Elaine A. Ostrander, Ph.D.

Chief & NIH Distinguished Investigator

Cancer Genetics and Comparative Genomics Branch

Education

B.S. University of Washington, 1981

Ph.D. Oregon Health Sciences University, 1987

Contact Info

BG 50 RM 5351
50 SOUTH DR 8000
BETHESDA MD 20892

Biography

Dr. Elaine Ostrander is Chief and Distinguished Senior Investigator of the Cancer Genetics and Comparative Genomics Branch at the National Human Genome Research Institute of NIH. She also heads the Section of Comparative Genetics. She received her Ph.D. from the Oregon Health and Science University and did her initial postdoctoral training at Harvard and UC Berkeley. She then went to the Lawrence Berkeley National Labs where, with collaborators, she began the canine genome project, assembling the foundational resources needed to navigate the canine genome. Dr. Ostrander joined the faculty of the Fred Hutchinson Cancer Research Center and University of Washington in 1993, rising to the rank of Member in the Human Biology and Clinical Research Divisions, and head of the Genetics Program. She moved to NIH in 2004 to assume a position of Chief and Senior Investigator at NHGRI.

Dr. Ostrander's lab at has traditionally worked in the fields of both human and canine genetics. Her lab uses state-of-the-art genomic approaches to identify prostate cancer susceptibility genes in both high-risk families and population-base, case control studies. She has identified alleles that increase risk for metastatic disease and continues to work within two large consortia to identify susceptibility loci. Hers was one of the first labs to describe a role for BRCA1 and BRCA2 mutations in women drawn from the general population, revealing epidemiologic features of woman at risk for breast or ovarian cancer.

Dr. Ostrander’s lab is best known, though, for their studies of the domestic dog as a well-phenotyped species with an extensively documented population structure that offers unique opportunities for solving fundamental biological problems. Human selection has differentiated the dog into a staggering variety of breeds, each featuring a narrow, precisely defined set of phenotypes. Recognizing that this combination of diversity and uniformity provides an exceptional opportunity for genetic dissection of biological processes, her lab has applied these advantages to tackling problems in cell and organismal biology, and human disease, which have proven intractable in other model systems.

The Ostrander lab assembled the first catalogues of canine genomic variation, constructed the first linkage map, and was first to describe megabase linkage disequilibrium in dogs, showing how large loci, such as those for squamous cell carcinoma, could be reduced to single variants by taking advantage of breed relatedness. The lab continues to refine our knowledge of breeds by building a phylogeny of breeds that spans the world, and through leadership in the International Dog10K Sequencing Consortium. The lab has further exploited canine genome organization to study disease susceptibility, working with collaborators to identify genes for Addison’s disease, retinopathies, and cancer, all of which have contributed to our understanding of comparable human diseases, as well as traits like athleticism.

In recent years, lab studies have revealed how modifications in small numbers of genes produce the enormous differences in canine body shape and size that characterize the spectrum of breeds. While the lab has identified genes, and often variants, controlling head shape, ear shape, leg length, fur length, etc., it is the work on breed body size that has revealed some of the most compelling and surprising features of canine biology. Less than 25 genes control most of the variance between large and small breeds and most morphologic features in breeds are controlled by small numbers of genes of large effect, rather than the opposite, as is typical in humans.

Dr. Ostrander has published over 375 papers. She has won multiple awards including the American Cancer Society Junior Faculty Award, Burroughs Welcome Award for Functional Genomics, Asa Mays Award, Lifetime Achievement Awards and the 2013 Genetics Society of America Medal. She has also won multiple mentorship awards, was elected a fellow of AAAS in 2013, and was elected to the National Academy of Science in 2019.

Biography

Dr. Elaine Ostrander is Chief and Distinguished Senior Investigator of the Cancer Genetics and Comparative Genomics Branch at the National Human Genome Research Institute of NIH. She also heads the Section of Comparative Genetics. She received her Ph.D. from the Oregon Health and Science University and did her initial postdoctoral training at Harvard and UC Berkeley. She then went to the Lawrence Berkeley National Labs where, with collaborators, she began the canine genome project, assembling the foundational resources needed to navigate the canine genome. Dr. Ostrander joined the faculty of the Fred Hutchinson Cancer Research Center and University of Washington in 1993, rising to the rank of Member in the Human Biology and Clinical Research Divisions, and head of the Genetics Program. She moved to NIH in 2004 to assume a position of Chief and Senior Investigator at NHGRI.

Dr. Ostrander's lab at has traditionally worked in the fields of both human and canine genetics. Her lab uses state-of-the-art genomic approaches to identify prostate cancer susceptibility genes in both high-risk families and population-base, case control studies. She has identified alleles that increase risk for metastatic disease and continues to work within two large consortia to identify susceptibility loci. Hers was one of the first labs to describe a role for BRCA1 and BRCA2 mutations in women drawn from the general population, revealing epidemiologic features of woman at risk for breast or ovarian cancer.

Dr. Ostrander’s lab is best known, though, for their studies of the domestic dog as a well-phenotyped species with an extensively documented population structure that offers unique opportunities for solving fundamental biological problems. Human selection has differentiated the dog into a staggering variety of breeds, each featuring a narrow, precisely defined set of phenotypes. Recognizing that this combination of diversity and uniformity provides an exceptional opportunity for genetic dissection of biological processes, her lab has applied these advantages to tackling problems in cell and organismal biology, and human disease, which have proven intractable in other model systems.

The Ostrander lab assembled the first catalogues of canine genomic variation, constructed the first linkage map, and was first to describe megabase linkage disequilibrium in dogs, showing how large loci, such as those for squamous cell carcinoma, could be reduced to single variants by taking advantage of breed relatedness. The lab continues to refine our knowledge of breeds by building a phylogeny of breeds that spans the world, and through leadership in the International Dog10K Sequencing Consortium. The lab has further exploited canine genome organization to study disease susceptibility, working with collaborators to identify genes for Addison’s disease, retinopathies, and cancer, all of which have contributed to our understanding of comparable human diseases, as well as traits like athleticism.

