Small island, big genetic discoveries.


: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, in studying the genetics of complex human phenotypes.


Nat Genet


Nature genetics


Lettre G,Hirschhorn JN




Has Abstract


2015-11-01 00:00:00














  • Exome sequencing identifies recurrent mutations in NF1 and RASopathy genes in sun-exposed melanomas.

    abstract::We report on whole-exome sequencing (WES) of 213 melanomas. Our analysis established NF1, encoding a negative regulator of RAS, as the third most frequently mutated gene in melanoma, after BRAF and NRAS. Inactivating NF1 mutations were present in 46% of melanomas expressing wild-type BRAF and RAS, occurred in older pa...

    journal_title:Nature genetics

    pub_type: 杂志文章


    authors: Krauthammer M,Kong Y,Bacchiocchi A,Evans P,Pornputtapong N,Wu C,McCusker JP,Ma S,Cheng E,Straub R,Serin M,Bosenberg M,Ariyan S,Narayan D,Sznol M,Kluger HM,Mane S,Schlessinger J,Lifton RP,Halaban R

    更新日期:2015-09-01 00:00:00

  • Mutations in the gene encoding gap junction protein beta-3 associated with autosomal dominant hearing impairment.

    abstract::Hearing impairment is the most commonly occurring condition that affects the ability of humans to communicate. More than 50% of the cases of profound early-onset deafness are caused by genetic factors. Over 40 loci for non-syndromic deafness have been genetically mapped, and mutations in several genes have been shown ...

    journal_title:Nature genetics

    pub_type: 杂志文章


    authors: Xia JH,Liu CY,Tang BS,Pan Q,Huang L,Dai HP,Zhang BR,Xie W,Hu DX,Zheng D,Shi XL,Wang DA,Xia K,Yu KP,Liao XD,Feng Y,Yang YF,Xiao JY,Xie DH,Huang JZ

    更新日期:1998-12-01 00:00:00

  • Epilepsy and brain abnormalities in mice lacking the Otx1 gene.

    abstract::The morphogenesis of the brain and the differentiation of the neural structures are highly complex processes. A series of temporally and spatially regulated morphogenetic events gives rise to smaller areas that are phylogenetically, functionally and often morphogenetically different. Candidate genes for positional inf...

    journal_title:Nature genetics

    pub_type: 杂志文章


    authors: Acampora D,Mazan S,Avantaggiato V,Barone P,Tuorto F,Lallemand Y,Brûlet P,Simeone A

    更新日期:1996-10-01 00:00:00

  • A mouse model of human L1 retrotransposition.

    abstract::The L1 retrotransposon has had an immense impact on the size and structure of the human genome through a variety of mechanisms, including insertional mutagenesis. To study retrotransposition in a living organism, we created a mouse model of human L1 retrotransposition. Here we show that L1 elements can retrotranspose ...

    journal_title:Nature genetics

    pub_type: 杂志文章


    authors: Ostertag EM,DeBerardinis RJ,Goodier JL,Zhang Y,Yang N,Gerton GL,Kazazian HH Jr

    更新日期:2002-12-01 00:00:00

  • RAF1 mutations in childhood-onset dilated cardiomyopathy.

    abstract::Dilated cardiomyopathy (DCM) is a highly heterogeneous trait with sarcomeric gene mutations predominating. The cause of a substantial percentage of DCMs remains unknown, and no gene-specific therapy is available. On the basis of resequencing of 513 DCM cases and 1,150 matched controls from various cohorts of distinct ...

    journal_title:Nature genetics

    pub_type: 杂志文章


    authors: Dhandapany PS,Razzaque MA,Muthusami U,Kunnoth S,Edwards JJ,Mulero-Navarro S,Riess I,Pardo S,Sheng J,Rani DS,Rani B,Govindaraj P,Flex E,Yokota T,Furutani M,Nishizawa T,Nakanishi T,Robbins J,Limongelli G,Hajjar RJ,L

    更新日期:2014-06-01 00:00:00

  • Rescue of embryonic lethality in Mdm4-null mice by loss of Trp53 suggests a nonoverlapping pathway with MDM2 to regulate p53.

    abstract::The p53 protein can inhibit cell cycling or induce apoptosis, and is thus a critical regulator of tumorigenesis. This protein is negatively regulated by a physical interaction with MDM2, an E3 ubiquitin ligase. This interaction is critical for cell viability; loss of Mdm2 causes cell death in vitro and in vivo in a p5...

