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1.
Nat Commun ; 12(1): 1078, 2021 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-33597508

RESUMO

Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P < 10-8, at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers.


Assuntos
Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias da Mama/genética , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla/métodos , Polimorfismo de Nucleotídeo Único , Adulto , Alelos , Feminino , Genótipo , Humanos , Desequilíbrio de Ligação , Pessoa de Meia-Idade , Mutação , Locos de Características Quantitativas/genética , Fatores de Risco
2.
Nat Genet ; 52(1): 56-73, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31911677

RESUMO

Genome-wide association studies have identified breast cancer risk variants in over 150 genomic regions, but the mechanisms underlying risk remain largely unknown. These regions were explored by combining association analysis with in silico genomic feature annotations. We defined 205 independent risk-associated signals with the set of credible causal variants in each one. In parallel, we used a Bayesian approach (PAINTOR) that combines genetic association, linkage disequilibrium and enriched genomic features to determine variants with high posterior probabilities of being causal. Potentially causal variants were significantly over-represented in active gene regulatory regions and transcription factor binding sites. We applied our INQUSIT pipeline for prioritizing genes as targets of those potentially causal variants, using gene expression (expression quantitative trait loci), chromatin interaction and functional annotations. Known cancer drivers, transcription factors and genes in the developmental, apoptosis, immune system and DNA integrity checkpoint gene ontology pathways were over-represented among the highest-confidence target genes.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Mapeamento Cromossômico/métodos , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas , Teorema de Bayes , Feminino , Humanos , Desequilíbrio de Ligação , Sequências Reguladoras de Ácido Nucleico , Fatores de Risco
3.
Am J Hum Genet ; 104(1): 21-34, 2019 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-30554720

RESUMO

Stratification of women according to their risk of breast cancer based on polygenic risk scores (PRSs) could improve screening and prevention strategies. Our aim was to develop PRSs, optimized for prediction of estrogen receptor (ER)-specific disease, from the largest available genome-wide association dataset and to empirically validate the PRSs in prospective studies. The development dataset comprised 94,075 case subjects and 75,017 control subjects of European ancestry from 69 studies, divided into training and validation sets. Samples were genotyped using genome-wide arrays, and single-nucleotide polymorphisms (SNPs) were selected by stepwise regression or lasso penalized regression. The best performing PRSs were validated in an independent test set comprising 11,428 case subjects and 18,323 control subjects from 10 prospective studies and 190,040 women from UK Biobank (3,215 incident breast cancers). For the best PRSs (313 SNPs), the odds ratio for overall disease per 1 standard deviation in ten prospective studies was 1.61 (95%CI: 1.57-1.65) with area under receiver-operator curve (AUC) = 0.630 (95%CI: 0.628-0.651). The lifetime risk of overall breast cancer in the top centile of the PRSs was 32.6%. Compared with women in the middle quintile, those in the highest 1% of risk had 4.37- and 2.78-fold risks, and those in the lowest 1% of risk had 0.16- and 0.27-fold risks, of developing ER-positive and ER-negative disease, respectively. Goodness-of-fit tests indicated that this PRS was well calibrated and predicts disease risk accurately in the tails of the distribution. This PRS is a powerful and reliable predictor of breast cancer risk that may improve breast cancer prevention programs.


Assuntos
Neoplasias da Mama/classificação , Neoplasias da Mama/genética , Predisposição Genética para Doença , Herança Multifatorial/genética , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/prevenção & controle , Feminino , Humanos , Anamnese , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Receptores Estrogênicos/metabolismo , Reprodutibilidade dos Testes , Medição de Risco
4.
Int J Epidemiol ; 46(6): 1814-1822, 2017 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-29232439

RESUMO

Background: There is increasing evidence that elevated body mass index (BMI) is associated with reduced survival for women with breast cancer. However, the underlying reasons remain unclear. We conducted a Mendelian randomization analysis to investigate a possible causal role of BMI in survival from breast cancer. Methods: We used individual-level data from six large breast cancer case-cohorts including a total of 36 210 individuals (2475 events) of European ancestry. We created a BMI genetic risk score (GRS) based on genotypes at 94 known BMI-associated genetic variants. Association between the BMI genetic score and breast cancer survival was analysed by Cox regression for each study separately. Study-specific hazard ratios were pooled using fixed-effect meta-analysis. Results: BMI genetic score was found to be associated with reduced breast cancer-specific survival for estrogen receptor (ER)-positive cases [hazard ratio (HR) = 1.11, per one-unit increment of GRS, 95% confidence interval (CI) 1.01-1.22, P = 0.03). We observed no association for ER-negative cases (HR = 1.00, per one-unit increment of GRS, 95% CI 0.89-1.13, P = 0.95). Conclusions: Our findings suggest a causal effect of increased BMI on reduced breast cancer survival for ER-positive breast cancer. There is no evidence of a causal effect of higher BMI on survival for ER-negative breast cancer cases.


