ORCID Profile
0000-0001-6075-9738
Current Organisation
National Institutes of Health
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Publisher: Springer Science and Business Media LLC
Date: 05-11-2018
DOI: 10.1038/S41467-018-06863-1
Abstract: Chromosome 8q24 is a susceptibility locus for multiple cancers, including prostate cancer. Here we combine genetic data across the 8q24 susceptibility region from 71,535 prostate cancer cases and 52,935 controls of European ancestry to define the overall contribution of germline variation at 8q24 to prostate cancer risk. We identify 12 independent risk signals for prostate cancer ( p 4.28 × 10 −15 ), including three risk variants that have yet to be reported. From a polygenic risk score (PRS) model, derived to assess the cumulative effect of risk variants at 8q24, men in the top 1% of the PRS have a 4-fold (95%CI = 3.62–4.40) greater risk compared to the population average. These 12 variants account for ~25% of what can be currently explained of the familial risk of prostate cancer by known genetic risk factors. These findings highlight the overwhelming contribution of germline variation at 8q24 on prostate cancer risk which has implications for population risk stratification.
Publisher: Springer Science and Business Media LLC
Date: 21-04-2010
DOI: 10.1038/EJHG.2010.49
Publisher: Oxford University Press (OUP)
Date: 14-07-2010
DOI: 10.1093/HMG/DDQ283
Publisher: Elsevier BV
Date: 06-2021
Publisher: Oxford University Press (OUP)
Date: 18-10-2016
DOI: 10.1093/HMG/DDW349
Publisher: Wiley
Date: 29-05-2023
DOI: 10.1111/MEC.16998
Abstract: Admixture between species is a cause for concern in wildlife management. Canids are particularly vulnerable to interspecific hybridisation, and genetic admixture has shaped their evolutionary history. Microsatellite DNA testing, relying on a small number of genetic markers and geographically restricted reference populations, has identified extensive domestic dog admixture in Australian dingoes and driven conservation management policy. But there exists a concern that geographic variation in dingo genotypes could confound ancestry analyses that use a small number of genetic markers. Here, we apply genome‐wide single‐nucleotide polymorphism (SNP) genotyping to a set of 402 wild and captive dingoes collected from across Australia and then carry out comparisons to domestic dogs. We then perform ancestry modelling and biogeographic analyses to characterise population structure in dingoes and investigate the extent of admixture between dingoes and dogs in different regions of the continent. We show that there are at least five distinct dingo populations across Australia. We observed limited evidence of dog admixture in wild dingoes. Our work challenges previous reports regarding the occurrence and extent of dog admixture in dingoes, as our ancestry analyses show that previous assessments severely overestimate the degree of domestic dog admixture in dingo populations, particularly in south‐eastern Australia. These findings strongly support the use of genome‐wide SNP genotyping as a refined method for wildlife managers and policymakers to assess and inform dingo management policy and legislation moving forwards.
