The complete BRCA2 gene and mutations in chromosome 13q-linked kindreds.


:Breast carcinoma is the most common malignancy among women in developed countries. Because family history remains the strongest single predictor of breast cancer risk, attention has focused on the role of highly penetrant, dominantly inherited genes in cancer-prone kindreds (1). BRCA1 was localized to chromosome 17 through analysis of a set of high-risk kindreds (2), and then identified four years later by a positional cloning strategy (3). BRCA2 was mapped to chromosomal 13q at about the same time (4). Just fifteen months later, Wooster et al. (5) reported a partial BRCA2 sequence and six mutations predicted to cause truncation of the BRCA2 protein. While these findings provide strong evidence that the identified gene corresponds to BRCA2, only two thirds of the coding sequence and 8 out of 27 exons were isolated and screened; consequently, several questions remained unanswered regarding the nature of BRCA2 and the frequency of mutations in 13q-linked families. We have now determined the complete coding sequence and exonic structure of BRCA2 (GenBank accession #U43746), and examined its pattern of expression. Here, we provide sequences for a set of PCR primers sufficient to screen the entire coding sequence of BRCA2 using genomic DNA. We also report a mutational analysis of BRCA2 in families selected on the basis of linkage analysis and/or the presence of one or more cases of male breast cancer. Together with the specific mutations described previously, our data provide preliminary insight into the BRCA2 mutation profile.


Nat Genet


Nature genetics


Tavtigian SV,Simard J,Rommens J,Couch F,Shattuck-Eidens D,Neuhausen S,Merajver S,Thorlacius S,Offit K,Stoppa-Lyonnet D,Belanger C,Bell R,Berry S,Bogden R,Chen Q,Davis T,Dumont M,Frye C,Hattier T,Jammulapati S,Jane




Has Abstract


1996-03-01 00:00:00












  • Small island, big genetic discoveries.

    abstract::Three new studies have identified new genes and sequence variants implicated in blood lipids, inflammatory markers, hemoglobin levels and adult height variation in Sardinia. These reports highlight the usefulness of large-scale genotype imputation based on whole-genome sequencing, particularly in isolated populations,...

    journal_title:Nature genetics

    pub_type: 杂志文章


    authors: Lettre G,Hirschhorn JN

    更新日期:2015-11-01 00:00:00

  • Identification of the gene that, when mutated, causes the human obesity syndrome BBS4.

    abstract::Bardet-Biedl syndrome (BBS, MIM 209900) is a heterogeneous autosomal recessive disorder characterized by obesity, pigmentary retinopathy, polydactyly, renal malformations, mental retardation, and hypogenitalism. The disorder is also associated with diabetes mellitus, hypertension, and congenital heart disease. Six dis...

    journal_title:Nature genetics

    pub_type: 杂志文章


    authors: Mykytyn K,Braun T,Carmi R,Haider NB,Searby CC,Shastri M,Beck G,Wright AF,Iannaccone A,Elbedour K,Riise R,Baldi A,Raas-Rothschild A,Gorman SW,Duhl DM,Jacobson SG,Casavant T,Stone EM,Sheffield VC

    更新日期:2001-06-01 00:00:00

  • Substitutions in woolly mammoth hemoglobin confer biochemical properties adaptive for cold tolerance.

    abstract::We have genetically retrieved, resurrected and performed detailed structure-function analyses on authentic woolly mammoth hemoglobin to reveal for the first time both the evolutionary origins and the structural underpinnings of a key adaptive physiochemical trait in an extinct species. Hemoglobin binds and carries O(2...

    journal_title:Nature genetics

    pub_type: 杂志文章


    authors: Campbell KL,Roberts JE,Watson LN,Stetefeld J,Sloan AM,Signore AV,Howatt JW,Tame JR,Rohland N,Shen TJ,Austin JJ,Hofreiter M,Ho C,Weber RE,Cooper A

    更新日期:2010-06-01 00:00:00

  • A genetic link between cold responses and flowering time through FVE in Arabidopsis thaliana.

    abstract::Cold induces expression of a number of genes that encode proteins that enhance tolerance to freezing temperatures in plants. A cis-acting element responsive to cold and drought, the C-repeat/dehydration-responsive element (C/DRE), was identified in the Arabidopsis thaliana stress-inducible genes RD29A and COR15a and f...

