Elaine A Ostrander

National Human Genome Research Institute, Maryland, United States

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Publications (314)2504.33 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Fanconi anemia (FA) is a rare recessive disease resulting from mutations in one of at least 16 different genes. Mutation types and phenotypic manifestations of FA are highly heterogeneous and influence the clinical management of the disease. We analyzed 202 FA families for large deletions, using high-resolution Comparative Genome Hybridization arrays (arrayCGH), Single Nucleotide Polymorphism arrays (SNParrays) and DNA sequencing. We found pathogenic deletions in 88 FANCA, seven FANCC, two FANCD2, and one FANCB families. We find 35% of FA families carry large deletions, accounting for 18% of all FA pathogenic variants. Cloning and sequencing across the deletion breakpoints revealed that 52 FANCA deletion ends, and one FANCC deletion end extended beyond the gene boundaries, potentially affecting neighboring genes with phenotypic consequences. Seventy-five percent of the FANCA deletions are Alu-Alu mediated, predominantly by AluY elements, and appear to be caused by Non-Allelic Homologous Recombination. Individual Alu hotspots were identified. Defining the haplotypes of four FANCA deletions shared by multiple families revealed that three share a common ancestry. Knowing the exact molecular changes that lead to the disease may be critical for a better understanding of the FA phenotype, and to gain insight into the mechanisms driving these pathogenic deletion variants.This article is protected by copyright. All rights reserved
    Human Mutation 08/2014; · 5.21 Impact Factor
  • Jeffrey J Schoenebeck, Elaine A Ostrander
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    ABSTRACT: Although most modern dog breeds are less than 200 years old, the symbiosis between man and dog is ancient. Since prehistoric times, repeated selection events have transformed the wolf into man's guardians, laborers, athletes, and companions. The rapid transformation from pack predator to loyal companion is a feat that is arguably unique among domesticated animals. How this transformation came to pass remained a biological mystery until recently: Within the past decade, the deployment of genomic approaches to study population structure, detect signatures of selection, and identify genetic variants that underlie canine phenotypes is ushering into focus novel biological mechanisms that make dogs remarkable. Ironically, the very practices responsible for breed formation also spurned morbidity; today, many diseases are correlated with breed identity. In this review, we discuss man's best friend in the context of a genetic model to understand paradigms of heritable phenotypes, both desirable and disadvantageous. Expected final online publication date for the Annual Review of Cell and Developmental Biology Volume 30 is October 06, 2014. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates.
    Annual Review of Cell and Developmental Biology 07/2014; · 17.98 Impact Factor
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    ABSTRACT: Background. One challenge in prostate cancer (PCa) is distinguishing indolent from aggressive disease at diagnosis. DNA promoter hypermethylation is a frequent epigenetic event in PCa, but few studies of DNA methylation in relation to features of more aggressive tumors or PCa recurrence have been completed. Methods. We used the Infinium® HumanMethylation450 BeadChip to assess DNA methylation in tumor tissue from 407 patients with clinically localized PCa who underwent radical prostatectomy. Recurrence status was determined by follow-up surveys, medical record review, and linkage with the SEER registry. The methylation status of 14 genes for which promoter hypermethylation was previously correlated with advanced disease or biochemical recurrence was evaluated. Average methylation level for promoter region CpGs in patients who recurred compared to those with no evidence of recurrence was analyzed. For two genes with differential methylation, time to recurrence was examined. Results. During an average follow-up of 11.7 years, 104 (26%) patients recurred. Significant promoter hypermethylation in at least 50% of CpG sites in two genes, ABHD9 and HOXD3, was found in tumors from patients who recurred compared to those without recurrence. Evidence was strongest for HOXD3 (lowest P = 9.46x10-6), with higher average methylation across promoter region CpGs associated with reduced recurrence-free survival (P = 2x10-4). DNA methylation profiles did not differ by recurrence status for the other genes. Conclusions. These results validate the association between promoter hypermethylation of ADHB9 and HOXD3 and PCa recurrence. Impact. Tumor DNA methylation profiling may help distinguish PCa patients at higher risk for disease recurrence.