Assuntos
Índice de Massa Corporal , Neoplasias da Mama/genética , Neoplasias da Mama/mortalidade , Grupo com Ancestrais do Continente Europeu/estatística & dados numéricos , Receptores Estrogênicos/genética , Causalidade , Europa (Continente)/epidemiologia , Feminino , Variação Genética , Humanos , Análise da Randomização Mendeliana , Metanálise como Assunto , Polimorfismo de Nucleotídeo Único , Medição de Risco , Fatores de Risco , Análise de Sobrevida
5.
Oncotarget ; 8(61): 102769-102782, 2017 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-29262523

RESUMO

Most non-BRCA1/2 breast cancer families have no identified genetic cause. We used linkage and haplotype analyses in familial and sporadic breast cancer cases to identify a susceptibility locus on chromosome 6q. Two independent genome-wide linkage analysis studies suggested a 3 Mb locus on chromosome 6q and two unrelated Swedish families with a LOD >2 together seemed to share a haplotype in 6q14.1. We hypothesized that this region harbored a rare high-risk founder allele contributing to breast cancer in these two families. Sequencing of DNA and RNA from the two families did not detect any pathogenic mutations. Finally, 29 SNPs in the region were analyzed in 44,214 cases and 43,532 controls from BCAC, and the original haplotypes in the two families were suggested as low-risk alleles for European and Swedish women specifically. There was also some support for one additional independent moderate-risk allele in Swedish familial samples. The results were consistent with our previous findings in familial breast cancer and supported a breast cancer susceptibility locus at 6q14.1 around the PHIP gene.

6.
Oncotarget ; 8(11): 18381-18398, 2017 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-28179588

RESUMO

TP53 overexpression is indicative of somatic TP53 mutations and associates with aggressive tumors and poor prognosis in breast cancer. We utilized a two-stage SNP association study to detect variants associated with breast cancer survival in a TP53-dependent manner. Initially, a genome-wide study (n = 575 cases) was conducted to discover candidate SNPs for genotyping and validation in the Breast Cancer Association Consortium (BCAC). The SNPs were then tested for interaction with tumor TP53 status (n = 4,610) and anthracycline treatment (n = 17,828). For SNPs interacting with anthracycline treatment, siRNA knockdown experiments were carried out to validate candidate genes.In the test for interaction between SNP genotype and TP53 status, we identified one locus, represented by rs10916264 (p(interaction) = 3.44 × 10-5; FDR-adjusted p = 0.0011) in estrogen receptor (ER) positive cases. The rs10916264 AA genotype associated with worse survival among cases with ER-positive, TP53-positive tumors (hazard ratio [HR] 2.36, 95% confidence interval [C.I] 1.45 - 3.82). This is a cis-eQTL locus for FBXO28 and TP53BP2; expression levels of these genes were associated with patient survival specifically in ER-positive, TP53-mutated tumors. Additionally, the SNP rs798755 was associated with survival in interaction with anthracycline treatment (p(interaction) = 9.57 × 10-5, FDR-adjusted p = 0.0130). RNAi-based depletion of a predicted regulatory target gene, FAM53A, indicated that this gene can modulate doxorubicin sensitivity in breast cancer cell lines.If confirmed in independent data sets, these results may be of clinical relevance in the development of prognostic and predictive marker panels for breast cancer.


