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.

项目概要迫切需要在小型、多样化的群体中进行群体基因组研究——允许遗传学家来描述任何人类群体疾病/表型的遗传决定因素。最近提出了多种新的复杂性状作图方法，用于内婚或然而，这些方法通常是针对特定的欧洲血统而开发的。考虑到的案例研究（例如在哈特派、撒丁岛）以及对替代群体的应用介绍了特殊的挑战，尤其是非洲大陆和非裔美国人。我的实验室专门研究非洲基因组多样性，我有超过 13 年的经验在南部非洲开发队列收集以测试有关遗传结构和的假设。非洲群体的多基因选择模式，我关注高度遗传、易于测量的性状 [例如身高、皮肤色素沉着]作为识别基因型-表型关联的模型系统。例如，我们已经证明，非洲人的色素沉着的多基因性要复杂得多虽然实地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机会。其他南部非洲人（例如 KhoeSan）的基因组资源包含遗传基因。在其他地方很少观察到的变异及其不寻常的连锁不平衡模式可以用于精细绘制因果变异图谱这笔资助的成果将包括：1) 收集 DNA，维护。实地考察并为我们的实验室描述南部非洲人群的基本基因组特征和合作者；2）使用估计南部非洲人的重组率和突变模式深厚的血统；3）使用皮肤色素沉着和身高作为模型来了解可移植性跨人群的基因型-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）

Predicting Environmental and Ecological Drivers of Human Population Structure.

预测人口结构的环境和生态驱动因素。

DOI：
发表时间：
2023-05-02
期刊：
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.

Khoe-San 的重组景观可能代表了人类重组分歧的上限。

DOI：
发表时间：
2022-08-09
期刊：
影响因子：
12.3
作者：
van Eeden, Gerald;Uren, Caitlin;Pless, Evlyn;Mastoras, Mira;van der Spuy, Gian D;Tromp, Gerard;Henn, Brenna M;Möller, Marlo
通讯作者：
Möller, Marlo

Persistence of Matrilocal Postmarital Residence Across Multiple Generations in Southern Africa.

南部非洲多代人婚后居住的持续存在。

DOI：
发表时间：
2023-06
期刊：
影响因子：
0
作者：
Reynolds, Austin W;Grote, Mark N;Myrick, Justin W;Al;Siford, Rebecca L;Mastoras, Mira;Möller, Marlo;Henn, Brenna M
通讯作者：
Henn, Brenna M

Chromosomal patterns of microsatellite variability contrast sharply in African and non-African populations of Drosophila melanogaster.

非洲和非非洲黑腹果蝇种群中微卫星变异的染色体模式形成鲜明对比。