abstract：:We present a systematic review of pleiotropy among SNPs and genes reported to show genome-wide association with common complex diseases and traits. We find abundant evidence of pleiotropy; 233 (16.9%) genes and 77 (4.6%) SNPs show pleiotropic effects. SNP pleiotropic status was associated with gene location (p = 0.024...

journal_title：American journal of human genetics

authors： Sivakumaran S,Agakov F,Theodoratou E,Prendergast JG,Zgaga L,Manolio T,Rudan I,McKeigue P,Wilson JF,Campbell H

更新日期：2011-11-11 00:00:00

abstract：:Abdominal aortic aneurysm (AAA) is a common cause of morbidity and mortality and has a significant heritability. We carried out a genome-wide association discovery study of 1866 patients with AAA and 5435 controls and replication of promising signals (lead SNP with a p value < 1 × 10(-5)) in 2871 additional cases and ...

journal_title：American journal of human genetics

authors： Bown MJ,Jones GT,Harrison SC,Wright BJ,Bumpstead S,Baas AF,Gretarsdottir S,Badger SA,Bradley DT,Burnand K,Child AH,Clough RE,Cockerill G,Hafez H,Scott DJ,Futers S,Johnson A,Sohrabi S,Smith A,Thompson MM,van Bockxm

更新日期：2011-11-11 00:00:00

abstract：:The disease classification neurodegeneration with brain iron accumulation (NBIA) comprises a clinically and genetically heterogeneous group of progressive neurodegenerative disorders characterized by brain iron deposits in the basal ganglia. For about half of the cases, the molecular basis is currently unknown. We use...

journal_title：American journal of human genetics

authors： Hartig MB,Iuso A,Haack T,Kmiec T,Jurkiewicz E,Heim K,Roeber S,Tarabin V,Dusi S,Krajewska-Walasek M,Jozwiak S,Hempel M,Winkelmann J,Elstner M,Oexle K,Klopstock T,Mueller-Felber W,Gasser T,Trenkwalder C,Tiranti V,Kr

更新日期：2011-10-07 00:00:00

abstract：:Autosomal-recessive high-grade axial myopia was diagnosed in Bedouin Israeli consanguineous kindred. Some affected individuals also had variable expressivity of early-onset cataracts, peripheral vitreo-retinal degeneration, and secondary sight loss due to severe retinal detachments. Through genome-wide linkage analysi...

journal_title：American journal of human genetics

authors： Mordechai S,Gradstein L,Pasanen A,Ofir R,El Amour K,Levy J,Belfair N,Lifshitz T,Joshua S,Narkis G,Elbedour K,Myllyharju J,Birk OS

更新日期：2011-09-09 00:00:00

abstract：:Assignment of alleles to haplotypes for nearly all the variants on all chromosomes can be performed by genetic analysis of a nuclear family with three or more children. Whole-genome sequence data enable deterministic phasing of nearly all sequenced alleles by permitting assignment of recombinations to precise chromoso...

journal_title：American journal of human genetics

authors： Roach JC,Glusman G,Hubley R,Montsaroff SZ,Holloway AK,Mauldin DE,Srivastava D,Garg V,Pollard KS,Galas DJ,Hood L,Smit AF

更新日期：2011-09-09 00:00:00

abstract：:The study of recent natural selection in human populations has important applications to human history and medicine. Positive natural selection drives the increase in beneficial alleles and plays a role in explaining diversity across human populations. By discovering traits subject to positive selection, we can better...

journal_title：American journal of human genetics

authors： Bhatia G,Patterson N,Pasaniuc B,Zaitlen N,Genovese G,Pollack S,Mallick S,Myers S,Tandon A,Spencer C,Palmer CD,Adeyemo AA,Akylbekova EL,Cupples LA,Divers J,Fornage M,Kao WH,Lange L,Li M,Musani S,Mychaleckyj JC,Og

更新日期：2011-09-09 00:00:00

abstract：:Charcot-Marie-Tooth disease is characterized by length-dependent axonal degeneration with distal sensory loss and weakness, deep-tendon-reflex abnormalities, and skeletal deformities. It is caused by mutations in more than 40 genes. We investigated a four-generation family with 23 members affected by the axonal form (...