In recent years, lab studies have revealed how modifications in small numbers of genes produce the enormous differences in canine body shape and size that characterize the spectrum of breeds. While the lab has identified genes, and often variants, controlling head shape, ear shape, leg length, fur length, etc., it is the work on breed body size that has revealed some of the most compelling and surprising features of canine biology. Less than 25 genes control most of the variance between large and small breeds and most morphologic features in breeds are controlled by small numbers of genes of large effect, rather than the opposite, as is typical in humans.

Dr. Ostrander has published over 375 papers. She has won multiple awards including the American Cancer Society Junior Faculty Award, Burroughs Welcome Award for Functional Genomics, Asa Mays Award, Lifetime Achievement Awards and the 2013 Genetics Society of America Medal. She has also won multiple mentorship awards, was elected a fellow of AAAS in 2013, and was elected to the National Academy of Science in 2019.

Scientific Summary

The Ostrander lab is focused on three primary regions of canine genetic research: drivers of behavioral and morphological variation, breed structure and development, and risk factors for breed-specific canine cancers. As such, the researchers are building on the extensive genomic infrastructure we developed for the dog to identify genetic and genomic inheritance patterns relevant to our aims. Domestic dogs present an intriguing model for genetic research, as breed predilection likely reflects the selective pressures used to develop and enhance specific traits. Knowledge obtained from their research efforts extends beyond dogs to human development and disease, with a specific lab focus on prostate cancer (PC), where they are working both independently and within consortia to find genes associated with susceptibility and progression to aggressive forms of PC.

Canine Morphology: The Ostrander lab has long championed ¹ the canine system for the study of complex traits by building maps ^2,3 , organizing sequencing ⁴ of the canine genome, and studying population structure ⁵, domestication ⁶ , and performance ^7,8. In doing so they have demonstrated the power of breed structure for mapping traits that are have proven intractable through human studies ⁹ . The lab's ability to map the genetic underpinnings of body size ^10,11, pelage ^12,13,14, leg length ¹⁵, skull shape ^16,17, and other phenotypes has provided unique insights into the fundamental biology of natural phenotypic variation in mammals, offering a completely new lens for viewing these processes in humans. They have built large data sets for such studies, including genome-wide marker coverage of 161 breeds and over 1300 dogs, whole-genome sequencing of 722 distinct canids including pure and mixed breeds, village dogs, and wild canids, and prominent participation in the Dog10K project ³⁰. The lab's near term aims focus on elucidation of further body size variants and mapping and functional studies of breed-specific behavioral characteristics.

Breed Structure: Many of the canine projects in the Ostrander lab rely on the traditional organization of domestic dogs into breeds, defined by their histories of specific selection toward ideal physical and behavioral traits. Understanding the genetic relationships between breeds ⁵ and the impact that selection has on the genomes of closed populations ¹⁸further informs future study design. Knowledge of these breed relationships and routes of breed formation further facilitate strategies for categorization of landrace breeds ¹⁹, confirmation of re-discovery of rare wild populations ²⁰ , impact of modern designer breed formation ²¹, and connection to historic human-canine bonds ²² .

Canine Cancer:

Cancer mapping studies in humans often fail due to sample size limitations and locus heterogeneity; factors the Ostrander lab argues can often be overcome in canines ²³. Dogs generally develop cancer in the same organs and respond to similar therapies as humans. However, predisposition to cancer type is often breed-specific. The lab first demonstrated the utility of dogs for cancer genetics by mapping kidney cystadeno-carcinoma in German Shepherds, prior to its localization in humans ²⁴.

The group subsequently tackled other cancers, including: histiocytic sarcoma ²⁵, somatic cell carcinoma of the digit ²⁶, transitional cell carcinoma of the bladder ^27,28, and canine transmissible venereal tumors ²⁹.

Prostate Cancer:

We have worked for the last 25 years with long-time collaborators at the Fred Hutchinson Cancer Research Center (FHCRC). Our collaborative group was the first to show that variation in the androgen receptor is associated with disease risk in men with high body mass index ³¹ . We helped ascertainment 307 “high risk” hereditary prostate cancer families and published genome-wide linkage scans of ever-higher resolution ^32,33,34, identifying putative susceptibility loci ^35,36,37. Our group used association studies to identify risk loci and demonstrated an association between prostate cancer risk with several genic SNPs, e.g., VDR, CYP17, megalin, CHEK2, JAK2, STAT3, etc. and recurrence ^{38,39,40,41,42}. Our collaborative studies of epigenetic profiling identified novel prognostic biomarkers of metastatic lethal progression. In studies led by the FHCRC, Prostate Cancer-Specific Mortality-associated SNPs were identified, which are predictive for patients with an increased risk for fatal prostate cancer ^43,44. Finally, our group was the first to describe the somatic mutational landscape of BRCA2-associated aggressive prostate tumors, defining a signature of an increased somatic mutation rate, depletion of context-specific C>T substitutions, and an enrichment for deletions ⁴⁵. Most recent collaborations identified new prostate cancer-associated metastatic lethal variants and included gene expression studies ^{46,47,48,49,50,51}.

Scientific Summary

The Ostrander lab is focused on three primary regions of canine genetic research: drivers of behavioral and morphological variation, breed structure and development, and risk factors for breed-specific canine cancers. As such, the researchers are building on the extensive genomic infrastructure we developed for the dog to identify genetic and genomic inheritance patterns relevant to our aims. Domestic dogs present an intriguing model for genetic research, as breed predilection likely reflects the selective pressures used to develop and enhance specific traits. Knowledge obtained from their research efforts extends beyond dogs to human development and disease, with a specific lab focus on prostate cancer (PC), where they are working both independently and within consortia to find genes associated with susceptibility and progression to aggressive forms of PC.