Assuntos
Antraciclinas/uso terapêutico , Neoplasias da Mama/genética , Locos de Características Quantitativas , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteínas Reguladoras de Apoptose/genética , Neoplasias da Mama/patologia , Feminino , Genótipo , Humanos , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Proteínas Ligases SKP Culina F-Box/genética , Análise de Sobrevida , Resultado do Tratamento , Proteína Supressora de Tumor p53/genética , Adulto Jovem
7.
Int J Cancer ; 139(6): 1303-1317, 2016 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-27087578

RESUMO

Previous genome-wide association studies among women of European ancestry identified two independent breast cancer susceptibility loci represented by single nucleotide polymorphisms (SNPs) rs13281615 and rs11780156 at 8q24. A fine-mapping study across 2.06 Mb (chr8:127,561,724-129,624,067, hg19) in 55,540 breast cancer cases and 51,168 controls within the Breast Cancer Association Consortium was conducted. Three additional independent association signals in women of European ancestry, represented by rs35961416 (OR = 0.95, 95% CI = 0.93-0.97, conditional p = 5.8 × 10(-6) ), rs7815245 (OR = 0.94, 95% CI = 0.91-0.96, conditional p = 1.1 × 10(-6) ) and rs2033101 (OR = 1.05, 95% CI = 1.02-1.07, conditional p = 1.1 × 10(-4) ) were found. Integrative analysis using functional genomic data from the Roadmap Epigenomics, the Encyclopedia of DNA Elements project, the Cancer Genome Atlas and other public resources implied that SNPs rs7815245 in Signal 3, and rs1121948 in Signal 5 (in linkage disequilibrium with rs11780156, r(2) = 0.77), were putatively functional variants for two of the five independent association signals. The results highlighted multiple 8q24 variants associated with breast cancer susceptibility in women of European ancestry.


Assuntos
Neoplasias da Mama/epidemiologia , Neoplasias da Mama/genética , Mapeamento Cromossômico , Cromossomos Humanos Par 8/genética , Variação Genética , Locos de Características Quantitativas , Alelos , Estudos de Casos e Controles , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Estudo de Associação Genômica Ampla , Genótipo , Haplótipos , Humanos , Desequilíbrio de Ligação , Razão de Chances , Polimorfismo de Nucleotídeo Único , Risco
8.
BMC Bioinformatics ; 16: 53, 2015 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-25888290

RESUMO

BACKGROUND: The detection of bias due to cryptic population structure is an important step in the evaluation of findings of genetic association studies. The standard method of measuring this bias in a genetic association study is to compare the observed median association test statistic to the expected median test statistic. This ratio is inflated in the presence of cryptic population structure. However, inflation may also be caused by the properties of the association test itself particularly in the analysis of rare variants. We compared the properties of the three most commonly used association tests: the likelihood ratio test, the Wald test and the score test when testing rare variants for association using simulated data. RESULTS: We found evidence of inflation in the median test statistics of the likelihood ratio and score tests for tests of variants with less than 20 heterozygotes across the sample, regardless of the total sample size. The test statistics for the Wald test were under-inflated at the median for variants below the same minor allele frequency. CONCLUSIONS: In a genetic association study, if a substantial proportion of the genetic variants tested have rare minor allele frequencies, the properties of the association test may mask the presence or absence of bias due to population structure. The use of either the likelihood ratio test or the score test is likely to lead to inflation in the median test statistic in the absence of population structure. In contrast, the use of the Wald test is likely to result in under-inflation of the median test statistic which may mask the presence of population structure.


Assuntos
Interpretação Estatística de Dados , Variação Genética/genética , Modelos Genéticos , Modelos Estatísticos , Estudos de Casos e Controles , Simulação por Computador , Frequência do Gene , Estudos de Associação Genética , Marcadores Genéticos , Predisposição Genética para Doença , Heterozigoto , Humanos
9.
J Natl Cancer Inst ; 107(5)2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25890600

RESUMO

BACKGROUND: Survival after a diagnosis of breast cancer varies considerably between patients, and some of this variation may be because of germline genetic variation. We aimed to identify genetic markers associated with breast cancer-specific survival. METHODS: We conducted a large meta-analysis of studies in populations of European ancestry, including 37954 patients with 2900 deaths from breast cancer. Each study had been genotyped for between 200000 and 900000 single nucleotide polymorphisms (SNPs) across the genome; genotypes for nine million common variants were imputed using a common reference panel from the 1000 Genomes Project. We also carried out subtype-specific analyses based on 6881 estrogen receptor (ER)-negative patients (920 events) and 23059 ER-positive patients (1333 events). All statistical tests were two-sided. RESULTS: We identified one new locus (rs2059614 at 11q24.2) associated with survival in ER-negative breast cancer cases (hazard ratio [HR] = 1.95, 95% confidence interval [CI] = 1.55 to 2.47, P = 1.91 x 10(-8)). Genotyping a subset of 2113 case patients, of which 300 were ER negative, provided supporting evidence for the quality of the imputation. The association in this set of case patients was stronger for the observed genotypes than for the imputed genotypes. A second locus (rs148760487 at 2q24.2) was associated at genome-wide statistical significance in initial analyses; the association was similar in ER-positive and ER-negative case patients. Here the results of genotyping suggested that the finding was less robust. CONCLUSIONS: This is currently the largest study investigating genetic variation associated with breast cancer survival. Our results have potential clinical implications, as they confirm that germline genotype can provide prognostic information in addition to standard tumor prognostic factors.


Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/mortalidade , Polimorfismo de Nucleotídeo Único , Neoplasias da Mama/química , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Marcadores Genéticos , Predisposição Genética para Doença , Genótipo , Humanos , Prognóstico , Receptores Estrogênicos/análise , Análise de Sobrevida
10.
Breast Cancer Res ; 17: 58, 2015 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-25897948

RESUMO

INTRODUCTION: Previous studies have identified common germline variants nominally associated with breast cancer survival. These associations have not been widely replicated in further studies. The purpose of this study was to evaluate the association of previously reported SNPs with breast cancer-specific survival using data from a pooled analysis of eight breast cancer survival genome-wide association studies (GWAS) from the Breast Cancer Association Consortium. METHODS: A literature review was conducted of all previously published associations between common germline variants and three survival outcomes: breast cancer-specific survival, overall survival and disease-free survival. All associations that reached the nominal significance level of P value <0.05 were included. Single nucleotide polymorphisms that had been previously reported as nominally associated with at least one survival outcome were evaluated in the pooled analysis of over 37,000 breast cancer cases for association with breast cancer-specific survival. Previous associations were evaluated using a one-sided test based on the reported direction of effect. RESULTS: Fifty-six variants from 45 previous publications were evaluated in the meta-analysis. Fifty-four of these were evaluated in the full set of 37,954 breast cancer cases with 2,900 events and the two additional variants were evaluated in a reduced sample size of 30,000 samples in order to ensure independence from the previously published studies. Five variants reached nominal significance (P <0.05) in the pooled GWAS data compared to 2.8 expected under the null hypothesis. Seven additional variants were associated (P <0.05) with ER-positive disease. CONCLUSIONS: Although no variants reached genome-wide significance (P <5 x 10(-8)), these results suggest that there is some evidence of association between candidate common germline variants and breast cancer prognosis. Larger studies from multinational collaborations are necessary to increase the power to detect associations, between common variants and prognosis, at more stringent significance levels.


Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/mortalidade , Células Germinativas/metabolismo , Polimorfismo de Nucleotídeo Único , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Prognóstico
11.
Nat Genet ; 47(4): 373-80, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25751625

RESUMO

Genome-wide association studies (GWAS) and large-scale replication studies have identified common variants in 79 loci associated with breast cancer, explaining ∼14% of the familial risk of the disease. To identify new susceptibility loci, we performed a meta-analysis of 11 GWAS, comprising 15,748 breast cancer cases and 18,084 controls together with 46,785 cases and 42,892 controls from 41 studies genotyped on a 211,155-marker custom array (iCOGS). Analyses were restricted to women of European ancestry. We generated genotypes for more than 11 million SNPs by imputation using the 1000 Genomes Project reference panel, and we identified 15 new loci associated with breast cancer at P < 5 × 10(-8). Combining association analysis with ChIP-seq chromatin binding data in mammary cell lines and ChIA-PET chromatin interaction data from ENCODE, we identified likely target genes in two regions: SETBP1 at 18q12.3 and RNF115 and PDZK1 at 1q21.1. One association appears to be driven by an amino acid substitution encoded in EXO1.


