20.04.15 Structural abnormalities of Y chromosome Flashcards
(38 cards)
What are the 3 unique features of Y chromosomes
- Lack of a homologous partner for crossing over
- Functional specialisation for spermatogenesis
- High degree of sequence amplification
How is Y chromosome useful for geneaology studies
Paternally inherited portion of the nonrecombining Y chromosome retains sequential records of the accumulation of genetic diversity over time
Why is it a difficult chromosome to analyse
- High density of repeated sequences makes physical mapping and sequencing difficult
- Does not recombine during meiosis so classical linkage mapping is not possible
Why is natural selection less effective in preventing the accumulation of deleterious mutations in the Y chromsome
- The lack of recombination.
- Results in genetic erosion of Y chromosome (will eventually become redundant in function)
What are the 3 azoospermia factor regions on Yq
AZFa, AZFb, AZFc
What proportion of Y chromosome is pesudoauatosomal region (1 and 2)
5%
What gives variability to Y chromosome length
- Variation in length of Yqh region (Yq12).
- Inactive heterochromatin.
- Size doesn’t have a phenotypic consequence
What is a pericentric inversion on Y chromsome
- Inversion that moves centromeric region to the heterochromatin border.
- No apparent effect on fertility or clinical significance.
- 1:200
How are sex vesicles formed
When X and Y chromosomes synapse at PARs during meiosis.
How prevalent are Y;autosome translocations
1:2000
Phenotypic consequences of Y;autosome translocations
-Male infertility, due to spermatogenic arrest.
What is the most prevalent Yq autosome translocation
- Acrocentric p arm and Yqh.
- 70% of Y autosome translocations.
- Most commonly t(Y;15), possibly due to homology of heterochromatin blocks of 15p and Yq. Also common= t(Y;22)
- Often familial and has no clinical significance, but could predispose to structural instabilities of Y or secondary chromosomal abnormalities.
Where is Yq-autosome breakpoints usually found
- Acrocentric= p11-13
- Y= Yq12
Can translocations occur between Yq and other autosomes (other than acrocentric p arms)
- Yes but rare.
- Usually balanced so seen with oligo/azoospermia, hypogonadism
- Phenotypic abnormalities occur if there is gene disruption at break points, positional effects or unbalanced
Review of autosome Yp translocations
- Can involve SRY translocation to an autosome (usually acrocentric)
- Phenotypically male with 45 chromosomes, 45,X
- 45,X,t(Y;15) could lead to PWS if breakpoints are at 15q11-q13
What is a dicentric Yp-acrocentric translocation
- P to P arm translocation
- 45 chromosome count
- Almost no genetic material is lost from either acrocentric or Y chromosome
- may be associated with oligospermia
What is the most common X;Y translocation
-46,X/Y, der(X) t(X;Y)(p22.3;q11)
How do X;Y translocation arise
- NAHR at spermatogenesis of female carrier’s father.
- NAHR between homologous genes (94% sequence similarity) PRKX and PRKY are implicated in 30% cases
What is a risk factor for X;Y translocations
Polymorphic paracentric inversion on Yq, placing PRKY in the same orientation as PRKX
Review of female 46,X,der(X)t(X;Y)
- Typically a fertile female of normal intelligence.
- Partial monosomy of Xp
- If SHOX is deleted then patient will have Leri-Weill dyschondrosteosis (skeletal dysplasia)
- 50% risk of transmitting der(X)
- XCI tends towards der(X) but can be variable
Review of male 46,Y,der(X)t(X;Y)
- Usually son of a der(X)t(X;Y) mother
- Partial nullisomy for Xp
- Infertile. Can be cognitively normal. If breakpoint is more proximaly and involves genes like MRX, then there is mental impairment.
What translocation accounts for most 46,XX males and some 45,X males
- Cryptic Xp;Yp translocation
- Loss of distal region of X chromosome and transfer of SRY
How is a cryptic Xp;Yp translocation detected
FISH.
Phenotypic consequences of a cryptic Xp;Yp translocation
- Males are infertile
- If loss of SHOX then leads to Leri-Weill dyschondrosteosis