Canine Morphology: The Ostrander lab has long championed ¹ the canine system for the study of complex traits by building maps ^2,3 , organizing sequencing ⁴ of the canine genome, and studying population structure ⁵, domestication ⁶ , and performance ^7,8. In doing so they have demonstrated the power of breed structure for mapping traits that are have proven intractable through human studies ⁹ . The lab's ability to map the genetic underpinnings of body size ^10,11, pelage ^12,13,14, leg length ¹⁵, skull shape ^16,17, and other phenotypes has provided unique insights into the fundamental biology of natural phenotypic variation in mammals, offering a completely new lens for viewing these processes in humans. They have built large data sets for such studies, including genome-wide marker coverage of 161 breeds and over 1300 dogs, whole-genome sequencing of 722 distinct canids including pure and mixed breeds, village dogs, and wild canids, and prominent participation in the Dog10K project ³⁰. The lab's near term aims focus on elucidation of further body size variants and mapping and functional studies of breed-specific behavioral characteristics.

Breed Structure: Many of the canine projects in the Ostrander lab rely on the traditional organization of domestic dogs into breeds, defined by their histories of specific selection toward ideal physical and behavioral traits. Understanding the genetic relationships between breeds ⁵ and the impact that selection has on the genomes of closed populations ¹⁸further informs future study design. Knowledge of these breed relationships and routes of breed formation further facilitate strategies for categorization of landrace breeds ¹⁹, confirmation of re-discovery of rare wild populations ²⁰ , impact of modern designer breed formation ²¹, and connection to historic human-canine bonds ²² .

Canine Cancer:

Cancer mapping studies in humans often fail due to sample size limitations and locus heterogeneity; factors the Ostrander lab argues can often be overcome in canines ²³. Dogs generally develop cancer in the same organs and respond to similar therapies as humans. However, predisposition to cancer type is often breed-specific. The lab first demonstrated the utility of dogs for cancer genetics by mapping kidney cystadeno-carcinoma in German Shepherds, prior to its localization in humans ²⁴.

The group subsequently tackled other cancers, including: histiocytic sarcoma ²⁵, somatic cell carcinoma of the digit ²⁶, transitional cell carcinoma of the bladder ^27,28, and canine transmissible venereal tumors ²⁹.

Prostate Cancer:

We have worked for the last 25 years with long-time collaborators at the Fred Hutchinson Cancer Research Center (FHCRC). Our collaborative group was the first to show that variation in the androgen receptor is associated with disease risk in men with high body mass index ³¹ . We helped ascertainment 307 “high risk” hereditary prostate cancer families and published genome-wide linkage scans of ever-higher resolution ^32,33,34, identifying putative susceptibility loci ^35,36,37. Our group used association studies to identify risk loci and demonstrated an association between prostate cancer risk with several genic SNPs, e.g., VDR, CYP17, megalin, CHEK2, JAK2, STAT3, etc. and recurrence ^{38,39,40,41,42}. Our collaborative studies of epigenetic profiling identified novel prognostic biomarkers of metastatic lethal progression. In studies led by the FHCRC, Prostate Cancer-Specific Mortality-associated SNPs were identified, which are predictive for patients with an increased risk for fatal prostate cancer ^43,44. Finally, our group was the first to describe the somatic mutational landscape of BRCA2-associated aggressive prostate tumors, defining a signature of an increased somatic mutation rate, depletion of context-specific C>T substitutions, and an enrichment for deletions ⁴⁵. Most recent collaborations identified new prostate cancer-associated metastatic lethal variants and included gene expression studies ^{46,47,48,49,50,51}.

PCA Genetic Consortium

We have, and continue to be, part of two major consortia:

The International Consortium for Prostate Cancer Genetics (ICPCG)
(Dr. Ostrander was one of several founding members.)
The PRACTICAL Consortium
(Led by Dr. Ros Eeles from Cambridge.)

Referencing only work prior to 2017, ICPCG uses a family-based approach to identify or validate putative risk loci. PRACTICAL uses GWAS involving several thousand individuals with cohort data contributed by individual research groups to identify large numbers of variants of small effect, as summarized in several papers. We have been part of recent high-profile papers, most aimed at identifying new susceptibility loci, with a special focus on men of African ancestry.

PCA Genetic Consortium
We have, and continue to be, part of two major consortia:

The International Consortium for Prostate Cancer Genetics (ICPCG)
(Dr. Ostrander was one of several founding members.)

The PRACTICAL Consortium
(Led by Dr. Ros Eeles from Cambridge.)

Referencing only work prior to 2017, ICPCG uses a family-based approach to identify or validate putative risk loci. PRACTICAL uses GWAS involving several thousand individuals with cohort data contributed by individual research groups to identify large numbers of variants of small effect, as summarized in several papers. We have been part of recent high-profile papers, most aimed at identifying new susceptibility loci, with a special focus on men of African ancestry.

Publications

Serres-Armero A, Davis BW, Povolotskaya IS, Morcillo-Surarez C, Plassais J, Juan D, Ostrander EA, Marques-Bonet T. Copy number variation underlies complex phenotypes in domestic dog breeds and other canids. Genome Res. 2020. (In Press)

Surbakti S, Parker HG, McIntyre JK, Maury HK, Cairns KM, Selvig M, Pangau-Adam M, Safonpo A, Numberi L, Runtuboi DYP, Davis BW, Ostrander EA. New Guinea highland wild dogs are the original New Guinea Singing dogs. Proc Natl Acad Sci U S A. Sep 29;117(39):24369-24376. doi:10.1073/pnas.2007242117. 2020. [PubMed]

Wang T, Ma J, Hogan AN, Fong S, Licon K, Tsui B, Kreisberg JF, Adams PD, Carvunis AR, Bannasch DL, Ostrander EA, Ideker T. Quantitative translation of dog-to-human aging by conserved remodeling of the DNA methylome. Cell Syst. Aug 26;11(2):176-185.e6. doi:10.1016/j.cels.2020.06.006. 2020. [PubMed]

