Recent studies have indicated that human genetic variation has a """"""""haplotype block structure"""""""" such that each chromosome can be decomposed into large blocks with strong linkage disequilibrium (LD) and relatively few haplotypes, separated by short regions of extensive recombination. The primary objective of this application is to study the biological significance of the observed haplotype structure and the practical implications of such haplotype structure for the mapping of genes responsible for human disease. To achieve this objective, we take an inter-disciplinary approach involving molecular biologists, population geneticists, genetic epidemiologists, statisticians, computer scientists, and mathematicians. We achieve the objective through five inter-related specific aims: (1) Develop efficient algorithms to improve the accuracy of polymorphism detection by both DNA sequencing and hybridization chips; (2) Develop efficient computational algorithms for haplotype block partitions and tag SNP selection; (3) Investigate the correspondence between the observed blocks and experimentally determined (primarily through genotyping of single sperm) rates of recombination; (4) Explore population genetics models of haplotype evolution that include alternative reasons for the presence of haplotype structure; and (5) Study the implications of haplotype block structure for association studies of both quantitative and qualitative traits, and develop novel statistical methods for association studies based on haplotype structure. We will validate and apply the newly developed methods on data from a variety of sources, both public and private. In addition to the scientific aims, we will train scientists in interdisciplinary, quantitative approaches to analyzing genomic polymorphism data, and in bioinformatics more generally. The need for such training is clear. We have a strong record of training in computational biology, and believe that we can provide a unique learning environment.

Agency
National Institute of Health (NIH)
Institute
National Human Genome Research Institute (NHGRI)
Type
Specialized Center (P50)
Project #
1P50HG002790-01A1
Application #
6703439
Study Section
Ethical, Legal, Social Implications Review Committee (GNOM)
Program Officer
Brooks, Lisa
Project Start
2003-09-30
Project End
2008-08-31
Budget Start
2003-09-30
Budget End
2004-08-31
Support Year
1
Fiscal Year
2003
Total Cost
$3,513,797
Indirect Cost
Name
University of Southern California
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
072933393
City
Los Angeles
State
CA
Country
United States
Zip Code
90089
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
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
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
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
Horton, Matthew W; Willems, Glenda; Sasaki, Eriko et al. (2016) The genetic architecture of freezing tolerance varies across the range of Arabidopsis thaliana. Plant Cell Environ 39:2570-2579
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
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
Sasaki, Eriko; Zhang, Pei; Atwell, Susanna et al. (2015) ""Missing"" G x E Variation Controls Flowering Time in Arabidopsis thaliana. PLoS Genet 11:e1005597
Kurmangaliyev, Yerbol Z; Favorov, Alexander V; Osman, Noha M et al. (2015) Natural variation of gene models in Drosophila melanogaster. BMC Genomics 16:198
Ostrow, A Zachary; Viggiani, Christopher J; Aparicio, Jennifer G et al. (2015) ChIP-Seq to Analyze the Binding of Replication Proteins to Chromatin. Methods Mol Biol 1300:155-68

Showing the most recent 10 out of 164 publications