Assuntos
Neoplasias da Mama/genética , Loci Gênicos , Predisposição Genética para Doença , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Estudo de Associação Genômica Ampla , Humanos , Metanálise como Assunto , Análise em Microsséries , Polimorfismo de Nucleotídeo Único
12.
Nat Genet ; 45(4): 371-84, 384e1-2, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23535731

RESUMO

TERT-locus SNPs and leukocyte telomere measures are reportedly associated with risks of multiple cancers. Using the Illumina custom genotyping array iCOGs, we analyzed ∼480 SNPs at the TERT locus in breast (n = 103,991), ovarian (n = 39,774) and BRCA1 mutation carrier (n = 11,705) cancer cases and controls. Leukocyte telomere measurements were also available for 53,724 participants. Most associations cluster into three independent peaks. The minor allele at the peak 1 SNP rs2736108 associates with longer telomeres (P = 5.8 × 10(-7)), lower risks for estrogen receptor (ER)-negative (P = 1.0 × 10(-8)) and BRCA1 mutation carrier (P = 1.1 × 10(-5)) breast cancers and altered promoter assay signal. The minor allele at the peak 2 SNP rs7705526 associates with longer telomeres (P = 2.3 × 10(-14)), higher risk of low-malignant-potential ovarian cancer (P = 1.3 × 10(-15)) and greater promoter activity. The minor alleles at the peak 3 SNPs rs10069690 and rs2242652 increase ER-negative (P = 1.2 × 10(-12)) and BRCA1 mutation carrier (P = 1.6 × 10(-14)) breast and invasive ovarian (P = 1.3 × 10(-11)) cancer risks but not via altered telomere length. The cancer risk alleles of rs2242652 and rs10069690, respectively, increase silencing and generate a truncated TERT splice variant.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/etiologia , Loci Gênicos/genética , Neoplasias Ovarianas/etiologia , Polimorfismo de Nucleotídeo Único/genética , Telomerase/genética , Telômero/genética , Processamento Alternativo , Neoplasias da Mama/patologia , Estudos de Casos e Controles , Cromatina/genética , Metilação de DNA , Feminino , Perfilação da Expressão Gênica , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Luciferases/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , Neoplasias Ovarianas/patologia , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Risco
13.
Database (Oxford) ; 2011: bar041, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21930507

RESUMO

BioMart Central Portal is a first of its kind, community-driven effort to provide unified access to dozens of biological databases spanning genomics, proteomics, model organisms, cancer data, ontology information and more. Anybody can contribute an independently maintained resource to the Central Portal, allowing it to be exposed to and shared with the research community, and linking it with the other resources in the portal. Users can take advantage of the common interface to quickly utilize different sources without learning a new system for each. The system also simplifies cross-database searches that might otherwise require several complicated steps. Several integrated tools streamline common tasks, such as converting between ID formats and retrieving sequences. The combination of a wide variety of databases, an easy-to-use interface, robust programmatic access and the array of tools make Central Portal a one-stop shop for biological data querying. Here, we describe the structure of Central Portal and show example queries to demonstrate its capabilities.


Assuntos
Pesquisa Biomédica , Sistemas de Gerenciamento de Base de Dados , Bases de Dados Factuais , Internet , Animais , Bactérias , Fungos , Genoma , Humanos , Cooperação Internacional , Interface Usuário-Computador , Vírus
14.
Nucleic Acids Res ; 39(Database issue): D514-9, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20929869

RESUMO

The HUGO Gene Nomenclature Committee (HGNC) aims to assign a unique gene symbol and name to every human gene. The HGNC database currently contains almost 30,000 approved gene symbols, over 19,000 of which represent protein-coding genes. The public website, www.genenames.org, displays all approved nomenclature within Symbol Reports that contain data curated by HGNC editors and links to related genomic, phenotypic and proteomic information. Here we describe improvements to our resources, including a new Quick Gene Search, a new List Search, an integrated HGNC BioMart and a new Statistics and Downloads facility.


Assuntos
Bases de Dados Genéticas , Genes , Terminologia como Assunto , Animais , Genômica , Humanos , Fenótipo , Proteômica , Software
15.
Nucleic Acids Res ; 36(Database issue): D445-8, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17984084

RESUMO

The HUGO Gene Nomenclature Committee (HGNC) aims to assign a unique and ideally meaningful name and symbol to every human gene. The HGNC database currently comprises over 24 000 public records containing approved human gene nomenclature and associated gene information. Following our recent relocation to the European Bioinformatics Institute our homepage can now be found at http://www.genenames.org, with direct links to the searchable HGNC database and other related database resources, such as the HCOP orthology search tool and manually curated gene family webpages.