    Cancer Epidemiology Biomarkers &amp Prevention 04/2014; · 4.56 Impact Factor
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    ABSTRACT: Previous GWAS studies have reported significant associations between various common SNPs and prostate cancer risk using cases unselected for family history. How these variants influence risk in familial prostate cancer is not well studied. Here, we analyzed 25 previously reported SNPs across 14 loci from prior prostate cancer GWAS. The International Consortium for Prostate Cancer Genetics (ICPCG) previously validated some of these using a family-based association method (FBAT). However, this approach suffered reduced power due to the conditional statistics implemented in FBAT. Here, we use a case-control design with an empirical analysis strategy to analyze the ICPCG resource for association between these 25 SNPs and familial prostate cancer risk. Fourteen sites contributed 12,506 samples (9,560 prostate cancer cases, 3,368 with aggressive disease, and 2,946 controls from 2,283 pedigrees). We performed association analysis with Genie software which accounts for relationships. We analyzed all familial p
    Hum.Genet. 03/2014; 133(3):347-356.
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    ABSTRACT: Previous GWAS studies have reported significant associations between various common SNPs and prostate cancer risk using cases unselected for family history. How these variants influence risk in familial prostate cancer is not well studied. Here, we analyzed 25 previously reported SNPs across 14 loci from prior prostate cancer GWAS. The International Consortium for Prostate Cancer Genetics (ICPCG) previously validated some of these using a family-based association method (FBAT). However, this approach suffered reduced power due to the conditional statistics implemented in FBAT. Here, we use a case–control design with an empirical analysis strategy to analyze the ICPCG resource for association between these 25 SNPs and familial prostate cancer risk. Fourteen sites contributed 12,506 samples (9,560 prostate cancer cases, 3,368 with aggressive disease, and 2,946 controls from 2,283 pedigrees). We performed association analysis with Genie software which accounts for relationships. We analyzed all familial prostate cancer cases and the subset of aggressive cases. For the familial prostate cancer phenotype, 20 of the 25 SNPs were at least nominally associated with prostate cancer and 16 remained significant after multiple testing correction (p ≤ 1E −3) occurring on chromosomal bands 6q25, 7p15, 8q24, 10q11, 11q13, 17q12, 17q24, and Xp11. For aggressive disease, 16 of the SNPs had at least nominal evidence and 8 were statistically significant including 2p15. The results indicate that the majority of common, low-risk alleles identified in GWAS studies for all prostate cancer also contribute risk for familial prostate cancer, and that some may contribute risk to aggressive disease.
    Human Genetics 03/2014; · 4.63 Impact Factor
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    ABSTRACT: The HOXB13 gene has been implicated in prostate cancer (PrCa) susceptibility. We performed a high resolution fine-mapping analysis to comprehensively evaluate the association between common genetic variation across the HOXB genetic locus at 17q21 and PrCa risk. This involved genotyping 700 SNPs using a custom Illumina iSelect array (iCOGS) followed by imputation of 3195 SNPs in 20,440 PrCa cases and 21,469 controls in The PRACTICAL consortium. We identified a cluster of highly correlated common variants situated within or closely upstream of HOXB13 that were significantly associated with PrCa risk, described by rs117576373 (OR 1.30, P = 2.62×10(-14)). Additional genotyping, conditional regression and haplotype analyses indicated that the newly identified common variants tag a rare, partially correlated coding variant in the HOXB13 gene (G84E, rs138213197), which has been identified recently as a moderate penetrance PrCa susceptibility allele. The potential for GWAS associations detected through common SNPs to be driven by rare causal variants with higher relative risks has long been proposed; however, to our knowledge this is the first experimental evidence for this phenomenon of synthetic association contributing to cancer susceptibility.
