In this supplement, we propose to extend our research to address a number of important and novel questions. We will use a novel whole genome sequencing dataset to reconstruct the demographic history of a number of ethnic groups in Cameroon including hunter-gatherers, pastoralists, and agriculturalists and will identify genomic targets of natural selection and associations with a number of adaptive traits. We hypothesize that many of these variants will in non-coding regions and play a role in gene regulation. We will use in vitro reporter assays and chromatin capture techniques to distinguish enhancer/promoter interactions. Lastly, we will extend our field work in Cameroon to study new populations including albinos from western, Central, and eastern Cameroon. We will collect new phenotype data including information about circadian rhythms, sleep wake cycles, and cardiac function. We will genotype these new samples for an African specific single nucleotide polymorphism (SNP) array and will impute variants not included in the array using our whole genome sequence data as reference genomes.

Public Health Relevance

We propose to perform field studies to collect novel biological samples and novel phenotypic data on anthropometric and metabolic traits in ethnically diverse populations from Cameroon and will genotype for an African-specific Single Nucleotide Polymorphism array. We will analyze whole genome sequence (WGS) data to infer demography and genomic targets of natural selection. We will integrate the WGS and SNP data to identify associations with a number of potentially adaptive complex traits. We will confirm functional regulatory variants using in vitro gene expression assays and will identify target genes using chromatin-capture techniques.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
3R01GM113657-04S1
Application #
9842091
Study Section
Program Officer
Janes, Daniel E
Project Start
2019-02-01
Project End
2020-01-31
Budget Start
2019-02-01
Budget End
2020-01-31
Support Year
4
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of Pennsylvania
Department
Genetics
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
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