Publisher: Proceedings of the National Academy of Sciences
Date: 15-03-2021
Publisher: American Association for Cancer Research (AACR)
Date: 08-2008
DOI: 10.1158/1055-9965.EPI-08-0317
Abstract: A recent genome-wide association study found that genetic variants on chromosomes 3, 6, 7, 10, 11, 19 and X were associated with prostate cancer risk. We evaluated the most significant single-nucleotide polymorphisms (SNP) in these loci using a worldwide consortium of 13 groups (PRACTICAL). Blood DNA from 7,370 prostate cancer cases and 5,742 male controls was analyzed by genotyping assays. Odds ratios (OR) associated with each genotype were estimated using unconditional logistic regression. Six of the seven SNPs showed clear evidence of association with prostate cancer (P = 0.0007-P = 10−17). For each of these six SNPs, the estimated per-allele OR was similar to those previously reported and ranged from 1.12 to 1.29. One SNP on 3p12 (rs2660753) showed a weaker association than previously reported [per-allele OR, 1.08 (95% confidence interval, 1.00-1.16 P = 0.06) versus 1.18 (95% confidence interval, 1.06-1.31)]. The combined risks associated with each pair of SNPs were consistent with a multiplicative risk model. Under this model, and in combination with previously reported SNPs on 8q and 17q, these loci explain 16% of the familial risk of the disease, and men in the top 10% of the risk distribution have a 2.1-fold increased risk relative to general population rates. This study provides strong confirmation of these susceptibility loci in multiple populations and shows that they make an important contribution to prostate cancer risk prediction. (Cancer Epidemiol Biomarkers Prev 2008 (8):2052–61)
Publisher: Springer Science and Business Media LLC
Date: 03-01-2018
Publisher: Springer Science and Business Media LLC
Date: 20-01-2021
Publisher: Oxford University Press (OUP)
Date: 13-10-2018
DOI: 10.1093/GBE/EVY229
Publisher: Proceedings of the National Academy of Sciences
Date: 31-08-2020
Abstract: New Guinea singing dogs (NGSD) are distinctive among the Canidae because of their unique and characteristic vocalization, isolated habitat, and status as a rare representative of wild dogs. Their scarcity, combined with the knowledge that none have been captured or exported since the late 1970s, supports the hypothesis that NGSD are extinct in the wild. We have analyzed the nuclear genome of the first dogs captured from the highlands of Papua in approximately 50 y. We provide DNA-based evidence for an ancestral relationship between highland wild dogs (HWD) and captive NGSD suggesting that the founding population of the NGSD is not, in fact, extinct and that HWD should be resourced for conservation efforts to rebuild this unique canid population.
Publisher: American Association for Cancer Research (AACR)
Date: 09-2011
DOI: 10.1158/1055-9965.EPI-11-0236
Abstract: Background: Prostate cancer is the second leading cause of cancer-related deaths in men, accounting for more than 30,000 deaths annually. The purpose of this study was to test whether variation in selected candidate genes in biological pathways of interest for prostate cancer progression could help distinguish patients at higher risk for fatal prostate cancer. Methods: In this hypothesis-driven study, we genotyped 937 single nucleotide polymorphisms (SNPs) in 156 candidate genes in a population-based cohort of 1,309 prostate cancer patients. We identified 22 top-ranking SNPs (P ≤ 0.01, FDR ≤ 0.70) associated with prostate cancer-specific mortality (PCSM). A subsequent validation study was completed in an independent population-based cohort of 2,875 prostate cancer patients. Results: Five SNPs were validated (P ≤ 0.05) as being significantly associated with PCSM, one each in the LEPR, CRY1, RNASEL, IL4, and ARVCF genes. Compared with patients with 0 to 2 of the at-risk genotypes those with 4 to 5 at-risk genotypes had a 50% (95% CI, 1.2–1.9) higher risk of PCSM and risk increased with the number of at-risk genotypes carried (Ptrend = 0.001), adjusting for clinicopathologic factors known to influence prognosis. Conclusion: Five genetic markers were validated to be associated with lethal prostate cancer. Impact: This is the first population-based study to show that germline genetic variants provide prognostic information for prostate cancer-specific survival. The clinical utility of this five-SNP panel to stratify patients at higher risk for adverse outcomes should be evaluated. Cancer Epidemiol Biomarkers Prev 20(9) 1928–36. ©2011 AACR.
Publisher: Public Library of Science (PLoS)
Date: 13-02-2014
Publisher: American Association for Cancer Research (AACR)
Date: 07-2015
DOI: 10.1158/1055-9965.EPI-14-0317
Abstract: Background: Genome-wide association studies have identified multiple genetic variants associated with prostate cancer risk which explain a substantial proportion of familial relative risk. These variants can be used to stratify in iduals by their risk of prostate cancer. Methods: We genotyped 25 prostate cancer susceptibility loci in 40,414 in iduals and derived a polygenic risk score (PRS). We estimated empirical odds ratios (OR) for prostate cancer associated with different risk strata defined by PRS and derived age-specific absolute risks of developing prostate cancer by PRS stratum and family history. Results: The prostate cancer risk for men in the top 1% of the PRS distribution was 30.6 (95% CI, 16.4–57.3) fold compared with men in the bottom 1%, and 4.2 (95% CI, 3.2–5.5) fold compared with the median risk. The absolute risk of prostate cancer by age of 85 years was 65.8% for a man with family history in the top 1% of the PRS distribution, compared with 3.7% for a man in the bottom 1%. The PRS was only weakly correlated with serum PSA level (correlation = 0.09). Conclusions: Risk profiling can identify men at substantially increased or reduced risk of prostate cancer. The effect size, measured by OR per unit PRS, was higher in men at younger ages and in men with family history of prostate cancer. Incorporating additional newly identified loci into a PRS should improve the predictive value of risk profiles. Impact: We demonstrate that the risk profiling based on SNPs can identify men at substantially increased or reduced risk that could have useful implications for targeted prevention and screening programs. Cancer Epidemiol Biomarkers Prev 24(7) 1121–9. ©2015 AACR.