Parker HG, Dhawan D, Harris AC, Ramos-Vara JA, Davis BW, Knapp DW, Ostrander EA. RNAseq expression patterns of canine invasive urothelial carcinoma reveal two distinct tumor clusters and shared regions of dysregulation with human bladder tumors. BMC Cancer. Mar 24;20(1):251. doi:10.1186/s12885-020-06737-0. 2020. [PubMed]

Ostrander EA, Wang G-D, Larson G, vonHoldt BM, Davis BW, Jagannathan V, Hitte C, Wayne RK, Zhang, Y-P, Dog10K Consortium. Dog10K: an international sequencing effort to advance studies of canine domestication, phenotypes, and health. Natl Sci Rev. Jul;6(4):810-824. doi:10.1093/nsr/nwz049. 2019. [PubMed]

Plassais J, Kim J, Davis BW, Karyadi DM, Hogan AN, Harris AC, Decker B, Parker HG, Ostrander EA. Whole genome sequencing of canids reveals genomic regions under selection and variants influencing morphology. Nat Comm. Apr 2;10(1):1489. doi:10.1038/s41467-019-09373-w. 2019. [PubMed]

Kim J, Williams FJ, Dreger DL, Plassais J, Davis BW, Parker HG, Ostrander EA. Genetic selection of athletic success in sport hunting dogs. Proc Natl Acad Sci U S A. Jul 24;115(30):E7212-E7221. doi:10.1073/pnas.1800455115. 2018. [PubMed]

Ostrander EA, Wayne RK, Freedman AH, Davis BW. Evolutionary genetics of the dog. Nature Rev Genet. Dec;18(12):705-720. doi:10.1038/nrg.2017.67. 2017. [PubMed]

vonHoldt BM, Shuldiner E, Janowitz-Koch I, Kartzinel RY, Hogan A, Brubaker L, Wanser S, Stahler D, Wynne CDL, Ostrander EA, Sinsheimer JS, Udell MAR. Structural variants in genes associated with human Williams-Beuren syndrome underlie stereotypical hypersociability in domestic dogs. SciAdvances. Jul 19;3(7):e1700398. doi:10.1126/sciadv.1700398. 2017. [PubMed]

Parker HG, Dreger DL, Rimbault M, Davis BW, Mullen AM, Carpintero-Ramirez G, Ostrander EA.. Genomic analysis reveals the influence of geographic origin, immigration and cross-breed introgression on modern dog breed development. CellReports. Apr 25;19(4):697-708. doi:10.1016/j.celrep.2017.03.079. 2017. [PubMed]

Plassais J, Rimbault M, Williams FJ, Davis BW, Schoenebeck JJ, Ostrander EA. Analysis of large versus small dogs reveals three genes on the canine X chromosome associated with body weight, muscling and back fat thickness. PLoS Genet. Mar 3;13(3):e1006661. doi:10.1371/journal.pgen.1006661. 2017. [PubMed]

Parker HG, Harris A, Dreger DL, Ostrander EA. The bald and the beautiful: hairlessness in domestic dog breeds. PhilosophTransactRSocLondBBiolSci. Feb 5;372(1713):20150488. doi:10.1098/rstb.2015.0488. 2017. [PubMed]

Dreger DL, Rimbault M, Davis BW, Bhatnager A, Parker HG, Ostrander EA. Whole-genome sequence, SNP chips and pedigree structure: building demographic profiles in domestic dog breeds to optimize genetic-trait mapping. Dis Mod Mech. Dec 1;9(12):1445-1460. doi:10.1242/dmm.027037. 2016. [PubMed]

Decker B, Karyadi DM, Davis BW, Karlins E, Tillmans LS, Stanford JL, Thibodeau SN, Ostrander EA. Biallelic BRCA mutations shape the somatic mutational landscape of aggressive prostate tumors. Am J Hum Genet. May 5;98(5):818-829. doi:10.1016/j.ajhg.2016.03.003. 2016. [PubMed]

Decker B, Davis BW, Rimbault M, Long AH, Karlins E, Jagannathan V, Reiman R, Parker HG, Drögemüller C, Corneveaux JJ, Chapman ES, Trent JM, Leeb T, Huentelman JM, Wayne RK, Karyadi DM, Ostrander EA. Comparison against 186 canid whole-genome sequences reveals survival strategies of an ancient clonally transmissible canine tumor. GenomeRes. Nov;25(11):1646-55. doi:10.1101/gr,190314.115. 2015. [PubMed]

Decker B, Parker HG, Dhawan D, Kwon EM, Karlins E, Davis BW, Ramos-Vara JA, Bonney PL, McNiel EA, Knapp DW, Ostrander EA. Homologous mutation to human BRAF V600E is common in naturally occurring canine bladder cancer-evidence for a relevant model system and urine-based diagnostic test. Mol Canc Res. Jun;13(6):993-1002. doi:10.1158/1541-7786.MCR-14-0689. 2015. [PubMed]

Parker HG, Ostrander EA. Cancer. Hiding in plain view-an ancient dog in the modern world. Science. Jan 24;343(6169):376-8. doi:10.1126/science.1248812. 2014. [PubMed]

Rimbault M, Beale HC, Schoenebeck JJ, Hoopes BC, Allen JJ, Kilroy-Glynn P, Wayne RK, Sutter NB, Ostrander EA. Derived variants at six genes explain nearly half of size reduction in dog breeds. Genome Res. Dec;23(12):1985-95. doi:10.1101/gr.157339.113. 2013. [PubMed]

Karyadi DM, Karlins E, Decker B, vonHoldt BM, Carpintero-Ramirez G, Parker HG, Wayne RK, Ostrander EA. A copy number variant at the KITLG locus likely confers risk for canine squamous cell carcinoma of the digit. PLoSGenetics. Mar;9(3):e1003409. doi:10.1371/journal.pgen.1003409. 2013. [PubMed]