    journal_title:Nature genetics

    pub_type: 杂志文章


    authors: Parant J,Chavez-Reyes A,Little NA,Yan W,Reinke V,Jochemsen AG,Lozano G

    更新日期:2001-09-01 00:00:00

  • The peripheral myelin protein gene PMP-22 is contained within the Charcot-Marie-Tooth disease type 1A duplication.

    abstract::Charcot-Marie-Tooth disease (CMT1) is the most common form of inherited peripheral neuropathy. Although the disease is genetically heterogeneous, it has been demonstrated that the gene defect is the most frequent type (CMT1A) is the result of a partial duplication of band 17p11.2. Recent studies suggested that the per...

    journal_title:Nature genetics

    pub_type: 杂志文章


    authors: Timmerman V,Nelis E,Van Hul W,Nieuwenhuijsen BW,Chen KL,Wang S,Ben Othman K,Cullen B,Leach RJ,Hanemann CO

    更新日期:1992-06-01 00:00:00

  • Genetic variants at 6p21.33 are associated with susceptibility to follicular lymphoma.

    abstract::We conducted genome-wide association studies of non-Hodgkin lymphoma using Illumina HumanHap550 BeadChips to identify subtype-specific associations in follicular, diffuse large B-cell and chronic lymphocytic leukemia/small lymphocytic lymphomas. We found that rs6457327 on 6p21.33 was associated with susceptibility to ...

    journal_title:Nature genetics

    pub_type: 杂志文章


    authors: Skibola CF,Bracci PM,Halperin E,Conde L,Craig DW,Agana L,Iyadurai K,Becker N,Brooks-Wilson A,Curry JD,Spinelli JJ,Holly EA,Riby J,Zhang L,Nieters A,Smith MT,Brown KM

    更新日期:2009-08-01 00:00:00

  • Plasmodium falciparum genome-wide scans for positive selection, recombination hot spots and resistance to antimalarial drugs.

    abstract::Antimalarial drugs impose strong selective pressure on Plasmodium falciparum parasites and leave signatures of selection in the parasite genome; screening for genes under selection may suggest potential drug or immune targets. Genome-wide association studies (GWAS) of parasite traits have been hampered by the lack of ...

    journal_title:Nature genetics

    pub_type: 杂志文章


    authors: Mu J,Myers RA,Jiang H,Liu S,Ricklefs S,Waisberg M,Chotivanich K,Wilairatana P,Krudsood S,White NJ,Udomsangpetch R,Cui L,Ho M,Ou F,Li H,Song J,Li G,Wang X,Seila S,Sokunthea S,Socheat D,Sturdevant DE,Porcella SF

    更新日期:2010-03-01 00:00:00

  • Genetic variation of a bacterial pathogen within individuals with cystic fibrosis provides a record of selective pressures.

    abstract::Advances in sequencing technologies have enabled the identification of mutations acquired by bacterial pathogens during infection. However, it remains unclear whether adaptive mutations fix in the population or lead to pathogen diversification within the patient. Here we study the genotypic diversity of Burkholderia d...

    journal_title:Nature genetics

    pub_type: 杂志文章


    authors: Lieberman TD,Flett KB,Yelin I,Martin TR,McAdam AJ,Priebe GP,Kishony R

    更新日期:2014-01-01 00:00:00

  • Mutations in the gene for transglutaminase 1 in autosomal recessive lamellar ichthyosis.

    abstract::We recently mapped the disease locus for severe autosomal recessive lamellar ichthyosis (LI) to chromosome 14q11 and showed complete linkage with TGM1, the gene encoding transglutaminase 1. We have now identified point mutations in TGM1 in two of the multiplex LI families used in the linkage study. Each nucleotide cha...

    journal_title:Nature genetics

    pub_type: 杂志文章


    authors: Russell LJ,DiGiovanna JJ,Rogers GR,Steinert PM,Hashem N,Compton JG,Bale SJ

    更新日期:1995-03-01 00:00:00

  • The Arabidopsis lyrata genome sequence and the basis of rapid genome size change.

    abstract::We report the 207-Mb genome sequence of the North American Arabidopsis lyrata strain MN47 based on 8.3× dideoxy sequence coverage. We predict 32,670 genes in this outcrossing species compared to the 27,025 genes in the selfing species Arabidopsis thaliana. The much smaller 125-Mb genome of A. thaliana, which diverged ...

    journal_title:Nature genetics

    pub_type: 杂志文章


    authors: Hu TT,Pattyn P,Bakker EG,Cao J,Cheng JF,Clark RM,Fahlgren N,Fawcett JA,Grimwood J,Gundlach H,Haberer G,Hollister JD,Ossowski S,Ottilar RP,Salamov AA,Schneeberger K,Spannagl M,Wang X,Yang L,Nasrallah ME,Bergelson J

