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Leveraging genetic variation to understand chromosome pairing, meiosis and the evolution of human disease risk (360G-Wellcome-212284_Z_18_Z)

<p>We have the following specific aims:</p> <ol> <li>To discover how normal pairing (synapsis) of homologous chromosomes during mammalian meiosis is genetically controlled in fertile and infertile individuals, and how synapsis first initiates, and then spreads. To do this, we will leverage naturally occurring genetic variation. Errors in recombination, and in synapsis, result in aneuploidy events, and chromosomal rearrangements due to NAHR, that cause many human disorders including infertility, pregnancy loss, cancer, and developmental syndromes.</li> <li>To quantify how the chromatin accessibility and gene expression environments change during meiosis, using single-cell ATAC and RNA sequencing, and learn how proteins binding to DNA coordinate the onset and progression of meiosis, recombination, synapsis and impact fertility, and are impacted by genetic variation and chance.</li> <li>To build from our existing approaches to understand population structure, in order to infer trees revealing the historical relationships relating hundreds of thousands of modern and ancient individuals, in humans and other recombining species. We will use these trees, which change along the genome due to recombination, to investigate how variation impacting complex diseases and other traits has arisen and been acted upon by natural selection, how selection changes through time, and how the rate of evolution itself evolves through time.</li> </ol>

£1,579,531

17 Jul 2018

Grant details
Amount Awarded 1579531
Applicant Surname Myers
Approval Committee Science Interview Panel
Award Date 2018-07-17T00:00:00+00:00
Financial Year 2017/18
Grant Programme: Title Investigator Award in Science
Internal ID 212284/Z/18/Z
Lead Applicant Prof Simon Myers
Planned Dates: End Date 2023-09-12T00:00:00+00:00
Planned Dates: Start Date 2018-09-12T00:00:00+00:00
Recipient Org: Country United Kingdom
Region South East
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