    PLoS Genetics 02/2014; 10(2):e1004129. · 8.52 Impact Factor
  • Heidi G Parker, Elaine A Ostrander
    Science 01/2014; 343(6169):376-8. · 31.20 Impact Factor
  • Brian W Davis, Elaine A Ostrander
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    ABSTRACT: Domestic dogs are unique from other animal models of cancer in that they generally experience spontaneous disease. In addition, most types of cancer observed in humans are found in dogs, suggesting that canines may be an informative system for the study of cancer genetics. Domestic dogs are divided into over 175 breeds, with members of each breed sharing significant phenotypes. The breed barrier enhances the utility of the model, especially for genetic studies where small numbers of genes are hypothesized to account for the breed cancer susceptibility. These facts, combined with recent advances in high-throughput sequencing technologies allows for an unrivaled ability to use pet dog populations to find often subtle mutations that promote cancer susceptibility and progression in dogs as a whole. The meticulous record keeping associated with dog breeding makes the model still more powerful, as it facilitates both association analysis and family-based linkage studies. Key to the success of these studies is their cooperative nature, with owners, scientists, veterinarians and breed clubs working together to avoid the cost and unpopularity of developing captive populations. In this article we explore these principals and advocate for colony-free, genetic studies that will enhance our ability to diagnose and treat cancer in dogs and humans alike.
    ILAR journal / National Research Council, Institute of Laboratory Animal Resources 01/2014; 55(1):59-68. · 1.58 Impact Factor
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    Brennan Decker, Elaine A Ostrander
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    ABSTRACT: Prostate cancer (PC) is the most common noncutaneous cancer in men, and epidemiological studies suggest that about 40% of PC risk is heritable. Linkage analyses in hereditary PC families have identified multiple putative loci. However, until recently, identification of specific risk alleles has proven elusive. Cooney et al used linkage mapping and segregation analysis to identify a putative risk locus on chromosome 17q21-22. In search of causative variant(s) in genes from the candidate region, a novel, potentially deleterious G84E substitution in homeobox transcription factor gene HOXB13 was observed in multiple hereditary PC families. In follow-up testing, the G84E allele was enriched in cases, especially those with an early diagnosis or positive family history of disease. This finding was replicated by others, confirming HOXB13 as a PC risk gene. The HOXB13 protein plays diverse biological roles in embryonic development and terminally differentiated tissue. In tumor cell lines, HOXB13 participates in a number of biological functions, including coactivation and localization of the androgen receptor and FOXA1. However, no consensus role has emerged and many questions remain. All HOXB13 variants with a proposed role in PC risk are predicted to damage the protein and lie in domains that are highly conserved across species. The G84E variant has the strongest epidemiological support and lies in a highly conserved MEIS protein-binding domain, which binds cofactors required for activation. On the basis of epidemiological and biological data, the G84E variant likely modulates the interaction between the HOXB13 protein and the androgen receptor, as well as affecting FOXA1-mediated transcriptional programming. However, further studies of the mutated protein are required to clarify the mechanisms by which this translates into PC risk.
    Pharmacogenomics and personalized medicine. 01/2014; 7:193-201.
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    ABSTRACT: To identify genetic changes underlying dog domestication and reconstruct their early evolutionary history, we generated high-quality genome sequences from three gray wolves, one from each of the three putative centers of dog domestication, two basal dog lineages (Basenji and Dingo) and a golden jackal as an outgroup. Analysis of these sequences supports a demographic model in which dogs and wolves diverged through a dynamic process involving population bottlenecks in both lineages and post-divergence gene flow. In dogs, the domestication bottleneck involved at least a 16-fold reduction in population size, a much more severe bottleneck than estimated previously. A sharp bottleneck in wolves occurred soon after their divergence from dogs, implying that the pool of diversity from which dogs arose was substantially larger than represented by modern wolf populations. We narrow the plausible range for the date of initial dog domestication to an interval spanning 11-16 thousand years ago, predating the rise of agriculture. In light of this finding, we expand upon previous work regarding the increase in copy number of the amylase gene (AMY2B) in dogs, which is believed to have aided digestion of starch in agricultural refuse. We find standing variation for amylase copy number variation in wolves and little or no copy number increase in the Dingo and Husky lineages. In conjunction with the estimated timing of dog origins, these results provide additional support to archaeological finds, suggesting the earliest dogs arose alongside hunter-gathers rather than agriculturists. Regarding the geographic origin of dogs, we find that, surprisingly, none of the extant wolf lineages from putative domestication centers is more closely related to dogs, and, instead, the sampled wolves form a sister monophyletic clade. This result, in combination with dog-wolf admixture during the process of domestication, suggests that a re-evaluation of past hypotheses regarding dog origins is necessary.
