Administrative Supplement: Improving Inference of Genetic Architecture and Selection with African Genomes

行政补充：利用非洲基因组改进遗传结构的推断和选择

基本信息

批准号：
10891050
负责人：
Brenna M Henn
金额：
$ 11.16万
依托单位：
UNIVERSITY OF CALIFORNIA AT DAVIS
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-08-01 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10891050
关键词：
Address Administrative Supplement Africa African African American population Alleles Area Asian population Basic Science Biological Models Biomedical Research Body mass index Botswana Candidate Disease Gene Case Study Clinic Collection Communities Complex DNA Data Data Set Databases Disease Ethiopia European Evolution Forensic Medicine Frequencies Genes Genetic Genetic Determinism Genetic Load Genetic Recombination Genetic Variation Genome Genomics Genotype Goals Grant Haplotypes Height Heritability Human Human Genetics Individual Maps Measures Methods Methylation Mind Modeling Mutate Mutation Namibia National Institute of General Medical Sciences Nurses Outcome Pattern Phenotype Pigmentation physiologic function Population Population Genetics Population Heterogeneity Predisposition Recontacts Research Research Assistant Resolution Resources Sample Size Sampling Sickle Cell Site Skin Pigmentation South Africa Southern Africa Speed System Testing Tuberculosis Universities Variant Weight Withdrawal Work causal variant cohort community engagement comparative experience genetic analysis genetic architecture genetic pedigree genetic selection genetic variant genome resource genome wide association study hutterite improved large datasets portability programs reconstruction recruit reference genome rural health clinic segregation success trait

项目摘要

Project Summary There is a pressing need for population genomic research in small, diverse cohorts -- allowing geneticists to characterize the genetic determinants of disease/phenotype for any human community. A variety of new complex trait mapping methods have been recently proposed for endogamous or admixed populations. However, these methods were often developed with specific European-descent case-studies in mind (e.g. in Hutterites, Sardinians) and application to alternative cohorts introduces special challenges, especially in continental African and African-American populations. My lab specializes in African genomic diversity and I have over 13 years experience developing cohort collections in southern Africa. To test hypotheses about genetic architecture and polygenic selection patterns in African cohorts, I focus on highly heritable, easily measured traits [e.g. height, skin pigmentation] as model systems for identifying genotype-phenotype associations. We have shown, for example, that the polygenicity of pigmentation is far more complex in Africans than in Europeans. While field work is central to my lab’s research program, it also provides a crucial genomic resource for other research groups. Southern Africans, like the KhoeSan, contain genetic variants which are rarely observed elsewhere and their unusual patterns of linkage disequilbrium can be used to fine-map causal variants. Outcomes of this grant will include: 1) collect DNA, maintain field sites and characterize fundamental genomic features of southern African populations for our lab and collaborators; 2) estimate recombination rates and mutational patterns in southern Africans using deep pedigrees; 3) use skin pigmentation and height as models for understanding the portability of genotype-phenotype associations across populations.

项目摘要在小型，潜水员队列中对人群基因组研究的迫切需求 - 允许遗传学家表征任何人类疾病/表型的遗传决定者。最近已经提出了各种新的复杂性状映射方法，以进行内属或混合种群。但是，这些方法通常是通过特定的欧洲味开发的考虑案例研究（例如，在Hutterites，Sardinians）和替代人群中的应用介绍特别挑战，特别是在连续的非洲和非裔美国人人口中。我的实验室专门从事非洲基因组多样性，我拥有13年以上的经验在南非开发队列收藏。测试有关遗传结构和的假设在非洲队列中的多基因选择模式，我专注于高度可遗传的，易于测量的特征 [例如。高度，皮肤色素沉着]作为识别基因型 - 表型关联的模型系统。例如，我们表明，在非洲人中，色素沉着的多基因更为复杂比欧洲人。虽然现场工作是我实验室研究计划的核心，但它也提供了至关重要的其他研究小组的基因组资源。南部非洲人，像Khoesan一样，都包含遗传很少在其他地方观察到的变体及其异常的连锁不平衡模式可以用于微图因果变体。这笔赠款的结果将包括：1）收集DNA，维护现场站点和我们实验室的南非人群的基本基因组特征和合作者； 2）使用南部非洲人的重组率和突变模式使用深部族； 3）使用皮肤色素沉着和高度作为了解可移植性的模型人群之间的基因型 - 表型关联。

项目成果

期刊论文数量（9）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Genetic differentiation at probe SNPs leads to spurious results in meQTL discovery.

DOI：
10.1038/s42003-023-05658-5
发表时间：
2023-12-21
期刊：
COMMUNICATIONS BIOLOGY
影响因子：
5.9
作者：
Meeks, Gillian L.;Henn, Brenna M.;Gopalan, Shyamalika
通讯作者：
Gopalan, Shyamalika

Predicting Environmental and Ecological Drivers of Human Population Structure.

DOI：
10.1093/molbev/msad094
发表时间：
2023-05-02
期刊：
MOLECULAR BIOLOGY AND EVOLUTION
影响因子：
10.7
作者：
Pless, Evlyn;Eckburg, Anders M.;Henn, Brenna M.
通讯作者：
Henn, Brenna M.

The recombination landscape of the Khoe-San likely represents the upper limits of recombination divergence in humans.

DOI：
10.1186/s13059-022-02744-5
发表时间：
2022-08-09
期刊：
Genome biology
影响因子：
12.3
作者：
通讯作者：

Increased homozygosity due to endogamy results in fitness consequences in a human population.

由于内婚导致的纯合性增加导致了人群的健康后果。

DOI：
10.1073/pnas.2309552120
发表时间：
2023-10-24
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
影响因子：
11.1
作者：
Swinford, N. A.;Prall, S. P.;Gopalan, S.;Williams, C. M.;Sheehama, J.;Scelza, B. A.;Henn, B. M.
通讯作者：
Henn, B. M.

Inferring Recombination Patterns In African Populations.