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NIHNATIONAL HUMAN GENOME RESEARCH INSTITUTER01

EDGE CMT: deleterious recessive variation - from experimental data to predictive models

Completed
Institution
New York University, NY
Principal investigator
Matthew Rockman
Funding
$333K
Duration
2023–2026
Open portfolio

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Abstract

In population samples, segregating recessive variants at low frequency are largely inaccessible to study. This project uses an experimental system in which rare alleles have been made common, recessive alleles can be homozygosed on demand, and cumulative effects of large numbers of small-effect variants can be measured in an unbiased way. The project centers on the nematode Caenorhabditis becei, which has all the experimental virtues of C. elegans but with a mating system and population biology that make it better suited to questions about genetic diversity in general and recessive variation in particular. This project will measure sex-specific competitive fitnesses and sex- and allele-specific transcript abundances in a specially designed panel of C. becei to reveal the architecture of segregating recessive variation and its molecular characteristics. The data will address basic questions in evolutionary biology while generating generalizable gene- and variant-scale models that predict whether variants are likely to have recessive effects.

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R01NATIONAL HUMAN GENOME RESEARCH INSTITUTEZHG1-HGR-P(O2)allelesvariationvariantslow frequencyrecessiveproject centersproject measureallele-specific

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