Publisher: Elsevier BV
Date: 08-2021
Publisher: American Association for Cancer Research (AACR)
Date: 09-2013
DOI: 10.1158/1055-9965.EPI-13-0345
Abstract: Background: Rare, inherited mutations account for 5% to 10% of all prostate cancer cases. However, to date, few causative mutations have been identified. Methods: To identify rare mutations for prostate cancer, we conducted 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 prostate cancer 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 prostate cancer 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 prostate cancer 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 prostate cancer susceptibility gene. Cancer Epidemiol Biomarkers Prev 22(9) 1520–8. ©2013 AACR.
Publisher: Cold Spring Harbor Laboratory
Date: 13-04-2022
DOI: 10.1101/2022.04.11.22273677
Abstract: Knowledge of rare, inherited variants in DNA damage repair (DDR) genes is informing clinical management in common cancers. However, defining the rare disease- associated variants in prostate cancer (PrCa) is challenging due to their low frequency. Here, whole-genome and -exome sequencing data from two independent, high- risk Australian and North American familial PrCa datasets were interrogated for novel, rare DDR variants. Segregating, high-risk, likely pathogenic DDR gene variants were identified and subsequently genotyped in 1,963 in iduals (700 familial and 459 sporadic PrCa cases, 482 unaffected relatives, and 322 screened controls) and association analyses performed accounting for relatedness (M QLS ). Rare variants significantly associated with PrCa risk were identified in ERCC3 (rs145201970, p=2.57×10 −4 ) and BRIP1 (rs4988345, p=0.025) in the combined datasets. A PARP2 (rs200603922, p=0.028) variant in the Australian dataset and a MUTYH (rs36053993, p=0.031) variant in the North American dataset were also associated with PrCa risk. No evidence for a younger age or higher-grade disease at diagnosis was evident in variant carriers. Here, we provide new evidence for four novel germline DDR PrCa risk variants. Defining the full spectrum of PrCa associated DDR genes is important for effective clinical screening and disease management.
Publisher: Springer Science and Business Media LLC
Date: 26-02-2015
Publisher: Elsevier BV
Date: 03-2021
Publisher: American Association for Cancer Research (AACR)
Date: 14-12-2009
DOI: 10.1158/0008-5472.CAN-09-0648
Abstract: Circadian genes are responsible for maintaining the ancient adaptation of a 24-hour circadian rhythm and influence a variety of cancer-related biological pathways, including the regulation of sex hormone levels. However, few studies have been undertaken to investigate the role of circadian genes in the development of prostate cancer, the most common cancer type among men (excluding nonmelanoma skin cancer). The current genetic association study tested the circadian gene hypothesis in relation to prostate cancer by genotyping a total of 41 tagging and amino acid–altering single nucleotide polymorphisms (SNP) in 10 circadian-related genes in a population-based case-control study of Caucasian men (n = 1,308 cases and 1,266 controls). Our results showed that at least one SNP in nine core circadian genes (rs885747 and rs2289591 in PER1 rs7602358 in PER2 rs1012477 in PER3 rs1534891 in CSNK1E rs12315175 in CRY1 rs2292912 in CRY2 rs7950226 in ARNTL rs11133373 in CLOCK and rs1369481, rs895521, and rs17024926 in NPAS2) was significantly associated with susceptibility to prostate cancer (either overall risk or risk of aggressive disease), and the risk estimate for four SNPs in three genes (rs885747 and rs2289591 in PER1, rs1012477 in PER3, and rs11133373 in CLOCK) varied by disease aggressiveness. Further analyses of haplotypes were consistent with these genotyping results. Findings from this candidate gene association study support the hypothesis of a link between genetic variants in circadian genes and prostate cancer risk, warranting further confirmation and mechanistic investigation of circadian biomarkers in prostate tumorigenesis. [Cancer Res 2009 (24):9315–22]