    journal_title:Nature genetics

    pub_type: 杂志文章


    authors: Kim HJ,Hyun Y,Park JY,Park MJ,Park MK,Kim MD,Kim HJ,Lee MH,Moon J,Lee I,Kim J

    更新日期:2004-02-01 00:00:00

  • SMARCB1 is required for widespread BAF complex-mediated activation of enhancers and bivalent promoters.

    abstract::Perturbations to mammalian SWI/SNF (mSWI/SNF or BAF) complexes contribute to more than 20% of human cancers, with driving roles first identified in malignant rhabdoid tumor, an aggressive pediatric cancer characterized by biallelic inactivation of the core BAF complex subunit SMARCB1 (BAF47). However, the mechanism by...

    journal_title:Nature genetics

    pub_type: 杂志文章


    authors: Nakayama RT,Pulice JL,Valencia AM,McBride MJ,McKenzie ZM,Gillespie MA,Ku WL,Teng M,Cui K,Williams RT,Cassel SH,Qing H,Widmer CJ,Demetri GD,Irizarry RA,Zhao K,Ranish JA,Kadoch C

    更新日期:2017-11-01 00:00:00

  • MASA syndrome is due to mutations in the neural cell adhesion gene L1CAM.

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    journal_title:Nature genetics

    pub_type: 杂志文章


    authors: Vits L,Van Camp G,Coucke P,Fransen E,De Boulle K,Reyniers E,Korn B,Poustka A,Wilson G,Schrander-Stumpel C

    更新日期:1994-07-01 00:00:00

  • An evolutionary framework for measuring epigenomic information and estimating cell-type-specific fitness consequences.

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    journal_title:Nature genetics

    pub_type: 杂志文章


    authors: Gulko B,Siepel A

    更新日期:2019-02-01 00:00:00

  • The gene encoding phosphodiesterase 4D confers risk of ischemic stroke.

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    journal_title:Nature genetics

    pub_type: 杂志文章


    authors: Gretarsdottir S,Thorleifsson G,Reynisdottir ST,Manolescu A,Jonsdottir S,Jonsdottir T,Gudmundsdottir T,Bjarnadottir SM,Einarsson OB,Gudjonsdottir HM,Hawkins M,Gudmundsson G,Gudmundsdottir H,Andrason H,Gudmundsdottir AS,Sigur

    更新日期:2003-10-01 00:00:00

  • Biochemical networking contributes more to genetic buffering in human and mouse metabolic pathways than does gene duplication.

    abstract::During evolution different genes evolve at unequal rates, reflecting the varying functional constraints on phenotype. An important contributor to this variation is genetic buffering, which reduces the potential detrimental effects of mutations. We studied whether gene duplication and redundant metabolic networks affec...

    journal_title:Nature genetics

    pub_type: 杂志文章


    authors: Kitami T,Nadeau JH

    更新日期:2002-09-01 00:00:00

  • Cryptic boundaries in roof plate and choroid plexus identified by intersectional gene activation.

    abstract::The hindbrain roof plate and choroid plexus are essential organizing centers for inducing dorsal neuron fates and sustaining neuron function. To map the formation of these structures, we developed a broadly applicable, high resolution, recombinase-based method for mapping the fate of cells originating from coordinates...

    journal_title:Nature genetics

    pub_type: 杂志文章


    authors: Awatramani R,Soriano P,Rodriguez C,Mai JJ,Dymecki SM

    更新日期:2003-09-01 00:00:00

  • A missense mutation in the neuronal nicotinic acetylcholine receptor alpha 4 subunit is associated with autosomal dominant nocturnal frontal lobe epilepsy.

    abstract::Epilepsy affects at least 2% of the population at some time in their lives. The epilepsies are a heterogeneous group of disorders, many with an inherited component. Although specific genes have been identified in a few rare diseases causing seizures as part of a more diffuse brain disorder, the molecular pathology of ...

    journal_title:Nature genetics

    pub_type: 杂志文章


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    更新日期:1995-10-01 00:00:00

  • Mutations in a new member of the chromodomain gene family cause CHARGE syndrome.