Assuntos
Bases de Dados Genéticas , Genoma Humano , Terminologia como Assunto , Animais , Genes , Variação Genética , Genômica , Humanos , Internet , Camundongos , Integração de Sistemas , Interface Usuário-Computador
16.
Brief Bioinform ; 8(1): 2-5, 2007 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16951416

RESUMO

The HUGO Gene Nomenclature Committee (HGNC) Comparison of Orthology Predictions (HCOP) search tool combines the human, mouse, rat and chicken orthology assertions made by PhIGs, HomoloGene, Ensembl, Inparanoid, Mouse Genome Informatics (MGI) and HGNC, enabling users to identify predicted ortholog pairs for a specified gene or genes. The HCOP resource provides a useful method to integrate, compare and access a variety of disparate sources of human orthology data. The HCOP search tool, data and documentation are available at http://www.gene.ucl.ac.uk/hcop.


Assuntos
Bases de Dados Genéticas , Evolução Molecular , Genômica/métodos , Genes , Humanos , Homologia de Sequência do Ácido Nucleico , Terminologia como Assunto
17.
Nucleic Acids Res ; 34(Database issue): D319-21, 2006 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-16381876

RESUMO

The HUGO Gene Nomenclature Committee (HGNC) aims to give every human gene a unique and ideally meaningful name and symbol. The HGNC database, previously known as Genew, contains over 22,000 public records with approved human gene nomenclature and associated information. The database has undergone major improvements throughout the last year, is publicly available for online searching at http://www.gene.ucl.ac.uk/cgi-bin/nomenclature/searchgenes.pl and has a new custom downloads interface at http://www.gene.ucl.ac.uk/cgi-bin/nomenclature/gdlw.pl.


Assuntos
Bases de Dados Genéticas , Genes , Terminologia como Assunto , Humanos , Internet , Interface Usuário-Computador
18.
Mamm Genome ; 16(11): 827-8, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16284797

RESUMO

The HGNC Comparison of Orthology Predictions search tool, HCOP (http://www.gene.ucl.ac.uk/cgi-bin/nomenclature/hcop.pl ), enables users to compare predicted human and mouse orthologs for a specified gene, or set of genes, from either species according to the ortholog assertions from the Ensembl, HGNC, Homologene, Inparanoid, MGI and PhIGs databases. Users can assess the reliability of the prediction from the number of these different sources that identify a particular orthologous pair. HCOP provides a useful one-stop resource to summarise, compare and access various sources of human and mouse orthology data.


Assuntos
Bases de Dados Genéticas , Evolução Molecular , Genes , Genômica/métodos , Animais , Bases de Dados Genéticas/normas , Genoma , Humanos , Camundongos
19.
Nat Rev Genet ; 5(12): 889-99, 2004 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-15573121

RESUMO

The major histocompatibility complex (MHC) is the most important region in the vertebrate genome with respect to infection and autoimmunity, and is crucial in adaptive and innate immunity. Decades of biomedical research have revealed many MHC genes that are duplicated, polymorphic and associated with more diseases than any other region of the human genome. The recent completion of several large-scale studies offers the opportunity to assimilate the latest data into an integrated gene map of the extended human MHC. Here, we present this map and review its content in relation to paralogy, polymorphism, immune function and disease.


Assuntos
Genoma Humano , Complexo Principal de Histocompatibilidade , Doenças Autoimunes/genética , Mapeamento Cromossômico , Cromossomos Humanos Par 6 , Humanos , Imunidade , Família Multigênica , Polimorfismo Genético , RNA de Transferência/genética
20.
Nucleic Acids Res ; 32(Database issue): D255-7, 2004 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-14681406

RESUMO

Genew, the Human Gene Nomenclature Database http://www.gene.ucl.ac.uk/cgi-bin/nomenclature/searchgenes.pl is the only resource that provides data for all human genes that have approved symbols. It is managed by the HUGO Gene Nomenclature Committee (HGNC) as a confidential database, containing over 22 000 records, 75% of which are represented online by a publicly searchable text file. Since 2002, there have been significant improvements to the Genew search engine. Additionally we have increased our capacity to analyse confidential sequence data, which has enabled us to manage the large numbers of gene symbol requests that we receive from the chromosome sequencing consortia.


Assuntos
Bases de Dados Genéticas , Genes , Terminologia como Assunto , Animais , Biologia Computacional , Humanos , Armazenamento e Recuperação da Informação , Internet , Interface Usuário-Computador
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