Dr. Ostrander?s research interests are in the area of genetic mapping and genomics. We have two main areas of study. First, we are mapping and identifying genetic variants that increase susceptibility to breast and prostate cancer in humans. Both family and population-based studies are underway. Second, we are interested in the development of the canine system for both understanding the role of genetic variation in complex traits. ? ? Recently, we completed a genome wide scan of 255 prostate cancer families and identified several loci of interest. Stratification of our now complete dataset by clinical features of disease and family history, published this year, suggest multiple loci of interest that are currently the focus of extensive follow-up. In addition, we have completed testing of approximately 500 single nucleotide polymorphisms (SNPs) for association with prostate cancer risk and progression. Analysis of these data will highlight variants for additional and more detailed study. We have also participated in several meta analysis with the International Consortium of Prostate Cancer Genetics (ICPCG) to identify loci most likely to be relevant for susceptibility to aggressive forms of disease. As our recent joint publications illustrate, these results dovetail well with those reported by our own research group. ? ? With regard to breast cancer we have focused on understanding the role of the breast cancer susceptibility genes BRCA1 and BRCA2 in women drawn from the general population. Our most recent collaborative study has focused on a large data set of nearly 3000 women, 1/3 of whom are African American, to define profiles of women likely to be at increased risk for being a BRCA1 or BRCA2 carrier. We are also taking an evolutionary approach to understanding the role of missense changes in BRCA1/BRCA2, with a long term goal of identifying subtle variants of low genetic penetrance that are associated with increased disease risk. A subset of these data were summarized in a recent paper in Cancer Research. ? ? We and our collaborators have also developed resources that allows us to utilize the human, rodent and canine genome sequence for identifying variants important in disease susceptibility, behavior, and morphologic variation in the domestic dog. These data are embodied in the recent canine genome sequence report, published in Nature. We and colleagues are using those resources to identify loci for hip dysplasia, cancer (bladder, sarcoma, skin, lymphoma, and hemangiosarcoma), Addison?s disease, and osteoarthritis. In the past year, we reported loci for hip dysplasia, Addison's disease, and osteoarthritis. We have also seen the application these tools to issues related to conservation biology, and reported the first SNP analysis on wolves.? ? Additional canine studies focus on finding genes important in growth regulation by working closely with dog owners, breeders and kennel clubs. We are specifically interested in the organization of the canine phylogeny and the utility of linkage disequilibrium for mapping complex traits of interest. Towards that end we have identified both loci and sequence level variants that are under strong selection for regulating overall body size in the domestic dog and the evolutionary transition from wolf to dog. We and our collaborators reported this year on loci which regulate sexual dimorphism. Ongoing studies focus on identifying variants associated with leg length versus width, skull shape, and other morphologic features.
| Abadie, Jerome; Hedan, Benoit; Cadieu, Edouard et al. (2009) Epidemiology, pathology, and genetics of histiocytic sarcoma in the Bernese mountain dog breed. J Hered 100 Suppl 1:S19-27 |
| Derrien, Thomas; Theze, Julien; Vaysse, Amaury et al. (2009) Revisiting the missing protein-coding gene catalog of the domestic dog. BMC Genomics 10:62 |
| Udler, Miriam S; Azzato, Elizabeth M; Healey, Catherine S et al. (2009) Common germline polymorphisms in COMT, CYP19A1, ESR1, PGR, SULT1E1 and STS and survival after a diagnosis of breast cancer. Int J Cancer 125:2687-96 |
| Ostrander, Elaine A; Huson, Heather J; Ostrander, Gary K (2009) Genetics of athletic performance. Annu Rev Genomics Hum Genet 10:407-29 |
| Boyko, Adam R; Boyko, Ryan H; Boyko, Corin M et al. (2009) Complex population structure in African village dogs and its implications for inferring dog domestication history. Proc Natl Acad Sci U S A 106:13903-8 |
| Sutter, Nathan B; Bustamante, Carlos D; Chase, Kevin et al. (2007) A single IGF1 allele is a major determinant of small size in dogs. Science 316:112-5 |
| Cadieu, Edouard; Ostrander, Elaine A (2007) Canine genetics offers new mechanisms for the study of human cancer. Cancer Epidemiol Biomarkers Prev 16:2181-3 |
| Pierce, Brandon L; Friedrichsen-Karyadi, Danielle M; McIntosh, Laura et al. (2007) Genomic scan of 12 hereditary prostate cancer families having an occurrence of pancreas cancer. Prostate 67:410-5 |
| Quignon, Pascale; Herbin, Laetitia; Cadieu, Edouard et al. (2007) Canine population structure: assessment and impact of intra-breed stratification on SNP-based association studies. PLoS ONE 2:e1324 |
| Wayne, Robert K; Ostrander, Elaine A (2007) Lessons learned from the dog genome. Trends Genet 23:557-67 |
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