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    journal_title:Nature genetics

    pub_type: 杂志文章


    authors: Vissers LE,van Ravenswaaij CM,Admiraal R,Hurst JA,de Vries BB,Janssen IM,van der Vliet WA,Huys EH,de Jong PJ,Hamel BC,Schoenmakers EF,Brunner HG,Veltman JA,van Kessel AG

    更新日期:2004-09-01 00:00:00

  • Mutations in the gene encoding the lamin B receptor produce an altered nuclear morphology in granulocytes (Pelger-Huët anomaly).

    abstract::Pelger-Huët anomaly (PHA; OMIM *169400) is an autosomal dominant disorder characterized by abnormal nuclear shape and chromatin organization in blood granulocytes. Affected individuals show hypolobulated neutrophil nuclei with coarse chromatin. Presumed homozygous individuals have ovoid neutrophil nuclei, as well as v...

    journal_title:Nature genetics

    pub_type: 杂志文章


    authors: Hoffmann K,Dreger CK,Olins AL,Olins DE,Shultz LD,Lucke B,Karl H,Kaps R,Müller D,Vayá A,Aznar J,Ware RE,Sotelo Cruz N,Lindner TH,Herrmann H,Reis A,Sperling K

    更新日期:2002-08-01 00:00:00

  • Meta-analysis of three genome-wide association studies identifies susceptibility loci for colorectal cancer at 1q41, 3q26.2, 12q13.13 and 20q13.33.

    abstract::Genome-wide association studies (GWAS) have identified ten loci harboring common variants that influence risk of developing colorectal cancer (CRC). To enhance the power to identify additional CRC risk loci, we conducted a meta-analysis of three GWAS from the UK which included a total of 3,334 affected individuals (ca...

    journal_title:Nature genetics

    pub_type: 杂志文章


    authors: Houlston RS,Cheadle J,Dobbins SE,Tenesa A,Jones AM,Howarth K,Spain SL,Broderick P,Domingo E,Farrington S,Prendergast JG,Pittman AM,Theodoratou E,Smith CG,Olver B,Walther A,Barnetson RA,Churchman M,Jaeger EE,Penegar

    更新日期:2010-11-01 00:00:00

  • A bisexually reproducing all-triploid vertebrate.

    abstract::Green toads are common in the Palaearctic region, where they have differentiated into several taxa. The toads exist with variable amounts of ploidy, similar to other anuran species or reptiles. In vertebrate biology, the very rare occurrence of triploidy is coupled with infertility or unisexuality, or requires the coe...

    journal_title:Nature genetics

    pub_type: 杂志文章


    authors: Stöck M,Lamatsch DK,Steinlein C,Epplen JT,Grosse WR,Hock R,Klapperstück T,Lampert KP,Scheer U,Schmid M,Schartl M

    更新日期:2002-03-01 00:00:00

  • A detrimental mitochondrial-nuclear interaction causes cytoplasmic male sterility in rice.

    abstract::Plant cytoplasmic male sterility (CMS) results from incompatibilities between the organellar and nuclear genomes and prevents self pollination, enabling hybrid crop breeding to increase yields. The Wild Abortive CMS (CMS-WA) has been exploited in the majority of 'three-line' hybrid rice production since the 1970s, but...

    journal_title:Nature genetics

    pub_type: 杂志文章


    authors: Luo D,Xu H,Liu Z,Guo J,Li H,Chen L,Fang C,Zhang Q,Bai M,Yao N,Wu H,Wu H,Ji C,Zheng H,Chen Y,Ye S,Li X,Zhao X,Li R,Liu YG

    更新日期:2013-05-01 00:00:00

  • PTPRD (protein tyrosine phosphatase receptor type delta) is associated with restless legs syndrome.

    abstract::We identified association of restless legs syndrome (RLS) with PTPRD at 9p23-24 in 2,458 affected individuals and 4,749 controls from Germany, Austria, Czechia and Canada. Two independent SNPs in the 5' UTR of splice variants expressed predominantly in the central nervous system showed highly significant P values (rs4...

    journal_title:Nature genetics

    pub_type: 杂志文章


    authors: Schormair B,Kemlink D,Roeske D,Eckstein G,Xiong L,Lichtner P,Ripke S,Trenkwalder C,Zimprich A,Stiasny-Kolster K,Oertel W,Bachmann CG,Paulus W,Högl B,Frauscher B,Gschliesser V,Poewe W,Peglau I,Vodicka P,Vávrová J,S

    更新日期:2008-08-01 00:00:00

  • A genome-wide association study confirms PNPLA3 and identifies TM6SF2 and MBOAT7 as risk loci for alcohol-related cirrhosis.

    abstract::Alcohol misuse is the leading cause of cirrhosis and the second most common indication for liver transplantation in the Western world. We performed a genome-wide association study for alcohol-related cirrhosis in individuals of European descent (712 cases and 1,426 controls) with subsequent validation in two independe...

    journal_title:Nature genetics

    pub_type: 杂志文章


    authors: Buch S,Stickel F,Trépo E,Way M,Herrmann A,Nischalke HD,Brosch M,Rosendahl J,Berg T,Ridinger M,Rietschel M,McQuillin A,Frank J,Kiefer F,Schreiber S,Lieb W,Soyka M,Semmo N,Aigner E,Datz C,Schmelz R,Brückner S,Ze

    更新日期:2015-12-01 00:00:00

  • Genome-wide association study identifies three susceptibility loci for laryngeal squamous cell carcinoma in the Chinese population.