    PLoS Genetics 01/2014; 10(1):e1004016. · 8.52 Impact Factor
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    ABSTRACT: Genomic resources developed for domesticated species provide powerful tools for studying the evolutionary history of their wild relatives. Here we use 61K single-nucleotide polymorphisms (SNPs) evenly spaced throughout the canine nuclear genome to analyse evolutionary relationships among the three largest European populations of grey wolves in comparison with other populations worldwide, and investigate genome-wide effects of demographic bottlenecks and signatures of selection. European wolves have a discontinuous range, with large and connected populations in Eastern Europe and relatively smaller, isolated populations in Italy and the Iberian Peninsula. Our results suggest a continuous decline in wolf numbers in Europe since the Late Pleistocene, and long-term isolation and bottlenecks in the Italian and Iberian populations following their divergence from the Eastern European population. The Italian and Iberian populations have low genetic variability and high linkage disequilibrium, but relatively few autozygous segments across the genome. This last characteristic clearly distinguishes them from populations that underwent recent drastic demographic declines or founder events, and implies long-term bottlenecks in these two populations. Although genetic drift due to spatial isolation and bottlenecks seems to be a major evolutionary force diversifying the European populations, we detected 35 loci that are putatively under diversifying selection. Two of these loci flank the canine platelet-derived growth factor gene, which affects bone growth and may influence differences in body size between wolf populations. This study demonstrates the power of population genomics for identifying genetic signals of demographic bottlenecks and detecting signatures of directional selection in bottlenecked populations, despite their low background variability.Heredity advance online publication, 18 December 2013; doi:10.1038/hdy.2013.122.
    Heredity 12/2013; · 4.11 Impact Factor
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    ABSTRACT: Selective breeding of dogs by humans has generated extraordinary diversity in body size. A number of multibreed analyses have been undertaken to identify the genetic basis of this diversity. We analyzed four loci discovered in a previous genome-wide association study that used 60,968 SNPs to identify size-associated genomic intervals, which were too large to assign causative roles to genes. First, we performed fine-mapping to define critical intervals that included the candidate genes GHR, HMGA2, SMAD2 and STC2, identifying five highly associated markers at the four loci. We hypothesize that three of the variants are likely to be causative variants. We then genotyped each marker, together with previously reported size-associated variants in the IGF1 and IGF1R genes, on a panel of 500 domestic dogs from 93 breeds and identified the ancestral allele by genotyping the same markers on 30 wild canids. We observed that the derived alleles at all markers correlated with reduced body size, and smaller dogs are more likely to carry derived alleles at multiple markers. However, breeds are not generally fixed at all markers; multiple combinations of genotypes are found within most breeds. Finally, we show that 46-52.5% of the variance in body size of dog breeds can be explained by seven markers in proximity to exceptional candidate genes. Among breeds with standard weights < 41 kg (90 lbs), the genotypes accounted for 64.3% of variance in weight. The size variation for dog breeds ≥ 41 kg is not explained by these six genes; additional genes that contribute to gigantism remain to be found. This work advances our understanding of mammalian growth by describing genetic contributions to canine size determination in non-giant dog breeds.