Publisher: American Association for Cancer Research (AACR)
Date: 30-04-2009
DOI: 10.1158/1078-0432.CCR-08-2190
Abstract: Purpose: Two recent genome-wide association studies have highlighted several single nucleotide polymorphisms (SNPs) purported to be associated with prostate cancer risk. We investigated the significance of these SNPs in a population-based study of Caucasian men, testing the effects of each SNP in relation to family history of prostate cancer and the clinicopathologic features of the disease. Experimental Design: We genotyped 13 SNPs in 1,308 prostate cancer patients and 1,267 unaffected controls frequency matched to cases by five-year age groups. The association of each SNP with disease risk stratified by family history of prostate cancer and clinicopathologic features of the disease was calculated with the use of logistic and polytomous regression. Results: These results confirm the importance of multiple, previously reported SNPs in relation to prostate cancer susceptibility 11 of the 13 SNPs were significantly associated with risk of developing prostate cancer. However, none of the SNP associations were of comparable magnitude with that associated with having a first-degree family history of the disease. Risk estimates associated with SNPs rs4242382 and rs2735839 varied by family history, whereas risk estimates for rs10993994 and rs5945619 varied by Gleason score. Conclusions: Our results confirm that several recently identified SNPs are associated with prostate cancer risk however, the variant alleles only confer a low to moderate relative risk of disease and are generally not associated with more aggressive disease features.
Publisher: Proceedings of the National Academy of Sciences
Date: 15-01-2002
Abstract: The known susceptibility genes for breast cancer, including BRCA1 and BRCA2, only account for a minority of the familial aggregation of the disease. A recent study of 77 multiple case breast cancer families from Scandinavia found evidence of linkage between the disease and polymorphic markers on chromosome 13q21. We have evaluated the contribution of this candidate “BRCA3” locus to breast cancer susceptibility in 128 high-risk breast cancer families of Western European ancestry with no identified BRCA1 or BRCA2 mutations. No evidence of linkage was found. The estimated proportion (α) of families linked to a susceptibility locus at D13S1308, the location estimated by Kainu et al. [(2000) Proc. Natl. Acad. Sci. USA 97, 9603–9608], was 0 (upper 95% confidence limit 0.13). Adjustment for possible bias due to selection of families on the basis of linkage evidence at BRCA2 did not materially alter this result (α = 0, upper 95% confidence limit 0.18). The proportion of linked families reported by Kainu et al. (0.65) is excluded with a high degree of confidence in our dataset [heterogeneity logarithm of odds (HLOD) at α = 0.65 was −11.0]. We conclude that, if a susceptibility gene does exist at this locus, it can only account for a small proportion of non-BRCA1/2 families with multiple cases of early-onset breast cancer.