journal_title：American journal of human genetics

authors： Weedon MN,Hastings R,Caswell R,Xie W,Paszkiewicz K,Antoniadi T,Williams M,King C,Greenhalgh L,Newbury-Ecob R,Ellard S

更新日期：2011-08-12 00:00:00

abstract：:Genetic mutations responsible for oblique facial clefts (ObFC), a unique class of facial malformations, are largely unknown. We show that loss-of-function mutations in SPECC1L are pathogenic for this human developmental disorder and that SPECC1L is a critical organizer of vertebrate facial morphogenesis. During murine...

journal_title：American journal of human genetics

authors： Saadi I,Alkuraya FS,Gisselbrecht SS,Goessling W,Cavallesco R,Turbe-Doan A,Petrin AL,Harris J,Siddiqui U,Grix AW Jr,Hove HD,Leboulch P,Glover TW,Morton CC,Richieri-Costa A,Murray JC,Erickson RP,Maas RL

更新日期：2011-07-15 00:00:00

abstract：:Proteoglycans are a major component of extracellular matrix and contribute to normal embryonic and postnatal development by ensuring tissue stability and signaling functions. We studied five patients with recessive joint dislocations and congenital heart defects, including bicuspid aortic valve (BAV) and aortic root d...

journal_title：American journal of human genetics

authors： Baasanjav S,Al-Gazali L,Hashiguchi T,Mizumoto S,Fischer B,Horn D,Seelow D,Ali BR,Aziz SA,Langer R,Saleh AA,Becker C,Nürnberg G,Cantagrel V,Gleeson JG,Gomez D,Michel JB,Stricker S,Lindner TH,Nürnberg P,Sugahara K,

更新日期：2011-07-15 00:00:00

abstract：:Hermansky-Pudlak Syndrome (HPS) is an autosomal-recessive condition characterized by oculocutaneous albinism and a bleeding diathesis due to absent platelet delta granules. HPS is a genetically heterogeneous disorder of intracellular vesicle biogenesis. We first screened all our patients with HPS-like symptoms for mut...

journal_title：American journal of human genetics

authors： Cullinane AR,Curry JA,Carmona-Rivera C,Summers CG,Ciccone C,Cardillo ND,Dorward H,Hess RA,White JG,Adams D,Huizing M,Gahl WA

更新日期：2011-06-10 00:00:00

abstract：:Risk prediction based on genomic profiles has raised a lot of attention recently. However, family history is usually ignored in genetic risk prediction. In this study we proposed a statistical framework for risk prediction given an individual's genotype profile and family history. Genotype information about the relati...

journal_title：American journal of human genetics

authors： So HC,Kwan JS,Cherny SS,Sham PC

更新日期：2011-05-13 00:00:00

abstract：:We used whole-exome sequencing to study three individuals with a distinct condition characterized by short stature, chondrodysplasia with brachydactyly, congenital joint dislocations, cleft palate, and facial dysmorphism. Affected individuals carried homozygous missense mutations in IMPAD1, the gene coding for gPAPP, ...

journal_title：American journal of human genetics

authors： Vissers LE,Lausch E,Unger S,Campos-Xavier AB,Gilissen C,Rossi A,Del Rosario M,Venselaar H,Knoll U,Nampoothiri S,Nair M,Spranger J,Brunner HG,Bonafé L,Veltman JA,Zabel B,Superti-Furga A

更新日期：2011-05-13 00:00:00

abstract：:Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a leukodystrophy characterized by early-onset macrocephaly and delayed-onset neurological deterioration. Recessive MLC1 mutations are observed in 75% of patients with MLC. Genetic-linkage studies failed to identify another gene. We recently showed tha...

journal_title：American journal of human genetics

authors： López-Hernández T,Ridder MC,Montolio M,Capdevila-Nortes X,Polder E,Sirisi S,Duarri A,Schulte U,Fakler B,Nunes V,Scheper GC,Martínez A,Estévez R,van der Knaap MS

