Population Genetics Methods for Understanding Complex Trait Evolution
理解复杂性状进化的群体遗传学方法
基本信息
- 批准号:10688263
- 负责人:
- 金额:$ 36.24万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-09-01 至 2027-08-31
- 项目状态:未结题
- 来源:
- 关键词:AccelerationAltitudeAreaComplexComputer softwareData SetDiseaseEvolutionGeneticGenetic VariationGenomeGenomic SegmentGenomicsHaplotypesHispanic Community Health Study/Study of LatinosHomozygoteHumanHuman GenomeIndividualKnowledgeLearningMacaca mulattaMedicalMethodologyMethodsModelingModernizationNatural SelectionsNaturePhenotypePopulationPopulation GeneticsPopulation ProcessProcessRecording of previous eventsResearchResourcesShapesStatistical MethodsTheoretical modelTrans-Omics for Precision MedicineVariantWorkbiobankdesigndisorder riskdiverse datagenetic architecturegenetic informationgenome sequencinggenomic datagenomic variationnovelpathogen exposurephenotypic dataprogramsstatisticstrait
项目摘要
Abstract
Understanding the genetic basis of complex phenotypes is a critical problem in medical and
evolutionary genetics. As the influx of rich genomic and phenotypic data accelerates via biobank-level
resources and reveals even greater fine scale genetic information, modern population genetic methods will be
critical to examine the influence of evolutionary processes on the distribution of complex traits.
My research in this area has focused on characterizing the effects of recent population history on the
distribution of deleterious variation in individuals and on the design and application of statistical methods for
the inference of positive selection in populations. Specifically, my work demonstrates that certain population
processes create concentrations of deleterious homozygotes in genomes and that the strength of
concentration depends on recent population history. This work reveals an important mechanism by which
population history can influence the genomics of complex traits. I have also contributed to methodological
advances for the identification of genomic regions undergoing positive selection, including designing novel
haplotype summary statistics, novel likelihood statistics that account for spatial autocorrelation in genomes,
and efficient software implementing this work which has been cited hundreds of times. I have applied these
and other methods to human and non-human genomic data, uncovering the genomic basis of adaptation to
pathogen exposure in different human populations and the polygenic nature of adaptation to high altitude in
rhesus macaques.
During the next five years, and beyond, my research will focus on identifying how evolutionary forces
shape the phenotypic landscape of modern humans and on developing uses for our knowledge of human
history to learn the genetic basis of complex traits. To this end, I will develop novel methods for the inference of
natural selection in genomes, I will develop theoretical models that connect evolutionary history to variation of
complex traits via its effect on the distribution of non-neutral genetic variation, and I will develop novel
statistical methods that leverage evolutionary information to identify genomic variation associated with traits.
This work will incorporate varying models of dominance, of genetic architecture, and of genetic overlap among
two or more traits. I will apply these models and methods to human whole-genome sequencing data sets
paired with biomedical phenotype data from diverse human populations with their own distinct histories, using
biobank resources such as the Trans-Omics for Precision Medicine program and the Hispanic Community
Health Study / Study of Latinos. My work in these areas will disentangle the relative influences of various
evolutionary processes that contribute to differences in complex traits, including disease risk, among
populations and will expand our understanding of the genetic basis of these traits in understudied populations.
摘要
项目成果
期刊论文数量(3)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
selscan 2.0: scanning for sweeps in unphased data.
- DOI:10.1093/bioinformatics/btae006
- 发表时间:2024-01-02
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
A genetic and linguistic analysis of the admixture histories of the islands of Cabo Verde.
- DOI:10.7554/elife.79827
- 发表时间:2023-04-25
- 期刊:
- 影响因子:7.7
- 作者:Laurent R;Szpiech ZA;da Costa SS;Thouzeau V;Fortes-Lima CA;Dessarps-Freichey F;Lémée L;Utgé J;Rosenberg NA;Baptista M;Verdu P
- 通讯作者:Verdu P
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