Publisher: Springer Science and Business Media LLC
Date: 12-10-2012
Publisher: Springer Science and Business Media LLC
Date: 02-09-2008
DOI: 10.1038/PCAN.2008.46
Publisher: Hindawi Limited
Date: 04-10-2012
DOI: 10.1002/HUMU.22176
Publisher: Springer Science and Business Media LLC
Date: 11-06-2018
Publisher: Springer Science and Business Media LLC
Date: 15-08-2023
DOI: 10.1186/S13059-023-03023-7
Abstract: The international Dog10K project aims to sequence and analyze several thousand canine genomes. Incorporating 20 × data from 1987 in iduals, including 1611 dogs (321 breeds), 309 village dogs, 63 wolves, and four coyotes, we identify genomic variation across the canid family, setting the stage for detailed studies of domestication, behavior, morphology, disease susceptibility, and genome architecture and function. We report the analysis of 48 M single-nucleotide, indel, and structural variants spanning the autosomes, X chromosome, and mitochondria. We discover more than 75% of variation for 239 s led breeds. Allele sharing analysis indicates that 94.9% of breeds form monophyletic clusters and 25 major clades. German Shepherd Dogs and related breeds show the highest allele sharing with independent breeds from multiple clades. On average, each breed dog differs from the UU_Cfam_GSD_1.0 reference at 26,960 deletions and 14,034 insertions greater than 50 bp, with wolves having 14% more variants. Discovered variants include retrogene insertions from 926 parent genes. To aid functional prioritization, single-nucleotide variants were annotated with SnpEff and Zoonomia phyloP constraint scores. Constrained positions were negatively correlated with allele frequency. Finally, the utility of the Dog10K data as an imputation reference panel is assessed, generating high-confidence calls across varied genotyping platform densities including for breeds not included in the Dog10K collection. We have developed a dense dataset of 1987 sequenced canids that reveals patterns of allele sharing, identifies likely functional variants, informs breed structure, and enables accurate imputation. Dog10K data are publicly available.
Publisher: Springer Science and Business Media LLC
Date: 18-07-2021
Publisher: Oxford University Press (OUP)
Date: 27-02-2013
DOI: 10.1093/HMG/DDT095
Abstract: Parkinson's disease (PD) is a common neurodegenerative disorder characterized by selective dopaminergic cell loss in the substantia nigra, but its pathogenesis remains unclear. The recessively inherited familial PD genes PARK2 and PARK6 have been attributed to mutations in the Parkin and PTEN-induced kinase 1 (PINK1) genes, respectively. Recent reports suggest that PINK1 works upstream of Parkin in the same pathway to regulate mitochondrial dynamics and/or conduct autophagic clearance of damaged mitochondria. This phenomenon is preserved from Drosophila to human cell lines but has not been demonstrated in a vertebrate animal model in vivo. Here, we developed a medaka fish (Oryzias latipes) model that is deficient in Pink1 and Parkin. We found that despite the lack of a conspicuous phenotype in single mutants for Pink1 or Parkin, medaka that are deficient in both genes developed phenotypes similar to that of human PD: late-onset locomotor dysfunction, a decrease in dopamine levels and a selective degeneration of dopaminergic neurons. Further analysis also revealed defects in mitochondrial enzymatic activity as well as cell death. Consistently, PINK1 and Parkin double-deficient MEF showed a further decrease in mitochondrial membrane potential and mitochondrial complex I activity as well as apoptosis compared with single-deficient MEF. Interestingly, these mitochondrial abnormalities in Parkin-deficient MEF were compensated by exogenous PINK1, but not by disease-related mutants. These results suggest that PINK1 and Parkin work in a complementary way to protect dopaminergic neurons by maintaining mitochondrial function in vertebrates.
Publisher: American Association for Cancer Research (AACR)
Date: 15-05-2011
DOI: 10.1158/0008-5472.CAN-11-0314
Abstract: Compelling evidence supports a genetic component to prostate cancer susceptibility and aggressiveness. Recent genome-wide association studies have identified more than 30 single-nucleotide polymorphisms associated with prostate cancer susceptibility. It remains unclear, however, whether such genetic variants are associated with disease aggressiveness—one of the most important questions in prostate cancer research today. To help clarify this and substantially expand research in the genetic determinants of prostate cancer aggressiveness, the first National Cancer Institute Prostate Cancer Genetics Workshop assembled researchers to develop plans for a large new research consortium and patient cohort. The workshop reviewed the prior work in this area and addressed the practical issues in planning future studies. With new DNA sequencing technology, the potential application of sequencing information to patient care is emerging. The workshop, therefore, included state-of-the-art presentations by experts on new genotyping technologies, including sequencing and associated bioinformatics issues, which are just beginning to be applied to cancer genetics. Cancer Res 71(10) 3442–6. ©2011 AACR.
Publisher: Springer Science and Business Media LLC
Date: 11-06-2018
DOI: 10.1038/S41467-018-04109-8
Abstract: Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling.
