The explosion in gene mapping and sequence data during the past quarter century accompanied by enormous computational strides. Some of these advances merely reflect the rapid evolution of modern computers. Other advances involve substantial improvements in statistical models and numerical algorithms particular to genetics. If human geneticists are to extend their successes in cloning Mendelian disease genes to common diseases, it is imperative that mathematical scientists continue to design and develop better statistical methods and more efficient numerical algorithms. The present proposal addresses some of the computation and statistical issues occurring in pedigree analysis, haplotyping, non- parametric linkage analysis, disequilibrium mapping, radiation hybrids, population genetics, and molecular phylogeny. Common mathematical themes such as graph theory, hidden Markov chains, the EM algorithm optimization theory, and Monte Carlo sampling bind these disparate areas together. The mathematical and computational analogies are sufficiently strong that simultaneous progress an be made on several fronts of benefit to geneticists. Even after the human genome is completed sequenced, geneticists. will still be faced with the enormous challenges of mapping and cloning genes for common diseases. Finding the best populations to study and the best statistical methods to apply will require a better understanding of how disease genes evolve in populations. The burgeoning sequence data bases will also dramatically intensify the need for constructing evolutionary tress of non-human species. This proposal suggests several ambitious avenues for research in the above areas. Our intention is to pursue the most promising of these leads while keeping an opportunistic eye on new developments in genetics for additional problems. Production of usable software will be a natural outgrowth of our investigations.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM053275-08
Application #
6490090
Study Section
Genome Study Section (GNM)
Program Officer
Eckstrand, Irene A
Project Start
1995-08-01
Project End
2003-12-31
Budget Start
2002-01-01
Budget End
2002-12-31
Support Year
8
Fiscal Year
2002
Total Cost
$186,358
Indirect Cost
Name
University of California Los Angeles
Department
Biostatistics & Other Math Sci
Type
Schools of Medicine
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Lake, James A; Larsen, Joseph; Tran, Dan Thy et al. (2018) Uncovering the Genomic Origins of Life. Genome Biol Evol 10:1705-1714
vonHoldt, Bridgett M; Ji, Sarah S; Aardema, Matthew L et al. (2018) Activity of Genes with Functions in Human Williams-Beuren Syndrome Is Impacted by Mobile Element Insertions in the Gray Wolf Genome. Genome Biol Evol 10:1546-1553
Paul, Kimberly C; Sinsheimer, Janet S; Cockburn, Myles et al. (2018) NFE2L2, PPARGC1?, and pesticides and Parkinson's disease risk and progression. Mech Ageing Dev 173:1-8
Lin, Liang-Yu; Chun Chang, Sunny; O'Hearn, Jim et al. (2018) Systems Genetics Approach to Biomarker Discovery: GPNMB and Heart Failure in Mice and Humans. G3 (Bethesda) 8:3499-3506
Gilbert, Princess S; Wu, Jing; Simon, Margaret W et al. (2018) Filtering nucleotide sites by phylogenetic signal to noise ratio increases confidence in the Neoaves phylogeny generated from ultraconserved elements. Mol Phylogenet Evol 126:116-128
Shi, Huwenbo; Mancuso, Nicholas; Spendlove, Sarah et al. (2017) Local Genetic Correlation Gives Insights into the Shared Genetic Architecture of Complex Traits. Am J Hum Genet 101:737-751
Keys, Kevin L; Chen, Gary K; Lange, Kenneth (2017) Iterative hard thresholding for model selection in genome-wide association studies. Genet Epidemiol 41:756-768
Crandall, Carolyn J; Manson, JoAnn E; Hohensee, Chancellor et al. (2017) Association of genetic variation in the tachykinin receptor 3 locus with hot flashes and night sweats in the Women's Health Initiative Study. Menopause 24:252-261
Zhang, Yiwen; Zhou, Hua; Zhou, Jin et al. (2017) Regression Models For Multivariate Count Data. J Comput Graph Stat 26:1-13
Paul, Kimberly C; Sinsheimer, Janet S; Cockburn, Myles et al. (2017) Organophosphate pesticides and PON1 L55M in Parkinson's disease progression. Environ Int 107:75-81

Showing the most recent 10 out of 156 publications