更新日期：2011-04-08 00:00:00

abstract：:Autosomal-recessive congenital ichthyoses represent a large and heterogeneous group of disorders of epidermal cornification. Recent data suggest that most of these disorders might result from defective lipid transport and metabolism. In the present study, we describe a late-onset form of recessive ichthyosis in a larg...

journal_title：American journal of human genetics

authors： Israeli S,Khamaysi Z,Fuchs-Telem D,Nousbeck J,Bergman R,Sarig O,Sprecher E

更新日期：2011-04-08 00:00:00

abstract：:Little is known about the genetics of nonsyndromic intellectual disability (NSID). We hypothesized that de novo mutations (DNMs) in synaptic genes explain an important fraction of sporadic NSID cases. In order to investigate this possibility, we sequenced 197 genes encoding glutamate receptors and a large subset of th...

journal_title：American journal of human genetics

authors： Hamdan FF,Gauthier J,Araki Y,Lin DT,Yoshizawa Y,Higashi K,Park AR,Spiegelman D,Dobrzeniecka S,Piton A,Tomitori H,Daoud H,Massicotte C,Henrion E,Diallo O,S2D Group.,Shekarabi M,Marineau C,Shevell M,Maranda B,Mitche

更新日期：2011-03-11 00:00:00

abstract：:The gene has been proposed as an attractive unit of analysis for association studies, but a simple yet valid, powerful, and sufficiently fast method of evaluating the statistical significance of all genes in large, genome-wide datasets has been lacking. Here we propose the use of an extended Simes test that integrates...

journal_title：American journal of human genetics

authors： Li MX,Gui HS,Kwan JS,Sham PC

更新日期：2011-03-11 00:00:00

abstract：:Cranial neural crest (CNC) is a multipotent migratory cell population that gives rise to most of the craniofacial bones. An intricate network mediates CNC formation, epithelial-mesenchymal transition, migration along distinct paths, and differentiation. Errors in these processes lead to craniofacial abnormalities, inc...

journal_title：American journal of human genetics

authors： Ghassibe-Sabbagh M,Desmyter L,Langenberg T,Claes F,Boute O,Bayet B,Pellerin P,Hermans K,Backx L,Mansilla MA,Imoehl S,Nowak S,Ludwig KU,Baluardo C,Ferrian M,Mossey PA,Noethen M,Dewerchin M,François G,Revencu N,Vanw

更新日期：2011-02-11 00:00:00

abstract：:Waardenburg anophthalmia syndrome, also known as microphthalmia with limb anomalies, ophthalmoacromelic syndrome, and anophthalmia-syndactyly, is a rare autosomal-recessive developmental disorder that has been mapped to 10p11.23. Here we show that this disease is heterogeneous by reporting on a consanguineous family, ...

journal_title：American journal of human genetics

authors： Abouzeid H,Boisset G,Favez T,Youssef M,Marzouk I,Shakankiry N,Bayoumi N,Descombes P,Agosti C,Munier FL,Schorderet DF

更新日期：2011-01-07 00:00:00

abstract：:Primary hyperoxaluria (PH) is an autosomal-recessive disorder of endogenous oxalate synthesis characterized by accumulation of calcium oxalate primarily in the kidney. Deficiencies of alanine-glyoxylate aminotransferase (AGT) or glyoxylate reductase (GRHPR) are the two known causes of the disease (PH I and II, respect...

journal_title：American journal of human genetics

authors： Belostotsky R,Seboun E,Idelson GH,Milliner DS,Becker-Cohen R,Rinat C,Monico CG,Feinstein S,Ben-Shalom E,Magen D,Weissman I,Charon C,Frishberg Y

更新日期：2010-09-10 00:00:00

abstract：:The lymphatic vasculature is essential for the recirculation of extracellular fluid, fat absorption, and immune function and as a route of tumor metastasis. The dissection of molecular mechanisms underlying lymphangiogenesis has been accelerated by the identification of tissue-specific lymphatic endothelial markers an...

