Project description:In the decade following publication of the draft genome sequence of the domestic dog, extraordinary advances with application to several fields have been credited to the canine genetic system. Taking advantage of closed breeding populations and the subsequent selection for aesthetic and behavioral characteristics, researchers have leveraged the dog as an effective natural model for the study of complex traits, such as disease susceptibility, behavior and morphology, generating unique contributions to human health and biology. When designing genetic studies using purebred dogs, it is essential to consider the unique demography of each population, including estimation of effective population size and timing of population bottlenecks. The analytical design approach for genome-wide association studies (GWAS) and analysis of whole-genome sequence (WGS) experiments are inextricable from demographic data. We have performed a comprehensive study of genomic homozygosity, using high-depth WGS data for 90 individuals, and Illumina HD SNP data from 800 individuals representing 80 breeds. These data were coupled with extensive pedigree data analyses for 11 breeds that, together, allowed us to compute breed structure, demography, and molecular measures of genome diversity. Our comparative analyses characterize the extent, formation and implication of breed-specific diversity as it relates to population structure. These data demonstrate the relationship between breed-specific genome dynamics and population architecture, and provide important considerations influencing the technological and cohort design of association and other genomic studies.
Project description:Identificaiton of novel single-nucleotide polymorphism (SNP) candidates associated with chemo-responsiveness in colorectal cancers using microarray Response rates of 104 colorectal cancer patients to established regiments (FL, CAPE, FLOX, FLIRI) were evaluated by histoculture drug response assay. Affymetrix SNP 5.0 chips were used to determine genotypes of the same colorectal cancer patients. SNPs associated with chemosensitivity to standard regimens were identified by genome-wide association study. FL: 5-FU + Leucovorin; CA: Capecitabine, FLOX: 5-FU + Leucovorin + Oxaliplatin, FLIRI: 5-FU + Leucovorin + Irinotecan