Publisher: Elsevier BV
Date: 05-2009
Publisher: Wiley
Date: 17-06-2016
DOI: 10.1002/GEPI.21983
Publisher: Proceedings of the National Academy of Sciences
Date: 16-01-2003
Abstract: The role of missense changes in BRCA1 in breast cancer susceptibility has been difficult to establish. We used comparative evolutionary methods to identify potential functionally important amino acid sites in exon 11 and missense changes likely to disrupt gene function, aligning sequences from 57 eutherian mammals and categorizing amino acid sites by degree of conservation. We used Bayesian phylogenetic analyses to determine relationships among orthologs and identify codons evolving under positive selection. Most conserved residues occur in a region with the highest concentration of protein-interacting domains. Rapidly evolving residues are concentrated in the RAD51-interacting domain, suggesting that selection is acting most strongly on the role of BRCA1 in DNA repair. Investigation of the functional role of missense changes in breast-cancer susceptibility should focus on 38 missense changes in conserved and 3 in rapidly evolving regions of exon 11.
Publisher: Elsevier BV
Date: 10-2016
Publisher: Springer Science and Business Media LLC
Date: 10-07-2011
DOI: 10.1038/NG.882
Publisher: Wiley
Date: 16-02-2017
DOI: 10.1002/GEPI.22036
Publisher: Oxford University Press (OUP)
Date: 05-08-2010
DOI: 10.1093/AJE/KWQ175
Publisher: Oxford University Press (OUP)
Date: 08-2020
DOI: 10.1534/GENETICS.120.303428
Abstract: Spontaneous cancer regression in humans is uncommon, but understanding the mechanisms is key for advancing treatment. Using Devil Facial Tumor Disease as a model, Margres et al. employed comparative....
Publisher: Springer Science and Business Media LLC
Date: 25-12-2011
Publisher: Wiley
Date: 07-07-2021
DOI: 10.1111/MEC.16048
Abstract: The red wolf ( Canis rufus ) of the eastern US was driven to near‐extinction by colonial‐era persecution and habitat conversion, which facilitated coyote ( C . latrans ) range expansion and widespread hybridization with red wolves. The observation of some grey wolf ( C . lupus ) ancestry within red wolves sparked controversy over whether it was historically a subspecies of grey wolf with its predominant “coyote‐like” ancestry obtained from post‐colonial coyote hybridization (2‐species hypothesis) versus a distinct species closely related to the coyote that hybridized with grey wolf (3‐species hypothesis). We analysed mitogenomes sourced from before the 20th century bottleneck and coyote invasion, along with hundreds of modern licons, which led us to reject the 2‐species model and to investigate a broader phylogeographic 3‐species model suggested by the fossil record. Our findings broadly support this model, in which red wolves ranged the width of the American continent prior to arrival of the grey wolf to the mid‐continent 60–80 ka red wolves subsequently disappeared from the mid‐continent, relegated to California and the eastern forests, which ushered in emergence of the coyote in their place (50–30 ka) by the early Holocene (12–10 ka), coyotes had expanded into California, where they admixed with and phenotypically replaced western red wolves in a process analogous to the 20th century coyote invasion of the eastern forests. Findings indicate that the red wolf pre‐dated not only European colonization but human, and possibly coyote, presence in North America. These findings highlight the urgency of expanding conservation efforts for the red wolf.
