Lec 3: Numerical & Structural Abnormalities Flashcards
Aneuploidy
gain or loss of chromosomes equaling less than one complete complement
–not inherited but are due to meiotic or mitotic nondisjunction
Trisomy 2N+ 1 = 47
Eg. Trisomy 13: 47, XX, +13
Monosomy 2N–1 = 45
Eg. Monosomy 8: 45, XY, –8
Mosaic
45, X/46, XX
For numerical anomalies the total chrom # is increased or decreased and the specific chrom gained or lost would be noted at the end
eg: Trisomy 13, Monosomy 8
For sex anumerical anomalies no need to use + or – since the sign change in chrom complement is noted directly
eg: Monosomy X: 45,X
47, XXY, 47, XXX or 47, XXY are gains of sex chromosome
Trisomy 13 or Patau Syndrome
if a meiotic error produces a gamete with two copies of an A chromosome (A1 and A2), fertilization with a normal gamete (A5) will result in trisomy for the A chromosome (see image)
If the embryo begins with 46 chromosomes, what kind of error could give rise to some cells with 3 copies of chromosome 21. And the reciprocal product being monosomy 21
—-you have a gain of trisomy
a mitotic error
The reciprocal product, monosomy 21 would not be viable and would die out, leaving the disomy and trisomy cell lines.
If the embryo begins with Trisomy 21, a non-disjunction error could result in a disomic cell.
Here the reciprocal product is a tetrasomy which is nonviable. Again the final complement would be a mosaic with both disomic and trisomic cells.
Mosaicism
having two different cell lines with at least one celear variation between them
The numerical change in mosaicism could be
45, X and 46, XX
The structural change could be
one cell with a translocation that doesn’t occur in the other
Trisomy 21 (Downs Syndrome)
Trisomy 18 (Edwards Syndrome)
TrIsomy 13 (Patau’s Syndrome)
Sex Chromosome Aneuploidies
Kleinfelter, 47, XXY
XYY Male
XXX Female
Turner Syndrome: 45, X
What type of abnormality in XXX Female?
is usually due to maternal meiosis 1 error
What type of abnormality in XYY Male?
Failure of paternal meiosis (nondisjunction)
What is Kleinfelter Syndrome (47, XXY) and which sex does it describe?
it usually describes males
usually due to Meiosis 1 error in father
Turner Syndrome (45, X)
usually describes females
- usually due to meiotic nondisjunction
- due to a missing region of of the short arm of the X chromosome just proximal to the centromere
45,X/46,XY Mosaicism
these people may have male or female phenotype depending on which cells are active at the time of development
XY Female
- Y chromosome is intact and TDF functions.
- the TDF protein will initiate male development, but the pathway will be blocked at the point where the androgen receptor protein is required to form complex testosterone and dihydrotestosterone
- due to androgen sensitivity which is known as testicular feminization
- since this is not happening, further male differentiation is not possible and the phenotype will default to female.
XX Male
the pseudoautosomal region on the short arms of X and Y chromosomes pair and recombine during male meiosis
XX Male continued
the reciprocal translocation (TDF/SRY) is replaced by Xp material which is transmitted to a child) results in a Turner female phenotype with an apparent 46, XY karyotype.
XX male again
in a male with a balanced translocation there will be no clinical abnormalities, since the genes are all present, though in alternate locations.
if this male transmits the rearranged X chromosome to an offspring who has received an X from the mother, the resultant child will have an apparent XX chromosome complement. If the TDF/SRY is fully functional, he male developmental pathway will be triggered and a male or Kleinfelter male phenotype will occur
Structural Anomalies
Deletions, Duplication, Translocation and Inversion