    更新日期:2011-05-01 00:00:00

  • The apolipoprotein(a) gene is regulated by sex hormones and acute-phase inducers in YAC transgenic mice.

    abstract::High plasma concentrations of apolipoprotein (a) (apo(a)) have been implicated as a major independent risk factor for atherosclerosis in humans. Apo(a) is a large, evolutionarily new gene (present primarily in primates) for which considerable controversy exists concerning the factors that regulate its expression. To i...

    journal_title:Nature genetics

    pub_type: 杂志文章


    authors: Frazer KA,Narla G,Zhang JL,Rubin EM

    更新日期:1995-04-01 00:00:00

  • A component of the transcriptional repressor MeCP1 shares a motif with DNA methyltransferase and HRX proteins.

    abstract::Methylation of cytosines within the sequence CpG is essential for mouse development and has been linked to transcriptional suppression in vertebrate systems. Methyl-CpG binding proteins (MeCPs) 1 and 2 bind preferentially to methylated DNA and can inhibit transcription. The gene for MeCP2 has been cloned and a methyl-...

    journal_title:Nature genetics

    pub_type: 杂志文章


    authors: Cross SH,Meehan RR,Nan X,Bird A

    更新日期:1997-07-01 00:00:00

  • A genome-wide association study identifies two new cervical cancer susceptibility loci at 4q12 and 17q12.

    abstract::To identify new genetic risk factors for cervical cancer, we conducted a genome-wide association study in the Han Chinese population. The initial discovery set included 1,364 individuals with cervical cancer (cases) and 3,028 female controls, and we selected a 'stringently matched samples' subset (829 cases and 990 co...

    journal_title:Nature genetics

    pub_type: 杂志文章


    authors: Shi Y,Li L,Hu Z,Li S,Wang S,Liu J,Wu C,He L,Zhou J,Li Z,Hu T,Chen Y,Jia Y,Wang S,Wu L,Cheng X,Yang Z,Yang R,Li X,Huang K,Zhang Q,Zhou H,Tang F,Chen Z,Shen J,Jiang J,Ding H,Xing H,Zhang S,Qu P,S

    更新日期:2013-08-01 00:00:00

  • Probabilistic fine-mapping of transcriptome-wide association studies.

    abstract::Transcriptome-wide association studies using predicted expression have identified thousands of genes whose locally regulated expression is associated with complex traits and diseases. In this work, we show that linkage disequilibrium induces significant gene-trait associations at non-causal genes as a function of the ...

    journal_title:Nature genetics

    pub_type: 杂志文章


    authors: Mancuso N,Freund MK,Johnson R,Shi H,Kichaev G,Gusev A,Pasaniuc B

    更新日期:2019-04-01 00:00:00

  • A genome-wide association study identifies new susceptibility loci for esophageal adenocarcinoma and Barrett's esophagus.

    abstract::Esophageal adenocarcinoma is a cancer with rising incidence and poor survival. Most such cancers arise in a specialized intestinal metaplastic epithelium, which is diagnostic of Barrett's esophagus. In a genome-wide association study, we compared esophageal adenocarcinoma cases (n = 2,390) and individuals with precanc...

    journal_title:Nature genetics

    pub_type: 杂志文章


    authors: Levine DM,Ek WE,Zhang R,Liu X,Onstad L,Sather C,Lao-Sirieix P,Gammon MD,Corley DA,Shaheen NJ,Bird NC,Hardie LJ,Murray LJ,Reid BJ,Chow WH,Risch HA,Nyrén O,Ye W,Liu G,Romero Y,Bernstein L,Wu AH,Casson AG,Chano

    更新日期:2013-12-01 00:00:00

  • Testing for genetic associations in arbitrarily structured populations.

    abstract::We present a new statistical test of association between a trait and genetic markers, which we theoretically and practically prove to be robust to arbitrarily complex population structure. The statistical test involves a set of parameters that can be directly estimated from large-scale genotyping data, such as those m...

    journal_title:Nature genetics

    pub_type: 杂志文章


    authors: Song M,Hao W,Storey JD

    更新日期:2015-05-01 00:00:00

  • Molecular landmarks of tumor hypoxia across cancer types.

    abstract::Many primary-tumor subregions have low levels of molecular oxygen, termed hypoxia. Hypoxic tumors are at elevated risk for local failure and distant metastasis, but the molecular hallmarks of tumor hypoxia remain poorly defined. To fill this gap, we quantified hypoxia in 8,006 tumors across 19 tumor types. In ten tumo...