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    journal_title:Nature genetics

    pub_type: 杂志文章


    authors: Wei Q,Yu D,Liu M,Wang M,Zhao M,Liu M,Jia W,Ma H,Fang J,Xu W,Chen K,Xu Z,Wang J,Tian L,Yuan H,Chang J,Hu Z,Wei L,Huang Y,Han Y,Liu J,Han D,Shen H,Yang S,Zheng H,Ji Q,Li D,Tan W,Wu C,Lin D

    更新日期:2014-10-01 00:00:00

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    abstract::Systemic lupus erythematosus (SLE) is a complex autoimmune disease that causes substantial morbidity. As is typical for many other multifactorial disorders, much of the heritability of SLE remains unknown. We identified a rare autosomal recessive form of SLE, in which autozygome analysis revealed a null mutation in th...

    journal_title:Nature genetics

    pub_type: 杂志文章


    authors: Al-Mayouf SM,Sunker A,Abdwani R,Abrawi SA,Almurshedi F,Alhashmi N,Al Sonbul A,Sewairi W,Qari A,Abdallah E,Al-Owain M,Al Motywee S,Al-Rayes H,Hashem M,Khalak H,Al-Jebali L,Alkuraya FS

    更新日期:2011-10-23 00:00:00

  • Common variants in FOXP1 are associated with generalized vitiligo.

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    journal_title:Nature genetics

    pub_type: 杂志文章,多中心研究


    authors: Jin Y,Birlea SA,Fain PR,Mailloux CM,Riccardi SL,Gowan K,Holland PJ,Bennett DC,Wallace MR,McCormack WT,Kemp EH,Gawkrodger DJ,Weetman AP,Picardo M,Leone G,Taïeb A,Jouary T,Ezzedine K,van Geel N,Lambert J,Overbeck A

    更新日期:2010-07-01 00:00:00

  • Human Genome Variation 2006: emerging views on structural variation and large-scale SNP analysis.

    abstract::The eighth annual Human Genome Variation Meeting was held in September 2006 in the Hong Kong Special Administrative Region, China. The meeting highlighted recent advances in characterization of genetic variation, including genome-wide association studies and structural variation. ...

    journal_title:Nature genetics



    authors: Abecasis G,Tam PK,Bustamante CD,Ostrander EA,Scherer SW,Chanock SJ,Kwok PY,Brookes AJ

    更新日期:2007-02-01 00:00:00

  • Enhancer mutations and phenotype modularity.

    abstract::Only a few mutations in regulatory elements that cause human disease have been identified thus far. A new report identifies cis-regulatory mutations that abolish the activity of a developmental enhancer, thereby causing pancreatic agenesis. ...

    journal_title:Nature genetics

    pub_type: 评论,新闻


    authors: Gordon CT,Lyonnet S

    更新日期:2014-01-01 00:00:00

  • Triplication of a 21q22 region contributes to B cell transformation through HMGN1 overexpression and loss of histone H3 Lys27 trimethylation.

    abstract::Down syndrome confers a 20-fold increased risk of B cell acute lymphoblastic leukemia (B-ALL), and polysomy 21 is the most frequent somatic aneuploidy among all B-ALLs. Yet the mechanistic links between chromosome 21 triplication and B-ALL remain undefined. Here we show that germline triplication of only 31 genes orth...

    journal_title:Nature genetics

    pub_type: 杂志文章


    authors: Lane AA,Chapuy B,Lin CY,Tivey T,Li H,Townsend EC,van Bodegom D,Day TA,Wu SC,Liu H,Yoda A,Alexe G,Schinzel AC,Sullivan TJ,Malinge S,Taylor JE,Stegmaier K,Jaffe JD,Bustin M,te Kronnie G,Izraeli S,Harris MH,Steve

