Leonard McMillan & Wei Wang
Computational Tools for Systems Genetics
We are focusing on two projects within the Center:
We are constructing a database to host the genotyping, transcript, copy-number variation, and methylation data for Center projects, and external users of the Mouse Diversity Genotyping array. This database will serve as a primary data repository warehousing the Centerís experimental results. It will also serve as a portal to provide public access to the results of expensive analysis and mining tasks in the future. In this project we are exploiting underutilized capabilities of modern database management systems such as the active database and temporal database technologies.
Genome Compatibility and Tree-based Association Analysis
We are developing efficient methods for partitioning genomes into parsimonious sets of compatible intervals. Our algorithms aim to find every possible haplotype interval without any apparent recombination or homoplasy on a genome-wide scale. We are identifying a subset of single nucleotide polymorphisms whose removal might reduce the number of intervals necessary to cover all markers. Each genomic region has a unique phylogenetic tree describing relatedness of haplotypes in the region. Given a set of local phylogeny trees spanning the entire genome, we are using these trees as high-level markers for primary phenotype association mapping.
Center related publications
Genetic analysis of complex traits in the emerging collaborative cross
Aylor DL, Valdar W, Foulds-Mathes W, Buus RJ, Verdugo RA, Baric RS, Ferris MT, Frelinger JA, Heise M, Frieman MB, Gralinski LE, Bell TA, Didion JD, Hua K, Nehrenberg DL, Powell CL, Steigerwalt J, Xie Y, Kelada SN, Collins FS, Yang IV, Schwartz DA, Branstetter LA, Chesler EJ, Miller DR, Spence J, Liu EY, McMillan L, Sarkar A, Wang J, Wang W, Zhang Q, Broman KW, Korstanje R, Durrant C, Mott R, Iraqi FA, Pomp D, Threadgill D, Pardo-Manuel de Villena F, Churchill GA.
Genome Res. 2011 Aug;21(8):1223-38. PMCID: PMC3149489 [ Full Text ] [ Highlight in Nature Reviews Genetics ] [ datasets ]
Subspecific origin and haplotype diversity in the laboratory mouse
Yang H, Wang JR, Didion JP, Buus RJ, Bell TA, Welsh CE, Bonhomme F, Yu AH, Nachman MW, Pialek J, Tucker P, Boursot P, McMillan L, Churchill GA, de Villena FP.
Nat Genet. 2011 May 29;43(7):648-55. PMCID: PMC3125408 [ Full Text ] [ News Article ] [ datasets ]
Efficient genome ancestry inference in complex pedigrees with inbreeding
Liu EY, Zhang Q, McMillan L, de Villena FP, Wang W.
Bioinformatics. 2010 Jun 15;26(12):i199-207. PMCID: PMC2881372. [ Full Text ]
TreeQA: quantitative genome wide association mapping using local perfect phylogeny trees
Pan F, McMillan L, Pardo-Manuel De Villena F, Threadgill D, Wang W.
Pac Symp Biocomput. 2009:415-26. PMCID: PMC2739990. [ Full Text ]
The polymorphism architecture of mouse genetic resources elucidated using genome-wide resequencing data: implications for QTL discovery and systems genetics
Roberts A, Pardo-Manuel de Villena F, Wang W, McMillan L, Threadgill DW.
Mamm Genome. 2007 Jul;18(6-7):473-81. PMCID: PMC1998888 [ Full Text ]