphatics, no MR, neck webbing
Result of X chromosome nullisomy
Non-viable
Only tolerated monosomic condition
45,X (still has a high rate of miscarriage)
Most likely cause of Turner’s Syndrome.
Paternal meiotic nondisjunction (no relation to advanced maternal age)
What may contribute to the high survival rate of Turner’s Syndrome genotype?
Mosaicism
Possible genotypes of mosaic Turner’s Syndrome
45,x/47,XXX or 45,X/46,XX or 45,X/46,XY
Genotype of Klinefelter’s Syndrome
47,XXY
Common causes of Klinefelter’s Syndrome
50% Paternal nondisjunction, 50% age-related maternal nondisjunction
Common phenotypes in Klinefelter’s Syndrome
hypogonadism, long extremities, reduced IQ, gynecomastia
Most common cause of Triple X Syndrome
Maternal nondisjunction, related to age
Phenotypic results of Triple X Syndrome
essentially normal
Cause of 47,XXY Syndrome
Paternal meiosis II nondisjunction without age effect
