HomeResearchIntramural ResearchResearch Branches at NHGRICancer Genetics Branch Ostrander Lab

Elaine A. Ostrander, Ph.D. Chief & Senior Investigator Cancer Genetics Branch Head Comparative Genetics Section B.S. University of Washington, 1981 Ph.D. Oregon Health Sciences University, 1987 (301) 594-5284 (301) 594-0023 eostrand@mail.nih.gov Building 50, Room 5351 50 South Dr, MSC 8000 Bethesda, MD 20892-8000 Selected Publications The NHGRI Dog Genome Project

Dr. Ostrander's laboratory maps genes responsible for cancer susceptibility in canines and humans. Cancer is the number one killer of dogs, and studying the major cancers in dogs provides a remarkably valuable approach for developing a better-understanding of the development of cancer in humans. The clinical presentation, histology, and biology of many canine cancers very closely parallel those of human malignancies, so comparative studies of canine and human cancer genetics should be of significant clinical benefit to both.

Naturally occurring pedigrees of dogs are large, multigenerational, and the result of directed matings, all of which favor the expression of recessive disorders, such as cancers. Using information from these pedigrees, Dr. Ostrander's laboratory is constructing and using high-density maps of the canine genome to identify genes that increase susceptibility to genetic forms of lymphoma, osteosarcoma, and kidney cancer. Her group also has undertaken a large single-nucleotide polymorphism (SNP) study to determine the inter-relatedness of dog breeds. This study demonstrated that differences among breeds account for about 30 percent of genetic variation within dogs. In addition, it demonstrated that genotyping could be used to assign 99 percent of individual dogs to their correct breeds. Phylogenetic analysis also allows several breeds with ancient origins to be separated from the remaining breeds with modern European origins. This work sets the stage for Dr. Ostrander and her collaborators to begin the cloning of genes identified in linkage studies by identifying ancestral chromosomes that contribute the same genetic mutation to a multitude of dog breeds.

Dr. Ostrander's laboratory also is interested in prostate and breast cancer susceptibility genes in humans. With their collaborators, they have undertaken a genome-wide scan for prostate cancer susceptibility genes in a cohort of 254 high-risk families. Their data thus far demonstrate that prostate cancer is genetically very heterogeneous and that multiple loci are likely to be important. Loci on chromosomes 1, 6, 8, and 17 are the focus of current studies. In a population-based, case-control study of middle-aged men and prostate cancer, Dr. Ostrander's group investigated the role of several candidate SNPs and found that genes in the androgen receptor and P450 pathways are critical to prostate susceptibility and long-term outcomes.

Finally, Dr. Ostrander's laboratory is interested in the frequency and distribution of mutations in known cancer susceptibility genes in the general population (that is, other than in high-risk families). They recently completed two screening studies looking for BRCA1 and BRCA2 mutations in women from the general population with breast cancer. The first study, an analysis of 1,600 women, was performed as part of the Shanghai Breast Self Examination (BSE) Trial, involving 267,000 women in Shanghai, China. The second study is an ancillary project studying data from 2,300 Caucasian and African-American women between the ages of 35 and 64, built on the foundation of the large NICHD Women's CARE Study. Dr. Ostrander's group currently is analyzing the data to identify both protein-truncating and missense changes that are likely to be associated with disease. To accomplish the latter, they are using comparative genomics - cloning and sequencing the BRCA1 and BRCA2 genes from lower mammals and identifying regions that are either highly conserved or evolving under positive selection - to identify missense changes in those regions. Such changes are likely to represent weakly penetrant disease alleles and will be the focus of new functional studies.

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Last Reviewed: August 12, 2008