Schoenebeck JJ, Hutchinson SA, Byers A, Beale HC, Carrington B, Faden DL, Rimbault M, Decker B, Kidd JM, Sood R, Boyko AR, Fondon JW 3rd, Wayne RK, Bustamante CD, Ciruna B, Ostrander EA. Variation of BMP3 contributes to dog breed skull diversity. PLoSGenet. 8(8):e1002849. doi:10.1371/journal.pgen.1002849. 2012. [PubMed]

Huson HJ, vonHoldt BM, Rimbault M, Byers AM, Runstadler JA, Parker HG, Ostrander EA. Breed-specific ancestry studies and genome-wide association analysis highlight an association between the MYH9 gene and heat tolerance in Alaskan sprint racing sled dogs. MammGenome. Feb;23(1-2):178-94. doi:10.1007/s00335-011-9374-y. 2012. [PubMed]

Boyko AR, Quignon P, Li L, Schoenebeck JJ, Degenhardt JD, Lohmueller KE, Zhao K, Brisbin A, Parker HG, vonHoldt BM, Cargill M, Auton A, Reynolds A, Elkahloun AG, Castelhano M, Mosher DS, Sutter NB, Johnson GS, Novembre J, Hubisz MJ, Siepel A, Wayne RK, Bustamante CD, Ostrander EA. A simple genetic architecture underlies morphologic variation in dogs. PLoS Biol. Aug 10;8(8):e1000451. doi:10.1371/journal.pgen.1000451. 2010. [PubMed]

vonHoldt BM, Pollinger JP, Lohmueller KE, Han E, Parker HG, Quignon P, Degenhardt JD, Boyko AR, Earl DA, Auton A, Reynolds A, Bryc K, Brisbin A, Knowles JC, Mosher DS, Spady TC, Elkahloun A, Geffen E, Pilot M, Jedrzejewski W, Greco C, Randi E, Bannasch D, Wilton A, Shearman J, Musiani M, Cargill M, Jones PG, Qian Z, Huang W, Ding ZL, Zhang YP, Bustamante CD, Ostrander EA, Novembre J, Wayne RK. Genome-wide SNP and haplotype analyses reveal a rich history underlying dog domestication. Nature. Apr 8;464(7290):898-902. doi:10.1038/nature08837. 2010. [PubMed]

Cadieu E, Neff MW, Quignon P, Walsh K, Chase K, Parker HG, vonHoldt BM, Rhue A, Boyko A, Byers A, Wong A, Mosher DS, Elkahloun AG, Spady TC, André C, Lark KG, Cargill M, Bustamante CD, Wayne RK, Ostrander EA. Coat variation in the domestic dog is governed by variants in three genes. Science. Oct 2;326(5949):150-3. doi:10.1126/science.1177808. 2009. [PubMed]

Parker HG, vonHoldt BM, Quignon P, Margulies EH, Shao S, Mosher DS, Spady TC, Elkahloun A, Cargill M, Jones PG, Maslen CL, Acland GM, Sutter NB, Kuroki K, Bustamante CD, Wayne RK, Ostrander EA. An expressed Fgf4 retrogene is associated with breed-defining chondrodysplasia in domestic dogs. Science. Aug 21;325(5943):995-8. doi:10.1126/science.1173275. 2009. [PubMed]

Parker HG, Kukekova AV, Akey DT, Goldstein O, Kirkness EF, Baysac KC, Mosher DS, Aguirre GD, Acland GM, Ostrander EA. Breed relationships facilitate fine mapping studies: A 7.8 Kb deletion cosegregates with collie eye anomaly across multiple dog breeds. Genome Res. Nov;17(11):1562-71. doi:10.1101/gr.6772807. 2007. [PubMed]

Mosher DS, Quignon P, Bustamante CD, Sutter NB, Mellersh CS, Parker HG, Ostrander EA. A mutation in the myostatin gene increases muscle mass and enhances racing performance in heterozygote dogs. PLoS Genet. May 25;3(5):e79. doi:10.1371/journal.pgen.0030079. 2007. [PubMed]

Sutter NB, Bustamante CD, Chase K, Gray MM, Zhao K, Zhu L, Padhukasahasram B, Karlins E, Davis S, Jones PG, Quignon P, Johnson GS, Parker HG, Fretwell N, Mosher DS, Lawler DF, Satyaraj E, Nordborg M, Lark KG, Wayne RK, Ostrander EA. A single IGF1 Allele is a major determinant of small size in dogs. Science. Apr 6;316(5821):112-5. doi:10.1126/science.1137045. 2007. [PubMed]

Agalliu I, Kwon EM, Zadory D, McIntosh L, Thompson J, Stanford JL, Ostrander EA. Germline mutations in the BRCA2 gene and susceptibility to hereditary prostate cancer. Clin Cancer Res. Feb 1;13(3):839-43. doi:10.1158/1078-0432.CCR-06-2164. 2007. [PubMed]

Parker HG, Kruglyak L, Ostrander EA. Molecular genetics: DNA analysis of a putative dog clone. Nature. Mar 9;440(7081):E1-2. doi:10.1038/nature04685. 2006. [PubMed]

Sutter NB, Eberle MA, Parker HG, Pullar BJ, Kirkness EF, Kruglyak L, Ostrander EA. Extensive and breed specific linkage disequilibrium in Canis familiaris. Genome Res. Dec;14(12):2388-96. doi:10.1101/gr.3147604. 2004. [PubMed]

Parker HG, Kim LV, Sutter NB, Carlson S, Lorentzen TD, Malek TB, Johnson GS, DeFrance HB, Ostrander EA, Kruglyak L. Genetic structure of the purebred domestic dog. Science. May 21;304(5674):1160-4. doi:10.1126/science.1097406. 2004. [PubMed]

