Sex Recombination Flashcards
What are the 4 main consequences of sex?
More likely for a child to inherit a mutation from the father
Recombination occurs at a higher rate in female germline
Allele specific expression (imprinting)
Differential expression of X-linked disease alleles
What are the main differences between theX and Y chromosomes and how did they first appear?
X = 1000 genes Y = 78 and most of the long arm is heterochromatic
Evolution of sex chromosomes occured multiple times e.g. bird W and Z have independant origin. Starts with maleness gene on an autosome that is protected from recombination - termed the non recombining Y. Over time this expands to include more DNA due to segmental inversions. for example PAR2.
Why is a child more likely to have a mutation from their father?
Using linkage studies it was shown that children are more likely to have de novo mutations from the father. extreme example being achondroplasia where all mutations are always from the father. Also age effect - more from older fathers.
This is because many more replications take place in the male germline and so many more mutations occur. But this doesn’t fully account for the increased mutations rate.
Normally division is asymmetric in spermatogenesis. But if a mutation occurs that influences signalling and growth then you can get clonal expansion and symmetric division. This results in selected for new mutations.
Genome wide analysis reveals that substitutions and microsatellite mutations are more likely to be from father, but there is an age effect in mothers too.
What is the function of recombination?
Genetic diversity
Provision of tension between chromosomes allowing segregation.
What are the two main reasons we would expect regions of homology between the X and Y chromsome?
Ancestral relationship - used to be autosomes.
Need recombination events to provide tension for appropriate segregation.
Most examples of 47XXY show no recombination in PAR1 - normally X and Y form a synaptonemal complex in PAR1 on the short arm of Y
How does recombination change along the Y chromsome’s PAR1 region?
At telomeres recombination is obligatory in males and 7% in females (still much higher than normal). This level decreases as you approach the sex specific DNA of the Y.
This was shown through variable linkage of polymorphisms. where obligatory recombination occurs it is 50:50 which chromosomes the marker is seen on.
What is different about PAR2 compared to PAR1?
There is no obligatory recombinaton event bu there is still an elevated amount over the genome average. In other primates PAR2 is sex specific to X showing it has recently moved to Y in humans. PAR2 only has 4 genes.
How does recombination differ in the autosomes and X chromsomes between men and women?
Autosomes - females have a higher rate of recombination that men due to the activity of recombination hotspots differing between the two sexes.
X chromsomes in females act just like autosomes
X chrome in males only show recombination i PAR1 and 2 regions at the tips of chromosomes.
Why does recombination differ between males and females?
Recombiantion occurs in jungles and doesn’t occur in deserts.
70% of male jungles occurs in the 5% more telomeric DNA of chromosomes whilst in females it is only 18%. The reason for this is recombination occurs at axial loops due to PRDM9. In females these loops are longer and so when recombination occurs this spans a longer distance of DNA = high rate of recombination.
Describe the important parts of oogenes in relation to non disjunction.
Downsyndrome is the leading cause of fetal death in humans. Aneuploidy occurs 10-30% of the time in human fertilized eggs but only 1-2% in mice. Mostly occurs in female germline.
Most of M1 occurs during foetal development including synapsis and crossing-over but then maintained in prolonged diplotene state. Segregation of the chromosomes is delayed during MI and MII until ovulation and fertilisation.
How does Trisomy 21 occur as a result of oogenesis?
The recombination events are poorly placed and there is a vulnerability with age.
Comparing genetic maps of down syndrome patients and looking at centromere markers to identify which meiosis the event occured in.
85% of non disjunction occurs in Meiosis 1 due to recombination events being too distal and so prone to loss of chiasmata before spindle attatchment.
Other 15% occurs in meiosis 2 this is usually because of recombination closer to the centromere and result in entanglement of the homologes. Actually a meiosis 1 event that is resolved in meiosis 2.
Normally cohesins hold sister chromatids together, in anaphase 1 they are lost on the arms to allow homologous chromosomes to separate. Shugoshin protects them at the centromere. In anaphase 2 thiscomplex break and allow the seperation of the sister chromatids. Cohesin rings established in utero but not replenished hence age effect.
Are the reasons for trisomies in other chromosomes similar?
Yes but they effect each differently. Also the meiotic checkpoints in females are far less stringent than in males.