journal_title：American journal of human genetics

authors： Au AC,Hernandez PA,Lieber E,Nadroo AM,Shen YM,Kelley KA,Gelb BD,Diaz GA

更新日期：2010-09-10 00:00:00

abstract：:Heteroplasmy, the existence of multiple mtDNA types within an individual, has been previously detected by using mostly indirect methods and focusing largely on just the hypervariable segments of the control region. Next-generation sequencing technologies should enable studies of heteroplasmy across the entire mtDNA ge...

journal_title：American journal of human genetics

authors： Li M,Schönberg A,Schaefer M,Schroeder R,Nasidze I,Stoneking M

更新日期：2010-08-13 00:00:00

abstract：:False-positive or false-negative results attributable to undetected genotyping errors and confounding factors present a constant challenge for genome-wide association studies (GWAS) given the low signals associated with complex phenotypes and the noise associated with high-throughput genotyping. In the context of the ...

journal_title：American journal of human genetics

authors： Pluzhnikov A,Below JE,Konkashbaev A,Tikhomirov A,Kistner-Griffin E,Roe CA,Nicolae DL,Cox NJ

更新日期：2010-07-09 00:00:00

abstract：:Lymphedema is the clinical manifestation of defects in lymphatic structure or function. Mutations identified in genes regulating lymphatic development result in inherited lymphedema. No mutations have yet been identified in genes mediating lymphatic function that result in inherited lymphedema. Survey microarray studi...

journal_title：American journal of human genetics

authors： Ferrell RE,Baty CJ,Kimak MA,Karlsson JM,Lawrence EC,Franke-Snyder M,Meriney SD,Feingold E,Finegold DN

更新日期：2010-06-11 00:00:00

abstract：:Urinary voiding dysfunction in childhood, manifesting as incontinence, dysuria, and urinary frequency, is a common condition. Urofacial syndrome (UFS) is a rare autosomal recessive disease characterized by facial grimacing when attempting to smile and failure of the urinary bladder to void completely despite a lack of...

journal_title：American journal of human genetics

authors： Daly SB,Urquhart JE,Hilton E,McKenzie EA,Kammerer RA,Lewis M,Kerr B,Stuart H,Donnai D,Long DA,Burgu B,Aydogdu O,Derbent M,Garcia-Minaur S,Reardon W,Gener B,Shalev S,Smith R,Woolf AS,Black GC,Newman WG

更新日期：2010-06-11 00:00:00

abstract：:Genomic rearrangements involving the peripheral myelin protein gene (PMP22) in human chromosome 17p12 are associated with neuropathy: duplications cause Charcot-Marie-Tooth disease type 1A (CMT1A), whereas deletions lead to hereditary neuropathy with liability to pressure palsies (HNPP). Our previous studies showed th...

journal_title：American journal of human genetics

authors： Zhang F,Seeman P,Liu P,Weterman MA,Gonzaga-Jauregui C,Towne CF,Batish SD,De Vriendt E,De Jonghe P,Rautenstrauss B,Krause KH,Khajavi M,Posadka J,Vandenberghe A,Palau F,Van Maldergem L,Baas F,Timmerman V,Lupski JR

更新日期：2010-06-11 00:00:00

abstract：:Increasing public interest in direct-to-consumer (DTC) genetic ancestry testing has been accompanied by growing concern about issues ranging from the personal and societal implications of the testing to the scientific validity of ancestry inference. The very concept of "ancestry" is subject to misunderstanding in both...

journal_title：American journal of human genetics

authors： Royal CD,Novembre J,Fullerton SM,Goldstein DB,Long JC,Bamshad MJ,Clark AG

更新日期：2010-05-14 00:00:00

abstract：:More than 270 million people worldwide have hearing loss that affects normal communication. Although astonishing progress has been made in the identification of more than 50 genes for deafness during the past decade, the majority of deafness genes are yet to be identified. In this study, we mapped a previously unknown...