Lingaas F, Comstock KE, Kirkness EF, Sørensen A, Aarskaug T, Hitte C, Nickerson ML, Moe L, Schmidt LS, Thomas R, Breen M, Galibert F, Zbar B, Ostrander EA. A mutation in the canine BHD gene is associated with hereditary multifocal renal cystadenocarcinoma and nodular dermatofibrosis in the German Shepherd Dog. Hum Mol Genet. Dec 1;12(23):3043-53. doi:10.1093/hmg/ddg336. 2003. [PubMed]

Guyon R, Lorentzen TD, Hitte C, Kim L, Cadieu E, Parker HG, Quignon P, Lowe JK, Renier C, Gelfenbeyn B, Vignaux F, DeFrance HB, Gloux S, Mahairas GG, André C, Galibert F, Ostrander EA. A 1-Mb resolution radiation hybrid map of the canine genome. Proc Natl Acad Sci U S A. Apr 29;100(9):5296-301. doi:10.1073/pnas.0831002100. 2003. [PubMed]

Fleming MA, Potter JD, Ramirez CJ, Ostrander GK, Ostrander EA. Understanding missense mutations in the BRCA1 gene: an evolutionary approach. Proc Natl Acad Sci U S A. Feb 4;100(3):1151-6. doi:10.1073/pnas.0237285100. 2003. [PubMed]

Jónasdóttir TJ, Mellersh CS, Moe L, Heggebø R, Gamlem H, Ostrander EA, Lingaas F. Genetic mapping of a naturally occurring hereditary renal cancer syndrome in dogs. Proc Natl Acad Sci U S A. Apr 11;97(8):4132-7. doi:10.1073/pnas.070053397. 2000. [PubMed]

Malone KE, Daling JR, Thompson JD, O'Brien CA, Francisco LV, Ostrander EA. BRCA1 mutations and breast cancer in the general population: Analyses in women before age 35 years and in women before age 45 years with first-degree family history. J Am Med Assoc. Mar 25;279(12):922-9. doi:10.1001/jama.279.12.922. 1998. [PubMed]

Mellersh CS, Langston AA, Acland GM, Fleming MA, Ray K, Wiegand NA, Francisco LV, Gibbs M, Aguirre GD, Ostrander EA. A linkage map of the canine genome. Genomics. Dec 15;46(3):326-36. doi:10.1006/geno.1997.5098. 1997. [PubMed]

Langston AA, Malone KE, Thompson JD, Daling JR, Ostrander EA. BRCA1 mutations in a population-based sample of young women with breast cancer. N Engl J Med. Jan 18;334(3):137-42. doi:10.1056/NEJM199601183340301. 1996. [PubMed]

Publications

Serres-Armero A, Davis BW, Povolotskaya IS, Morcillo-Surarez C, Plassais J, Juan D, Ostrander EA, Marques-Bonet T. Copy number variation underlies complex phenotypes in domestic dog breeds and other canids. Genome Res. 2020. (In Press)

Surbakti S, Parker HG, McIntyre JK, Maury HK, Cairns KM, Selvig M, Pangau-Adam M, Safonpo A, Numberi L, Runtuboi DYP, Davis BW, Ostrander EA. New Guinea highland wild dogs are the original New Guinea Singing dogs. Proc Natl Acad Sci U S A. Sep 29;117(39):24369-24376. doi:10.1073/pnas.2007242117. 2020. [PubMed]

Wang T, Ma J, Hogan AN, Fong S, Licon K, Tsui B, Kreisberg JF, Adams PD, Carvunis AR, Bannasch DL, Ostrander EA, Ideker T. Quantitative translation of dog-to-human aging by conserved remodeling of the DNA methylome. Cell Syst. Aug 26;11(2):176-185.e6. doi:10.1016/j.cels.2020.06.006. 2020. [PubMed]

Parker HG, Dhawan D, Harris AC, Ramos-Vara JA, Davis BW, Knapp DW, Ostrander EA. RNAseq expression patterns of canine invasive urothelial carcinoma reveal two distinct tumor clusters and shared regions of dysregulation with human bladder tumors. BMC Cancer. Mar 24;20(1):251. doi:10.1186/s12885-020-06737-0. 2020. [PubMed]

Ostrander EA, Wang G-D, Larson G, vonHoldt BM, Davis BW, Jagannathan V, Hitte C, Wayne RK, Zhang, Y-P, Dog10K Consortium. Dog10K: an international sequencing effort to advance studies of canine domestication, phenotypes, and health. Natl Sci Rev. Jul;6(4):810-824. doi:10.1093/nsr/nwz049. 2019. [PubMed]

Plassais J, Kim J, Davis BW, Karyadi DM, Hogan AN, Harris AC, Decker B, Parker HG, Ostrander EA. Whole genome sequencing of canids reveals genomic regions under selection and variants influencing morphology. Nat Comm. Apr 2;10(1):1489. doi:10.1038/s41467-019-09373-w. 2019. [PubMed]

Kim J, Williams FJ, Dreger DL, Plassais J, Davis BW, Parker HG, Ostrander EA. Genetic selection of athletic success in sport hunting dogs. Proc Natl Acad Sci U S A. Jul 24;115(30):E7212-E7221. doi:10.1073/pnas.1800455115. 2018. [PubMed]

Ostrander EA, Wayne RK, Freedman AH, Davis BW. Evolutionary genetics of the dog. Nature Rev Genet. Dec;18(12):705-720. doi:10.1038/nrg.2017.67. 2017. [PubMed]

vonHoldt BM, Shuldiner E, Janowitz-Koch I, Kartzinel RY, Hogan A, Brubaker L, Wanser S, Stahler D, Wynne CDL, Ostrander EA, Sinsheimer JS, Udell MAR. Structural variants in genes associated with human Williams-Beuren syndrome underlie stereotypical hypersociability in domestic dogs. SciAdvances. Jul 19;3(7):e1700398. doi:10.1126/sciadv.1700398. 2017. [PubMed]

Parker HG, Dreger DL, Rimbault M, Davis BW, Mullen AM, Carpintero-Ramirez G, Ostrander EA.. Genomic analysis reveals the influence of geographic origin, immigration and cross-breed introgression on modern dog breed development. CellReports. Apr 25;19(4):697-708. doi:10.1016/j.celrep.2017.03.079. 2017. [PubMed]