    Genome Research 09/2013; · 14.40 Impact Factor
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    ABSTRACT: Background: Rare, inherited mutations account for 5%-10% of all prostate cancer (PCa) cases. However, to date, few causative mutations have been identified. Methods: To identify rare mutations for PCa, we performed whole-exome sequencing (WES) in multiple kindreds (n = 91) from 19 hereditary prostate cancer (HPC) families characterized by aggressive or early onset phenotypes. Candidate variants (n = 130) identified through family- and bioinformatics-based filtering of WES data were then genotyped in an independent set of 270 HPC families (n = 819 PCa cases; n = 496 unaffected relatives) for replication. Two variants with supportive evidence were subsequently genotyped in a population-based case-control study (n = 1,155 incident PCa cases; n = 1,060 age-matched controls) for further confirmation. All participants were men of European ancestry. Results: The strongest evidence was for two germline missense variants in the butyrophilin-like 2 (BTNL2) gene (rs41441651, p.Asp336Asn and rs28362675, p.Gly454Cys) that segregated with affection status in two of the WES families. In the independent set of 270 HPC families, 1.5% (rs41441651; P = 0.0032) and 1.2% (rs28362675; P = 0.0070) of affected men, but no unaffected men, carried a variant. Both variants were associated with elevated PCa risk in the population-based study (rs41441651: OR = 2.7; 95% CI, 1.27-5.87; P = 0.010; rs28362675: OR = 2.5; 95% CI, 1.16-5.46; P = 0.019). Conclusions: Results indicate that rare BTNL2 variants play a role in susceptibility to both familial and sporadic prostate cancer. Impact: Results implicate BTNL2 as a novel PCa susceptibility gene.
    Cancer Epidemiology Biomarkers &amp Prevention 07/2013; · 4.56 Impact Factor
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    ABSTRACT: To identify genetic changes underlying dog domestication and reconstruct their early evolutionary history, we analyzed novel high-quality genome sequences of three gray wolves, one from each of three putative centers of dog domestication, two ancient dog lineages (Basenji and Dingo) and a golden jackal as an outgroup. We find dogs and wolves diverged through a dynamic process involving population bottlenecks in both lineages and post-divergence gene flow, which confounds previous inferences of dog origins. In dogs, the domestication bottleneck was severe involving a 17 to 49-fold reduction in population size, a much stronger bottleneck than estimated previously from less intensive sequencing efforts. A sharp bottleneck in wolves occurred soon after their divergence from dogs, implying that the pool of diversity from which dogs arose was far larger than represented by modern wolf populations. Conditional on mutation rate, we narrow the plausible range for the date of initial dog domestication to an interval from 11 to 16 thousand years ago. This period predates the rise of agriculture, implying that the earliest dogs arose alongside hunter-gathers rather than agriculturists. Regarding the geographic origin of dogs, we find that surprisingly, none of the extant wolf lineages from putative domestication centers are more closely related to dogs, and the sampled wolves instead form a sister monophyletic clade. This result, in combination with our finding of dog-wolf admixture during the process of domestication, suggests a re-evaluation of past hypotheses of dog origin is necessary. Finally, we also detect signatures of selection, including evidence for selection on genes implicated in morphology, metabolism, and neural development. Uniquely, we find support for selective sweeps at regulatory sites suggesting gene regulatory changes played a critical role in dog domestication.
    05/2013;
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    ABSTRACT: Current methods for detecting mutations in Fanconi anemia (FA) suspected patients are inefficient and often miss mutations. We have applied recent advances in DNA sequencing and genomic capture to the diagnosis of FA. Specifically, we used custom Molecular Inversion Probes or TruSeq-enrichment oligos to capture and sequence FA and related genes, including introns, from 27 samples from the International Fanconi Anemia Registry at the Rockefeller University. DNA sequencing was complemented with custom Array Comparative Genomic Hybridization (aCGH) and RNA-Seq analysis. aCGH identified deletions/duplications in four different FA genes. RNA-Seq analysis revealed lack of allele specific expression associated with a deletion, and splicing defects caused by missense, synonymous, and deep-in-intron variants. The combination of TruSeq targeted capture, aCGH and RNA-Seq enabled us to identify the complementation group and biallelic germline mutations in all 27 families: FANCA (7), FANCB (3), FANCC (3), FANCD1 (1), FANCD2 (3), FANCF (2), FANCG (2), FANCI (1), FANCJ (2) and FANCL (3). FANCC mutations are often the cause of FA in patients of Ashkenazi Jewish (AJ) ancestry, and we identified two novel FANCC mutations in two patients of AJ ancestry. We describe here a strategy for efficient molecular diagnosis of Fanconi anemia.
