Last Morning's talks

Last morning talks


I didn't have time to edit these, so here are my notes directly as I jot them down:

An excellent talk by Prezeworski
Looking for recombination events in order to determine whether males are more
data for 728 meioses with many more markers than
own heuristic approach to call markers
to infer recombination events in the father, from pedigree data
cummulative genetics
resolution at which could resolve crossover eventsm 24K crossover
hotspots id'd in analyses of LD (hapmap)
enrichment of crossover events in hotspots
also estimated the fraction of crossovers
looking at hotspots
no diff in the mean of "use of hotspots" between male and female
looked at LRT null: significnbt variation among individuals using a likelihood ratio test
how heritable is this hotspot usage? (given the known pedigree of the individuals)
so individuals are varying significantly in their use of hotspots, and that variation is heritable.
a similar proportion of crossover events occur in hotspots in males and females genome wide
along the genome, there is extensive variation in cross-pver rates at fine scales, supporting inferences based on analyses of LD.

this could in part explain the diff in hotspots btwn chimpanzee and human.

Used the same data to infer constraints on recombination rate in humans.
it's thought that at least one crossover per chr arm is necessary to ensure proper disjunction.
interesting if look at Lenzi et al. female meiosis is error prone. This analysis is impt for evol bio and human genetics.
How often does proper disjunction occur per gamete among viable individuals.
Modeled the distribution of no of crossover events on each chromosome

find that the proper disjunction can occur in the absence of any crossovers on a chromosome.
how strong would chromatid interference have to be to explain this?
alternatively,
is there a back up mechanism in humans as there is in Drosophila?
There's no known affect on relationship of paternal age and no of recombination events
viable offspring of older mothers have more crossover events; Possibly to overcome insults to the meiotic exchange over the 35-40 years of female's lifespan.

Dan Neafsey talked about widespread selection and frequent recombination in the genome of the Plasmodium falciparum malaria parasite
genetic diversity drives this disease: immune evasion, drug resistance, vaccine failure.
tackling diversity
112K known SNPs
1 snp per 200 bp
trying to capitalize on known snps
SNP avg call rate 91%
avg accuracy 91% and good call rate across samples
Showed that there is a geographic population structure (at the continent and sub-continent level)
ML, HKY+ gamma
LD reflects the local epidemiology
plotted LD for the different continental populations: senegal, thailand, brazil
LD up to 100Kb in brazil vs. much lower in senegal- suggesting a different effective population size
incidence of mult infections is highest senegal (more than one genotypic variety)
while recombination rate doesn't vary, outcrossing does since outcrossing requires multiply-infected hosts (mosquitos often only bites one, so not likely to happen there).

selection: pattern of divergence universal pattern. nonsyn > silent
selection is impacting the
freq in the spectrum isn't biasing nonsynonymous vs silent divergence (mapped avg DAF against proportion of SNPs with signiical Fst (P<0.05))
so what's the role of selection in this pattern?
patterns of div within populations (as opposed to btwn pop)
patterns indicates negative selection
purifying selection comes from derived allele frequencies (mapped for Senegal and Thailand) snp population frequence relative to percent of SNPs)
selective sweeps interrupted by crossover events
3 of 33 strains exhibit ancestral allele
but we also know that positive selection plays a role, too
selective sweeps are detectable
looked at the pfcrt locus, saw disparity as expected.
cq resistant
high diversity regions of the genome a
decoupling : (ie, reduced divergence in high diversity regions)
thinks this is the result of balancing selection: retarding divergence
malaria SNP diversity influenced by pos and neg sel
LD is short, del on local epidemiology
new genotyping tools, 75K SNP genotyping array and Taqman molecular barcode.
Jeffares asked if Neafsey is looking for conservative vs radical aa changes, as well as looking for functional enrichment along selection profile.

Then was a talk about the 17q21.31 microdeletion syndrome (see Genome Research May, 2008)
these events are deNovo, estimated that 1% unexplained mental retardation is probably related to this microdeletion.
All the cases identified so far has been european
The inversion is under pos selection; ind which carry polymorphism show inc fecundity and global recombination
relationship btween microdel and inversion?
tested 17 parents of children
looked for the inversion in non human primates using FSH.
They estimated a human duplicated gene inversion toggling
inverted H2 haplotype most likely represents the ancestral state of huymans
inversions represent a premutation state for large scale de novo microdeletion and disease, maybe because of structural variation of segmental duplications favors NAHR.
(all this in Kidd, Nature 2008)

In all, the meeting was VERY informative. Many posters were also worth looking at. I will have the abstract book available in the computational lab.