Plassais J, Rimbault M, Williams FJ, Davis BW, Schoenebeck JJ, Ostrander EA. Analysis of large versus small dogs reveals three genes on the canine X chromosome associated with body weight, muscling and back fat thickness. PLoS Genet. Mar 3;13(3):e1006661. doi:10.1371/journal.pgen.1006661. 2017. [PubMed]

Parker HG, Harris A, Dreger DL, Ostrander EA. The bald and the beautiful: hairlessness in domestic dog breeds. PhilosophTransactRSocLondBBiolSci. Feb 5;372(1713):20150488. doi:10.1098/rstb.2015.0488. 2017. [PubMed]

Dreger DL, Rimbault M, Davis BW, Bhatnager A, Parker HG, Ostrander EA. Whole-genome sequence, SNP chips and pedigree structure: building demographic profiles in domestic dog breeds to optimize genetic-trait mapping. Dis Mod Mech. Dec 1;9(12):1445-1460. doi:10.1242/dmm.027037. 2016. [PubMed]

Decker B, Karyadi DM, Davis BW, Karlins E, Tillmans LS, Stanford JL, Thibodeau SN, Ostrander EA. Biallelic BRCA mutations shape the somatic mutational landscape of aggressive prostate tumors. Am J Hum Genet. May 5;98(5):818-829. doi:10.1016/j.ajhg.2016.03.003. 2016. [PubMed]

Decker B, Davis BW, Rimbault M, Long AH, Karlins E, Jagannathan V, Reiman R, Parker HG, Drögemüller C, Corneveaux JJ, Chapman ES, Trent JM, Leeb T, Huentelman JM, Wayne RK, Karyadi DM, Ostrander EA. Comparison against 186 canid whole-genome sequences reveals survival strategies of an ancient clonally transmissible canine tumor. GenomeRes. Nov;25(11):1646-55. doi:10.1101/gr,190314.115. 2015. [PubMed]

Decker B, Parker HG, Dhawan D, Kwon EM, Karlins E, Davis BW, Ramos-Vara JA, Bonney PL, McNiel EA, Knapp DW, Ostrander EA. Homologous mutation to human BRAF V600E is common in naturally occurring canine bladder cancer-evidence for a relevant model system and urine-based diagnostic test. Mol Canc Res. Jun;13(6):993-1002. doi:10.1158/1541-7786.MCR-14-0689. 2015. [PubMed]

Parker HG, Ostrander EA. Cancer. Hiding in plain view-an ancient dog in the modern world. Science. Jan 24;343(6169):376-8. doi:10.1126/science.1248812. 2014. [PubMed]

Rimbault M, Beale HC, Schoenebeck JJ, Hoopes BC, Allen JJ, Kilroy-Glynn P, Wayne RK, Sutter NB, Ostrander EA. Derived variants at six genes explain nearly half of size reduction in dog breeds. Genome Res. Dec;23(12):1985-95. doi:10.1101/gr.157339.113. 2013. [PubMed]

Karyadi DM, Karlins E, Decker B, vonHoldt BM, Carpintero-Ramirez G, Parker HG, Wayne RK, Ostrander EA. A copy number variant at the KITLG locus likely confers risk for canine squamous cell carcinoma of the digit. PLoSGenetics. Mar;9(3):e1003409. doi:10.1371/journal.pgen.1003409. 2013. [PubMed]

Schoenebeck JJ, Hutchinson SA, Byers A, Beale HC, Carrington B, Faden DL, Rimbault M, Decker B, Kidd JM, Sood R, Boyko AR, Fondon JW 3rd, Wayne RK, Bustamante CD, Ciruna B, Ostrander EA. Variation of BMP3 contributes to dog breed skull diversity. PLoSGenet. 8(8):e1002849. doi:10.1371/journal.pgen.1002849. 2012. [PubMed]

Huson HJ, vonHoldt BM, Rimbault M, Byers AM, Runstadler JA, Parker HG, Ostrander EA. Breed-specific ancestry studies and genome-wide association analysis highlight an association between the MYH9 gene and heat tolerance in Alaskan sprint racing sled dogs. MammGenome. Feb;23(1-2):178-94. doi:10.1007/s00335-011-9374-y. 2012. [PubMed]

Boyko AR, Quignon P, Li L, Schoenebeck JJ, Degenhardt JD, Lohmueller KE, Zhao K, Brisbin A, Parker HG, vonHoldt BM, Cargill M, Auton A, Reynolds A, Elkahloun AG, Castelhano M, Mosher DS, Sutter NB, Johnson GS, Novembre J, Hubisz MJ, Siepel A, Wayne RK, Bustamante CD, Ostrander EA. A simple genetic architecture underlies morphologic variation in dogs. PLoS Biol. Aug 10;8(8):e1000451. doi:10.1371/journal.pgen.1000451. 2010. [PubMed]

vonHoldt BM, Pollinger JP, Lohmueller KE, Han E, Parker HG, Quignon P, Degenhardt JD, Boyko AR, Earl DA, Auton A, Reynolds A, Bryc K, Brisbin A, Knowles JC, Mosher DS, Spady TC, Elkahloun A, Geffen E, Pilot M, Jedrzejewski W, Greco C, Randi E, Bannasch D, Wilton A, Shearman J, Musiani M, Cargill M, Jones PG, Qian Z, Huang W, Ding ZL, Zhang YP, Bustamante CD, Ostrander EA, Novembre J, Wayne RK. Genome-wide SNP and haplotype analyses reveal a rich history underlying dog domestication. Nature. Apr 8;464(7290):898-902. doi:10.1038/nature08837. 2010. [PubMed]