    journal_title:Nature genetics

    pub_type: 杂志文章


    authors: Bhandari V,Hoey C,Liu LY,Lalonde E,Ray J,Livingstone J,Lesurf R,Shiah YJ,Vujcic T,Huang X,Espiritu SMG,Heisler LE,Yousif F,Huang V,Yamaguchi TN,Yao CQ,Sabelnykova VY,Fraser M,Chua MLK,van der Kwast T,Liu SK,Bout

    更新日期:2019-02-01 00:00:00

  • Mice lacking both subunits of lysosomal beta-hexosaminidase display gangliosidosis and mucopolysaccharidosis.

    abstract::The GM2 gangliosidoses, Tay-Sachs and Sandhoff diseases, are caused by mutations in the HEXA (alpha-subunit) and HEXB (beta-subunit) genes, respectively. Each gene encodes a subunit for the heterodimeric lysosomal enzyme, beta-hexosaminidase A (alpha beta), as well as for the homodimers beta-hexosaminidase B (beta bet...

    journal_title:Nature genetics

    pub_type: 杂志文章


    authors: Sango K,McDonald MP,Crawley JN,Mack ML,Tifft CJ,Skop E,Starr CM,Hoffmann A,Sandhoff K,Suzuki K,Proia RL

    更新日期:1996-11-01 00:00:00

  • Association of the INS VNTR with size at birth. ALSPAC Study Team. Avon Longitudinal Study of Pregnancy and Childhood.

    abstract::Size at birth is an important determinant of perinatal survival and has also been associated with the risk for cardiovascular disease and type 2 diabetes in adult life. Common genetic variation that regulates fetal growth could therefore influence perinatal survival and predispose to the development of adult disease. ...

    journal_title:Nature genetics

    pub_type: 杂志文章


    authors: Dunger DB,Ong KK,Huxtable SJ,Sherriff A,Woods KA,Ahmed ML,Golding J,Pembrey ME,Ring S,Bennett ST,Todd JA

    更新日期:1998-05-01 00:00:00

  • Genome-wide association study of flowering time and grain yield traits in a worldwide collection of rice germplasm.

    abstract::A high-density haplotype map recently enabled a genome-wide association study (GWAS) in a population of indica subspecies of Chinese rice landraces. Here we extend this methodology to a larger and more diverse sample of 950 worldwide rice varieties, including the Oryza sativa indica and Oryza sativa japonica subspecie...

    journal_title:Nature genetics

    pub_type: 杂志文章


    authors: Huang X,Zhao Y,Wei X,Li C,Wang A,Zhao Q,Li W,Guo Y,Deng L,Zhu C,Fan D,Lu Y,Weng Q,Liu K,Zhou T,Jing Y,Si L,Dong G,Huang T,Lu T,Feng Q,Qian Q,Li J,Han B

    更新日期:2011-12-04 00:00:00

  • Wt1 is required for cardiovascular progenitor cell formation through transcriptional control of Snail and E-cadherin.

    abstract::The epicardial epithelial-mesenchymal transition (EMT) is hypothesized to generate cardiovascular progenitor cells that differentiate into various cell types, including coronary smooth muscle and endothelial cells, perivascular and cardiac interstitial fibroblasts and cardiomyocytes. Here we show that an epicardial-sp...

    journal_title:Nature genetics

    pub_type: 杂志文章


    authors: Martínez-Estrada OM,Lettice LA,Essafi A,Guadix JA,Slight J,Velecela V,Hall E,Reichmann J,Devenney PS,Hohenstein P,Hosen N,Hill RE,Muñoz-Chapuli R,Hastie ND

    更新日期:2010-01-01 00:00:00

  • Mutations in the xeroderma pigmentosum group D DNA repair/transcription gene in patients with trichothiodystrophy.

    abstract::DNA repair defects in the xeroderma pigmentosum (XP) group D complementation group can be associated with the clinical features of two quite different disorders; XP, a sun-sensitive and cancer-prone disorder, or trichothiodystrophy (TTD) which is characterized by sulphur-deficient brittle hair and a variety of other a...

    journal_title:Nature genetics

    pub_type: 杂志文章


    authors: Broughton BC,Steingrimsdottir H,Weber CA,Lehmann AR

    更新日期:1994-06-01 00:00:00

  • A systems analysis of mutational effects in HIV-1 protease and reverse transcriptase.