    更新日期:2014-06-01 00:00:00

  • The genomic landscape of high hyperdiploid childhood acute lymphoblastic leukemia.

    abstract::High hyperdiploid (51-67 chromosomes) acute lymphoblastic leukemia (ALL) is one of the most common childhood malignancies, comprising 30% of all pediatric B cell-precursor ALL. Its characteristic genetic feature is the nonrandom gain of chromosomes X, 4, 6, 10, 14, 17, 18 and 21, with individual trisomies or tetrasomi...

    journal_title:Nature genetics

    pub_type: 杂志文章


    authors: Paulsson K,Lilljebjörn H,Biloglav A,Olsson L,Rissler M,Castor A,Barbany G,Fogelstrand L,Nordgren A,Sjögren H,Fioretos T,Johansson B

    更新日期:2015-06-01 00:00:00

  • Adenovirus mediated expression of therapeutic plasma levels of human factor IX in mice.

    abstract::Gene therapy strategies designed to combat haemophilia B, caused by defects in clotting factor IX, have so far concentrated on ex vivo approaches. We have now evaluated adenoviral vector-mediated expression of human factor IX in vivo. Injection of the vector Av1H9B, which encodes human factor IX cDNA, into the tail ve...

    journal_title:Nature genetics

    pub_type: 杂志文章


    authors: Smith TA,Mehaffey MG,Kayda DB,Saunders JM,Yei S,Trapnell BC,McClelland A,Kaleko M

    更新日期:1993-12-01 00:00:00

  • Genomic and molecular characterization of esophageal squamous cell carcinoma.

    abstract::Esophageal squamous cell carcinoma (ESCC) is prevalent worldwide and particularly common in certain regions of Asia. Here we report the whole-exome or targeted deep sequencing of 139 paired ESCC cases, and analysis of somatic copy number variations (SCNV) of over 180 ESCCs. We identified previously uncharacterized mut...

    journal_title:Nature genetics

    pub_type: 杂志文章


    authors: Lin DC,Hao JJ,Nagata Y,Xu L,Shang L,Meng X,Sato Y,Okuno Y,Varela AM,Ding LW,Garg M,Liu LZ,Yang H,Yin D,Shi ZZ,Jiang YY,Gu WY,Gong T,Zhang Y,Xu X,Kalid O,Shacham S,Ogawa S,Wang MR,Koeffler HP

    更新日期:2014-05-01 00:00:00

  • Mesp2 initiates somite segmentation through the Notch signalling pathway.

    abstract::The Notch-signalling pathway is important in establishing metameric pattern during somitogenesis. In mice, the lack of either of two molecules involved in the Notch-signalling pathway, Mesp2 or presenilin-1 (Ps1), results in contrasting phenotypes: caudalized versus rostralized vertebra. Here we adopt a genetic approa...

    journal_title:Nature genetics

    pub_type: 杂志文章


    authors: Takahashi Y,Koizumi K,Takagi A,Kitajima S,Inoue T,Koseki H,Saga Y

    更新日期:2000-08-01 00:00:00

  • Population- and individual-specific regulatory variation in Sardinia.

    abstract::Genetic studies of complex traits have mainly identified associations with noncoding variants. To further determine the contribution of regulatory variation, we combined whole-genome and transcriptome data for 624 individuals from Sardinia to identify common and rare variants that influence gene expression and splicin...

    journal_title:Nature genetics

    pub_type: 杂志文章


    authors: Pala M,Zappala Z,Marongiu M,Li X,Davis JR,Cusano R,Crobu F,Kukurba KR,Gloudemans MJ,Reinier F,Berutti R,Piras MG,Mulas A,Zoledziewska M,Marongiu M,Sorokin EP,Hess GT,Smith KS,Busonero F,Maschio A,Steri M,Sidore

    更新日期:2017-05-01 00:00:00

  • A single natural nucleotide mutation alters bacterial pathogen host tropism.

    abstract::The capacity of microbial pathogens to alter their host tropism leading to epidemics in distinct host species populations is a global public and veterinary health concern. To investigate the molecular basis of a bacterial host-switching event in a tractable host species, we traced the evolutionary trajectory of the co...

    journal_title:Nature genetics

    pub_type: 杂志文章


    authors: Viana D,Comos M,McAdam PR,Ward MJ,Selva L,Guinane CM,González-Muñoz BM,Tristan A,Foster SJ,Fitzgerald JR,Penadés JR

    更新日期:2015-04-01 00:00:00