    Blood 04/2013; · 9.78 Impact Factor
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    ABSTRACT: Prostate cancer is the most frequently diagnosed cancer in males in developed countries. To identify common prostate cancer susceptibility alleles, we genotyped 211,155 SNPs on a custom Illumina array (iCOGS) in blood DNA from 25,074 prostate cancer cases and 24,272 controls from the international PRACTICAL Consortium. Twenty-three new prostate cancer susceptibility loci were identified at genome-wide significance (P < 5 × 10(-8)). More than 70 prostate cancer susceptibility loci, explaining ∼30% of the familial risk for this disease, have now been identified. On the basis of combined risks conferred by the new and previously known risk loci, the top 1% of the risk distribution has a 4.7-fold higher risk than the average of the population being profiled. These results will facilitate population risk stratification for clinical studies.
    Nature Genetics 03/2013; 45(4):385-391. · 35.21 Impact Factor
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    ABSTRACT: Associations between single nucleotide polymorphisms (SNPs) at 5p15 and multiple cancer types have been reported. We have previously shown evidence for a strong association between prostate cancer (PrCa) risk and rs2242652 at 5p15, intronic in the telomerase reverse transcriptase (TERT) gene that encodes TERT. To comprehensively evaluate the association between genetic variation across this region and PrCa, we performed a fine-mapping analysis by genotyping 134 SNPs using a custom Illumina iSelect array or Sequenom MassArray iPlex, followed by imputation of 1094 SNPs in 22 301 PrCa cases and 22 320 controls in The PRACTICAL consortium. Multiple stepwise logistic regression analysis identified four signals in the promoter or intronic regions of TERT that independently associated with PrCa risk. Gene expression analysis of normal prostate tissue showed evidence that SNPs within one of these regions also associated with TERT expression, providing a potential mechanism for predisposition to disease.
    Human Molecular Genetics 03/2013; · 7.69 Impact Factor
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    ABSTRACT: The causative mutation for the black-and-tan (a(t)) phenotype in dogs was previously shown to be a SINE insertion in the 5' region of Agouti Signaling Protein (ASIP). Dogs with the black-and-tan phenotype, as well as dogs with the saddle tan phenotype, genotype as a(t)/_ at this locus. We have identified a 16-bp duplication (g.1875_1890dupCCCCAGGTCAGAGTTT) in an intron of hnRNP associated with lethal yellow (RALY), which segregates with the black-and-tan phenotype in a group of 99 saddle tan and black-and-tan Basset Hounds and Pembroke Welsh Corgis. In these breeds, all dogs with the saddle tan phenotype had RALY genotypes of +/+ or +/dup, whereas dogs with the black-and-tan phenotype were homozygous for the duplication. The presence of an a(y)/_ fawn or e/e red genotype is epistatic to the +/_ saddle tan genotype. Genotypes from 10 wolves and 1 coyote indicated that the saddle tan (+) allele is the ancestral allele, suggesting that black-and-tan is a modification of saddle tan. An additional 95 dogs from breeds that never have the saddle tan phenotype have all three of the possible RALY genotypes. We suggest that a multi-gene interaction involving ASIP, RALY, MC1R, DEFB103, and a yet-unidentified modifier gene is required for expression of saddle tan.
    The Journal of heredity 03/2013; · 2.05 Impact Factor
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    ABSTRACT: The domestic dog is a robust model for studying the genetics of complex disease susceptibility. The strategies used to develop and propagate modern breeds have resulted in an elevated risk for specific diseases in particular breeds. One example is that of Standard Poodles (STPOs), who have increased risk for squamous cell carcinoma of the digit (SCCD), a locally aggressive cancer that causes lytic bone lesions, sometimes with multiple toe recurrence. However, only STPOs of dark coat color are at high risk; light colored STPOs are almost entirely unaffected, suggesting that interactions between multiple pathways are necessary for oncogenesis. We performed a genome-wide association study (GWAS) on STPOs, comparing 31 SCCD cases to 34 unrelated black STPO controls. The peak SNP on canine chromosome 15 was statistically significant at the genome-wide level (Praw = 1.60×10(-7); Pgenome = 0.0066). Additional mapping resolved the region to the KIT Ligand (KITLG) locus. Comparison of STPO cases to other at-risk breeds narrowed the locus to a 144.9-Kb region. Haplotype mapping among 84 STPO cases identified a minimal region of 28.3 Kb. A copy number variant (CNV) containing predicted enhancer elements was found to be strongly associated with SCCD in STPOs (P = 1.72×10(-8)). Light colored STPOs carry the CNV risk alleles at the same frequency as black STPOs, but are not susceptible to SCCD. A GWAS comparing 24 black and 24 light colored STPOs highlighted only the MC1R locus as significantly different between the two datasets, suggesting that a compensatory mutation within the MC1R locus likely protects light colored STPOs from disease. Our findings highlight a role for KITLG in SCCD susceptibility, as well as demonstrate that interactions between the KITLG and MC1R loci are potentially required for SCCD oncogenesis. These findings highlight how studies of breed-limited diseases are useful for disentangling multigene disorders.
