This proposal for the NIH Director's Early Independence Award is designed to realize the promise of genomics for improving health of all people by achieving a more complete understanding of the global architecture of human genomic diversity. This will be achieved by characterization global genomic diversity, including sequence and structural variation, in the context of the demographic history of human populations. To achieve this objected we propose three specific aims: (1) improve description of human demographic history and global diversity, (2) assess impact of demographic history on functional variation and inferences of archaic contributions to human variation and (3) develop methods to genotype genomic structural variation using short-read sequencing. The proposed research will provide essential information concerning the global prevalence and characteristics of under-ascertained variant types, clarify important characteristics of human population history, and define the lasting effects of this history on variation that is relevant for extant populations, including admixed or cosmopolitan populations whose genomes include segments from diverse continental ancestries. Understanding these global patterns of diversity, including sequence and structural variants, will be critical for proper execution and interpretation of studies designed to elucidate the genetic basis for disease susceptibility in diverse human populations.
Some genetic variants play an important role in altering susceptibility to human disease. These variants include both changes to the sequence and to the structure of genomes, and are known to vary across global populations. A more comprehensive understanding the nature of global patterns of genetic diversity will aid researchers in the identification of genetic variants relevant to disease risk in populations today.
|Zhao, Xuefang; Emery, Sarah B; Myers, Bridget et al. (2016) Resolving complex structural genomic rearrangements using a randomized approach. Genome Biol 17:126|
|Wildschutte, Julia Halo; Williams, Zachary H; Montesion, Meagan et al. (2016) Discovery of unfixed endogenous retrovirus insertions in diverse human populations. Proc Natl Acad Sci U S A 113:E2326-34|
|Oetjens, Matthew T; Shen, Feichen; Emery, Sarah B et al. (2016) Y-Chromosome Structural Diversity in the Bonobo and Chimpanzee Lineages. Genome Biol Evol 8:2231-40|
|Henn, Brenna M; BotiguÃ©, Laura R; Peischl, Stephan et al. (2016) Distance from sub-Saharan Africa predicts mutational load in diverse human genomes. Proc Natl Acad Sci U S A 113:E440-9|
|1000 Genomes Project Consortium; Auton, Adam; Brooks, Lisa D et al. (2015) A global reference for human genetic variation. Nature 526:68-74|
|Wildschutte, Julia H; Baron, Alayna; Diroff, Nicolette M et al. (2015) Discovery and characterization of Alu repeat sequences via precise local read assembly. Nucleic Acids Res 43:10292-307|
|Kidd, Jeffrey M; Sharpton, Thomas J; Bobo, Dean et al. (2014) Exome capture from saliva produces high quality genomic and metagenomic data. BMC Genomics 15:262|
|Dayama, Gargi; Emery, Sarah B; Kidd, Jeffrey M et al. (2014) The genomic landscape of polymorphic human nuclear mitochondrial insertions. Nucleic Acids Res 42:12640-9|
|Martin, Alicia R; Costa, Helio A; Lappalainen, Tuuli et al. (2014) Transcriptome sequencing from diverse human populations reveals differentiated regulatory architecture. PLoS Genet 10:e1004549|
|Poznik, G David; Henn, Brenna M; Yee, Muh-Ching et al. (2013) Sequencing Y chromosomes resolves discrepancy in time to common ancestor of males versus females. Science 341:562-5|