One of the central problems in modern human genetics is to understand the functional impact of genetic variation. Of the millions of DNA positions that vary among humans, which sites actually impact human phenotypes and disease? It is becoming increasingly clear that noncoding variants that impact gene regulation play central roles in the genetics of disease. Yet we have limited understanding of the precise pathways by which these variants act, and it remains extremely difficult to predict which variants in the genome have regulatory effects. In this projec we propose to use detailed functional characterization of a variety of aspects of gene regulation, using 70 human lymphoblastoid cell lines as a model system, along with new computational methods, to dissect in detail the mechanisms by which genetic variation impacts gene expression levels.

Public Health Relevance

The purpose of this project is to improve our understanding of the mechanistic links between genetic variation and differences in gene regulation across individuals. This work will be valuable for interpreting disease association studies using resequencing and GWAS approaches.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
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Genomics, Computational Biology and Technology Study Section (GCAT)
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Senthil, Geetha
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University of Chicago
Schools of Medicine
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Simons, Yuval B; Turchin, Michael C; Pritchard, Jonathan K et al. (2014) The deleterious mutation load is insensitive to recent population history. Nat Genet 46:220-4
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