    abstract::The development of a quantitative understanding of viral evolution and the fitness landscape in HIV-1 drug resistance is a formidable challenge given the large number of available drugs and drug resistance mutations. We analyzed a dataset measuring the in vitro fitness of 70,081 virus samples isolated from HIV-1 subty...

    journal_title:Nature genetics

    pub_type: 杂志文章


    authors: Hinkley T,Martins J,Chappey C,Haddad M,Stawiski E,Whitcomb JM,Petropoulos CJ,Bonhoeffer S

    更新日期:2011-05-01 00:00:00

  • A missense mutation in TFRC, encoding transferrin receptor 1, causes combined immunodeficiency.

    abstract::Patients with a combined immunodeficiency characterized by normal numbers but impaired function of T and B cells had a homozygous p.Tyr20His substitution in transferrin receptor 1 (TfR1), encoded by TFRC. The substitution disrupts the TfR1 internalization motif, resulting in defective receptor endocytosis and markedly...

    journal_title:Nature genetics

    pub_type: 杂志文章


    authors: Jabara HH,Boyden SE,Chou J,Ramesh N,Massaad MJ,Benson H,Bainter W,Fraulino D,Rahimov F,Sieff C,Liu ZJ,Alshemmari SH,Al-Ramadi BK,Al-Dhekri H,Arnaout R,Abu-Shukair M,Vatsayan A,Silver E,Ahuja S,Davies EG,Sola-Visne

    更新日期:2016-01-01 00:00:00

  • Conditional and joint multiple-SNP analysis of GWAS summary statistics identifies additional variants influencing complex traits.

    abstract::We present an approximate conditional and joint association analysis that can use summary-level statistics from a meta-analysis of genome-wide association studies (GWAS) and estimated linkage disequilibrium (LD) from a reference sample with individual-level genotype data. Using this method, we analyzed meta-analysis s...

    journal_title:Nature genetics

    pub_type: 杂志文章


    authors: Yang J,Ferreira T,Morris AP,Medland SE,Genetic Investigation of ANthropometric Traits (GIANT) Consortium.,DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium.,Madden PA,Heath AC,Martin NG,Montgomery GW,Weedon MN,Lo

    更新日期:2012-03-18 00:00:00

  • A specific requirement for PDGF-C in palate formation and PDGFR-alpha signaling.

    abstract::PDGF-C is a member of the platelet-derived growth factor (PDGF) family, which signals through PDGF receptor (PDGFR) alphaalpha and alphabeta dimers. Here we show that Pdgfc(-/-) mice die in the perinatal period owing to feeding and respiratory difficulties associated with a complete cleft of the secondary palate. This...

    journal_title:Nature genetics

    pub_type: 杂志文章


    authors: Ding H,Wu X,Boström H,Kim I,Wong N,Tsoi B,O'Rourke M,Koh GY,Soriano P,Betsholtz C,Hart TC,Marazita ML,Field LL,Tam PP,Nagy A

    更新日期:2004-10-01 00:00:00

  • The genomic landscape of schwannoma.

    abstract::Schwannomas are common peripheral nerve sheath tumors that can cause debilitating morbidities. We performed an integrative analysis to determine genomic aberrations common to sporadic schwannomas. Exome sequence analysis with validation by targeted DNA sequencing of 125 samples uncovered, in addition to expected NF2 d...

    journal_title:Nature genetics

    pub_type: 杂志文章


    authors: Agnihotri S,Jalali S,Wilson MR,Danesh A,Li M,Klironomos G,Krieger JR,Mansouri A,Khan O,Mamatjan Y,Landon-Brace N,Tung T,Dowar M,Li T,Bruce JP,Burrell KE,Tonge PD,Alamsahebpour A,Krischek B,Agarwalla PK,Bi WL,Dun

    更新日期:2016-11-01 00:00:00

  • A somatic-mutational process recurrently duplicates germline susceptibility loci and tissue-specific super-enhancers in breast cancers.

    abstract::Somatic rearrangements contribute to the mutagenized landscape of cancer genomes. Here, we systematically interrogated rearrangements in 560 breast cancers by using a piecewise constant fitting approach. We identified 33 hotspots of large (>100 kb) tandem duplications, a mutational signature associated with homologous...

    journal_title:Nature genetics

    pub_type: 杂志文章


    authors: Glodzik D,Morganella S,Davies H,Simpson PT,Li Y,Zou X,Diez-Perez J,Staaf J,Alexandrov LB,Smid M,Brinkman AB,Rye IH,Russnes H,Raine K,Purdie CA,Lakhani SR,Thompson AM,Birney E,Stunnenberg HG,van de Vijver MJ,Marten

    更新日期:2017-03-01 00:00:00