Dear all,
just a gentle reminder the next seminar will take place this Wednesday,
the details are below. We look forward to seeing you all.
Best wishes,
Petr Danecek
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Title: Investigating the Genetics of Sexual Reproduction in 200,000 Humans
Speaker: Eugene Gardner
Date and time: *Wednesday 23/03/2022 - 17:20
*Location: MFF UK, Malostranské nám. 25*, lecture hall S9 **
*
Abstract:Why genes in the human genome are under significant constraint
remains a mystery. New genetic variants arise in the germline due to
mutation. While the majority are genetically neutral and have no effect
on phenotype, some variants confer either an advantage and proceed
towards fixation via positive selection, or a disadvantage and are
removed from the gene pool by negative selection. The context of where a
given variant arises in the genome strongly predicts whether it is
eliminated or becomes fixed, with the function of the gene impacted
among the most predictive for coding variation. Genes that are depleted
of deleterious genetic variation (DGV) due to negative selection are
said to be “constrained”. Depending on the method of calculation and
dataset used, the human genome contains ~3,000 such genes. While genes
associated with dominant diseases such as developmental disorders are
among the most constrained genes in the human genome, well-characterised
gene-disease pairs only comprise ~35% of all genes determined to be
under significant constraint. Based on the principles of evolution, it
can be assumed that natural selection shapes genic constraint by
reducing an individual’s ability to pass on their genes via sexual
reproduction. As part of recent work, using sequencing data for 200,000
humans from the UK Biobank Study, we have shown that genetic variants
that damage these genes are associated with markedly reduced
reproductive success, primarily due to increased childlessness, with a
stronger effect in males than in females. We provided evidence that
increased childlessness is likely mediated by genetically associated
cognitive and behavioural traits, which may mean male carriers are less
likely to find reproductive partners. This reduction in reproductive
success may account for 20% of purifying selection against heterozygous
variants that ablate protein-coding genes. While this genetic
association could only account for a very minor fraction of the overall
likelihood of being childless (less than 1%), especially when compared
to more influential sociodemographic factors, it may influence how genes
evolve over time.