This proposal is for the renewal of our existing Center of Excellence in Genomic Science (""""""""Implication of Haplotype Structure in the Human Genome""""""""). Since the start of our Center in 2003, there have been extraordinary advance in genomics. Genome-wide association studies using Single Nucleotide Polymorphisms are now routine, and we are rapidly moving toward having whole-genome sequence data for large samples of individuals. Our Center has undergone similar dramatic change. While the underlying theme of our proposal remains the same - making sense of genetic variation - our focus is now explicitly on how we can use the heterogeneous data produced by modern genomics to achieve such an understanding. The overall goal of our proposal is to develop an intellectual framework, together with computational and statistical analysis tools, for illuminating the path from genotype to phenotype, and for predicting the latter from the former. We will address three broad questions related to this problem: 1) How do we infer mechanisms by which genetic variation leads to changes in phenotype? 2) How do we improve the design, understanding and interpretation of association studies by exploiting prior information? 3) How do we identify general principles about the genotype-phenotype map? We will approach these questions through a series of interrelated projects that combine computational and experimental methods, and involve a wide range of researchers including molecular biologists, population geneticists, genetic epidemiologists, statisticians, computer scientists, and mathematicians.

Public Health Relevance

- One of the most important challenges facing biology today is understanding how genetic variation between individuals translates (or maps) into variation we can see or measure, like blood pressure, and how this mapping is affected by the environment. The goal of this project is to increase our understanding of the general principles that underlie the genotype-phenotype map by studying model organisms.

National Institute of Health (NIH)
National Human Genome Research Institute (NHGRI)
Specialized Center (P50)
Project #
Application #
Study Section
Special Emphasis Panel (ZHG1-HGR-N (J1))
Program Officer
Brooks, Lisa
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Southern California
Biostatistics & Other Math Sci
Schools of Arts and Sciences
Los Angeles
United States
Zip Code
Signor, Sarah A; Abbasi, Mohammad; Marjoram, Paul et al. (2017) Social effects for locomotion vary between environments in Drosophila melanogaster females. Evolution 71:1765-1775
Rabanal, Fernando A; Mandáková, Terezie; Soto-Jiménez, Luz M et al. (2017) Epistatic and allelic interactions control expression of ribosomal RNA gene clusters in Arabidopsis thaliana. Genome Biol 18:75
Ostrow, A Zachary; Kalhor, Reza; Gan, Yan et al. (2017) Conserved forkhead dimerization motif controls DNA replication timing and spatial organization of chromosomes in S. cerevisiae. Proc Natl Acad Sci U S A 114:E2411-E2419
Peace, Jared M; Villwock, Sandra K; Zeytounian, John L et al. (2016) Quantitative BrdU immunoprecipitation method demonstrates that Fkh1 and Fkh2 are rate-limiting activators of replication origins that reprogram replication timing in G1 phase. Genome Res 26:365-75
Ren, Jie; Song, Kai; Deng, Minghua et al. (2016) Inference of Markovian properties of molecular sequences from NGS data and applications to comparative genomics. Bioinformatics 32:993-1000
Fear, Justin M; León-Novelo, Luis G; Morse, Alison M et al. (2016) Buffering of Genetic Regulatory Networks in Drosophila melanogaster. Genetics 203:1177-90
Chen, Quan; Zhou, Xianghong J; Sun, Fengzhu (2015) Finding genetic overlaps among diseases based on ranked gene lists. J Comput Biol 22:111-23
Fear, Justin M; Arbeitman, Michelle N; Salomon, Matthew P et al. (2015) The Wright stuff: reimagining path analysis reveals novel components of the sex determination hierarchy in Drosophila melanogaster. BMC Syst Biol 9:53
Kurmangaliyev, Yerbol Z; Ali, Sammi; Nuzhdin, Sergey V (2015) Genetic Determinants of RNA Editing Levels of ADAR Targets in Drosophila melanogaster. G3 (Bethesda) 6:391-6
Sasaki, Eriko; Zhang, Pei; Atwell, Susanna et al. (2015) ""Missing"" G x E Variation Controls Flowering Time in Arabidopsis thaliana. PLoS Genet 11:e1005597

Showing the most recent 10 out of 163 publications