Publisher: Springer Science and Business Media LLC
Date: 26-10-2013
Publisher: Oxford University Press (OUP)
Date: 27-02-2009
DOI: 10.1093/HMG/DDP100
Publisher: Springer Science and Business Media LLC
Date: 11-08-2008
Abstract: The presence of the TMPRSS2-ERG fusion gene in prostate tumors has recently been associated with an aggressive phenotype, as well as recurrence and death from prostate cancer. These associations suggest the hypothesis that the gene fusion may be used as a prognostic indicator for prostate cancer. In this study, fluorescent in situ hybridization (FISH) assays were used to assess TMPRSS2-ERG fusion status in a group of 214 prostate cancer cases from two population-based studies. The FISH assays were designed to detect both fusion type (deletion vs. translocation) and the number of fusion copies (single vs. multiple). Genotyping of four ERG and one TMPRSS2 SNPs using germline DNA was also performed in a s le of the cases (n = 127). Of the 214 tumors scored for the TMPRSS2-ERG fusion, 64.5% were negative and 35.5% were positive for the fusion. Cases with the TMPRSS2-ERG fusion did not exhibit reduced prostate cancer survival (HR = 0.92, 95% CI = 0.22–3.93), nor was there a significant difference in cause-specific survival when stratifying by translocation or deletion (HR = 0.84, 95% CI = 0.23–3.12) or by the number of retained fusion copies (HR = 1.22, 95% CI = 0.45–3.34). However, evidence for reduced prostate cancer-specific survival was apparent in those cases whose tumor had multiple copies of the fusion. The variant T allele of the TMPRSS2 SNP, rs12329760, was positively associated with TMPRSS2-ERG fusion by translocation (p = 0.05) and with multiple copies of the gene fusion (p = 0.03). If replicated, the results presented here may provide insight into the mechanism by which the TMPRSS2-ERG gene fusion arises and also contribute to diagnostic evaluations for determining the subset of men who will go on to develop metastatic prostate cancer.
Publisher: Wiley
Date: 03-2009
DOI: 10.1002/PROS.20887
Publisher: Springer Science and Business Media LLC
Date: 12-2005
DOI: 10.1038/NATURE04338
Abstract: Here we report a high-quality draft genome sequence of the domestic dog (Canis familiaris), together with a dense map of single nucleotide polymorphisms (SNPs) across breeds. The dog is of particular interest because it provides important evolutionary information and because existing breeds show great phenotypic ersity for morphological, physiological and behavioural traits. We use sequence comparison with the primate and rodent lineages to shed light on the structure and evolution of genomes and genes. Notably, the majority of the most highly conserved non-coding sequences in mammalian genomes are clustered near a small subset of genes with important roles in development. Analysis of SNPs reveals long-range haplotypes across the entire dog genome, and defines the nature of genetic ersity within and across breeds. The current SNP map now makes it possible for genome-wide association studies to identify genes responsible for diseases and traits, with important consequences for human and companion animal health.
Publisher: American Association for Cancer Research (AACR)
Date: 06-2011
DOI: 10.1158/1055-9965.EPI-10-1299
Abstract: Background: Of the 200,000 U.S. men annually diagnosed with prostate cancer, approximately 20% to 30% will have clinically aggressive disease. Although factors such as Gleason score and tumor stage are used to assess prognosis, there are no biomarkers to identify men at greater risk for developing aggressive prostate cancer. We therefore undertook a search for genetic variants associated with risk of more aggressive disease. Methods: A genome-wide scan was conducted in 202 prostate cancer cases with a more aggressive phenotype and 100 randomly s led, age-matched prostate-specific antigen screened negative controls. Analysis of 387,384 autosomal single nucleotide polymorphisms (SNPs) was followed by validation testing in an independent set of 527 cases with more aggressive and 595 cases with less aggressive prostate cancer, and 1,167 age-matched controls. Results: A variant on 15q13, rs6497287, was confirmed to be most strongly associated with more aggressive (Pdiscovery = 5.20 × 10−5, Pvalidation = 0.004) than less aggressive disease (P = 0.14). Another SNP on 3q26, rs3774315, was found to be associated with prostate cancer risk however, the association was not stronger for more aggressive disease. Conclusions: This study provides suggestive evidence for a genetic predisposition to more aggressive prostate cancer and highlights the fact that larger studies are warranted to confirm this supposition and identify further risk variants. Impact: These findings raise the possibility that assessment of genetic variation may one day be useful to discern men at higher risk for developing clinically significant prostate cancer. Cancer Epidemiol Biomarkers Prev 20(6) 1196–203. ©2011 AACR.
Publisher: Springer Science and Business Media LLC
Date: 04-03-2004
Publisher: Springer Science and Business Media LLC
Date: 2021
Location: United States of America
Location: United States of America
No related grants have been discovered for Elaine Ostrander.