    PLoS Genetics 03/2013; 9(3):e1003409. · 8.52 Impact Factor
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Publication Stats

12k Citations
2,504.33 Total Impact Points

Institutions

  • 2005–2014
    • National Human Genome Research Institute
      Maryland, United States
    • Université de Rennes 1
      • Faculté de Médecine
      Rennes, Brittany, France
  • 2011–2013
    • Wake Forest School of Medicine
      Winston-Salem, North Carolina, United States
    • Northwestern University
      • Department of Urology
      Evanston, IL, United States
  • 2008–2013
    • Institute of Cancer Research
      Londinium, England, United Kingdom
  • 1993–2013
    • Fred Hutchinson Cancer Research Center
      • • Institute for Prostate Cancer Research
      • • Epidemiology Program
      • • Division of Public Health Sciences
      • • Division of Clinical Research
      • • Division of Human Biology
      • • Transplantation Biology Program
      Seattle, Washington, United States
  • 2006–2012
    • National Institutes of Health
      • Branch of Cancer Genetics
      Bethesda, MD, United States
    • Rice University
      • Department of Ecology and Evolutionary Biology
      Houston, TX, United States
  • 1999–2012
    • University of California, Los Angeles
      • Department of Ecology and Evolutionary Biology
      Los Angeles, CA, United States
    • University of Pennsylvania
      • School of Veterinary Medicine
      Philadelphia, PA, United States
  • 1996–2010
    • University of Washington Seattle
      • • Department of Urology
      • • Division of Medical Genetics
      • • Department of Epidemiology
      Seattle, WA, United States
  • 2009
    • Yale-New Haven Hospital
      • Department of Pathology
      New Haven, Connecticut, United States
    • Albert Einstein College of Medicine
      • Department of Epidemiology & Population Health
      New York City, NY, United States
    • University of California, San Francisco
      San Francisco, California, United States
    • Boston Scientific
      Boston, Massachusetts, United States
  • 2007–2009
    • University of Cambridge
      • • Department of Public Health and Primary Care
      • • Department of Veterinary Medicine
      Cambridge, ENG, United Kingdom
  • 1997–2009
    • University of Utah
      • • Department of Biology
      • • Division of Genetic Epidemiology
      Salt Lake City, UT, United States
  • 2007–2008
    • Mayo Clinic - Rochester
      • Department of Health Science Research
      Rochester, Minnesota, United States
  • 2003–2008
    • French National Centre for Scientific Research
      Lutetia Parisorum, Île-de-France, France
    • Norwegian School of Veterinary Science
      Kristiania (historical), Oslo County, Norway
  • 2004
    • North Carolina State University
      • Department of Molecular Biomedical Sciences
      Raleigh, NC, United States
  • 1998–2003
    • Cornell University
      • College of Veterinary Medicine
      Ithaca, NY, United States
  • 2002
    • University of Wyoming
      • Department of Zoology and Physiology
      Laramie, WY, United States
    • Jules Stein Eye Institute
      Maryland, United States
  • 2001
    • Medical Research Council (UK)
      Londinium, England, United Kingdom
  • 1992–1999
    • University of California, Berkeley
      • Department of Molecular and Cell Biology
      Berkeley, MO, United States
  • 1994
    • Zoological Society of London
      • Institute of Zoology
      London, ENG, United Kingdom
  • 1993–1994
    • Lawrence Berkeley National Laboratory
      Berkeley, California, United States