Cadieu E, Neff MW, Quignon P, Walsh K, Chase K, Parker HG, vonHoldt BM, Rhue A, Boyko A, Byers A, Wong A, Mosher DS, Elkahloun AG, Spady TC, André C, Lark KG, Cargill M, Bustamante CD, Wayne RK, Ostrander EA. Coat variation in the domestic dog is governed by variants in three genes. Science. Oct 2;326(5949):150-3. doi:10.1126/science.1177808. 2009. [PubMed]

Parker HG, vonHoldt BM, Quignon P, Margulies EH, Shao S, Mosher DS, Spady TC, Elkahloun A, Cargill M, Jones PG, Maslen CL, Acland GM, Sutter NB, Kuroki K, Bustamante CD, Wayne RK, Ostrander EA. An expressed Fgf4 retrogene is associated with breed-defining chondrodysplasia in domestic dogs. Science. Aug 21;325(5943):995-8. doi:10.1126/science.1173275. 2009. [PubMed]

Parker HG, Kukekova AV, Akey DT, Goldstein O, Kirkness EF, Baysac KC, Mosher DS, Aguirre GD, Acland GM, Ostrander EA. Breed relationships facilitate fine mapping studies: A 7.8 Kb deletion cosegregates with collie eye anomaly across multiple dog breeds. Genome Res. Nov;17(11):1562-71. doi:10.1101/gr.6772807. 2007. [PubMed]

Mosher DS, Quignon P, Bustamante CD, Sutter NB, Mellersh CS, Parker HG, Ostrander EA. A mutation in the myostatin gene increases muscle mass and enhances racing performance in heterozygote dogs. PLoS Genet. May 25;3(5):e79. doi:10.1371/journal.pgen.0030079. 2007. [PubMed]

Sutter NB, Bustamante CD, Chase K, Gray MM, Zhao K, Zhu L, Padhukasahasram B, Karlins E, Davis S, Jones PG, Quignon P, Johnson GS, Parker HG, Fretwell N, Mosher DS, Lawler DF, Satyaraj E, Nordborg M, Lark KG, Wayne RK, Ostrander EA. A single IGF1 Allele is a major determinant of small size in dogs. Science. Apr 6;316(5821):112-5. doi:10.1126/science.1137045. 2007. [PubMed]

Agalliu I, Kwon EM, Zadory D, McIntosh L, Thompson J, Stanford JL, Ostrander EA. Germline mutations in the BRCA2 gene and susceptibility to hereditary prostate cancer. Clin Cancer Res. Feb 1;13(3):839-43. doi:10.1158/1078-0432.CCR-06-2164. 2007. [PubMed]

Parker HG, Kruglyak L, Ostrander EA. Molecular genetics: DNA analysis of a putative dog clone. Nature. Mar 9;440(7081):E1-2. doi:10.1038/nature04685. 2006. [PubMed]

Sutter NB, Eberle MA, Parker HG, Pullar BJ, Kirkness EF, Kruglyak L, Ostrander EA. Extensive and breed specific linkage disequilibrium in Canis familiaris. Genome Res. Dec;14(12):2388-96. doi:10.1101/gr.3147604. 2004. [PubMed]

Parker HG, Kim LV, Sutter NB, Carlson S, Lorentzen TD, Malek TB, Johnson GS, DeFrance HB, Ostrander EA, Kruglyak L. Genetic structure of the purebred domestic dog. Science. May 21;304(5674):1160-4. doi:10.1126/science.1097406. 2004. [PubMed]

Lingaas F, Comstock KE, Kirkness EF, Sørensen A, Aarskaug T, Hitte C, Nickerson ML, Moe L, Schmidt LS, Thomas R, Breen M, Galibert F, Zbar B, Ostrander EA. A mutation in the canine BHD gene is associated with hereditary multifocal renal cystadenocarcinoma and nodular dermatofibrosis in the German Shepherd Dog. Hum Mol Genet. Dec 1;12(23):3043-53. doi:10.1093/hmg/ddg336. 2003. [PubMed]

Guyon R, Lorentzen TD, Hitte C, Kim L, Cadieu E, Parker HG, Quignon P, Lowe JK, Renier C, Gelfenbeyn B, Vignaux F, DeFrance HB, Gloux S, Mahairas GG, André C, Galibert F, Ostrander EA. A 1-Mb resolution radiation hybrid map of the canine genome. Proc Natl Acad Sci U S A. Apr 29;100(9):5296-301. doi:10.1073/pnas.0831002100. 2003. [PubMed]

Fleming MA, Potter JD, Ramirez CJ, Ostrander GK, Ostrander EA. Understanding missense mutations in the BRCA1 gene: an evolutionary approach. Proc Natl Acad Sci U S A. Feb 4;100(3):1151-6. doi:10.1073/pnas.0237285100. 2003. [PubMed]

Jónasdóttir TJ, Mellersh CS, Moe L, Heggebø R, Gamlem H, Ostrander EA, Lingaas F. Genetic mapping of a naturally occurring hereditary renal cancer syndrome in dogs. Proc Natl Acad Sci U S A. Apr 11;97(8):4132-7. doi:10.1073/pnas.070053397. 2000. [PubMed]

Malone KE, Daling JR, Thompson JD, O'Brien CA, Francisco LV, Ostrander EA. BRCA1 mutations and breast cancer in the general population: Analyses in women before age 35 years and in women before age 45 years with first-degree family history. J Am Med Assoc. Mar 25;279(12):922-9. doi:10.1001/jama.279.12.922. 1998. [PubMed]

Mellersh CS, Langston AA, Acland GM, Fleming MA, Ray K, Wiegand NA, Francisco LV, Gibbs M, Aguirre GD, Ostrander EA. A linkage map of the canine genome. Genomics. Dec 15;46(3):326-36. doi:10.1006/geno.1997.5098. 1997. [PubMed]

Langston AA, Malone KE, Thompson JD, Daling JR, Ostrander EA. BRCA1 mutations in a population-based sample of young women with breast cancer. N Engl J Med. Jan 18;334(3):137-42. doi:10.1056/NEJM199601183340301. 1996. [PubMed]