journal_title：American journal of human genetics

authors： Sirmaci A,Erbek S,Price J,Huang M,Duman D,Cengiz FB,Bademci G,Tokgöz-Yilmaz S,Hişmi B,Ozdağ H,Oztürk B,Kulaksizoğlu S,Yildirim E,Kokotas H,Grigoriadou M,Petersen MB,Shahin H,Kanaan M,King MC,Chen ZY,Blanton SH,L

更新日期：2010-05-14 00:00:00

abstract：:GWAS have been successful in identifying disease susceptibility loci, but it remains a challenge to pinpoint the causal variants in subsequent fine-mapping studies. A conventional fine-mapping effort starts by sequencing dozens of randomly selected samples at susceptibility loci to discover candidate variants, which a...

journal_title：American journal of human genetics

authors： Wang K,Dickson SP,Stolle CA,Krantz ID,Goldstein DB,Hakonarson H

更新日期：2010-05-14 00:00:00

abstract：:Distal hereditary motor neuropathies comprise a clinically and genetically heterogeneous group of disorders. We recently mapped an X-linked form of this condition to chromosome Xq13.1-q21 in two large unrelated families. The region of genetic linkage included ATP7A, which encodes a copper-transporting P-type ATPase mu...

journal_title：American journal of human genetics

authors： Kennerson ML,Nicholson GA,Kaler SG,Kowalski B,Mercer JF,Tang J,Llanos RM,Chu S,Takata RI,Speck-Martins CE,Baets J,Almeida-Souza L,Fischer D,Timmerman V,Taylor PE,Scherer SS,Ferguson TA,Bird TD,De Jonghe P,Feely SM,

更新日期：2010-03-12 00:00:00

abstract：:Genome-wide association studies are routinely conducted to identify genetic variants that influence complex disorders. It is well known that failure to properly account for population or pedigree structure can lead to spurious association as well as reduced power. We propose a method, ROADTRIPS, for case-control assoc...

journal_title：American journal of human genetics

authors： Thornton T,McPeek MS

更新日期：2010-02-12 00:00:00

abstract：:DNA methylation is assumed to be complementary on both alleles across the genome, although there are exceptions, notably in regions subject to genomic imprinting. We present a genome-wide survey of the degree of allelic skewing of DNA methylation with the aim of identifying previously unreported differentially methyla...

journal_title：American journal of human genetics

authors： Schalkwyk LC,Meaburn EL,Smith R,Dempster EL,Jeffries AR,Davies MN,Plomin R,Mill J

更新日期：2010-02-12 00:00:00

abstract：:Patients with Joubert syndrome 2 (JBTS2) suffer from a neurological disease manifested by psychomotor retardation, hypotonia, ataxia, nystagmus, and oculomotor apraxia and variably associated with dysmorphism, as well as retinal and renal involvement. Brain MRI results show cerebellar vermis hypoplasia and additional ...

journal_title：American journal of human genetics

authors： Edvardson S,Shaag A,Zenvirt S,Erlich Y,Hannon GJ,Shanske AL,Gomori JM,Ekstein J,Elpeleg O

更新日期：2010-01-01 00:00:00

abstract：:Genetic defects affecting motility of cilia and flagella cause chronic destructive airway disease, randomization of left-right body asymmetry, and, frequently, male infertility in primary ciliary dyskinesia (PCD). The most frequent defects involve outer and inner dynein arms (ODAs and IDAs) that are large multiprotein...

journal_title：American journal of human genetics

authors： Loges NT,Olbrich H,Becker-Heck A,Häffner K,Heer A,Reinhard C,Schmidts M,Kispert A,Zariwala MA,Leigh MW,Knowles MR,Zentgraf H,Seithe H,Nürnberg G,Nürnberg P,Reinhardt R,Omran H

更新日期：2009-12-01 00:00:00

abstract：:We report on the identification of a 0.3 Mb inherited recurrent but variable copy-number gain at Xq28 in affected males of four unrelated families with X-linked mental retardation (MR). All aberrations segregate with the disease in the families, and the carrier mothers show nonrandom X chromosome inactivation. Tiling ...

journal_title：American journal of human genetics

authors： Vandewalle J,Van Esch H,Govaerts K,Verbeeck J,Zweier C,Madrigal I,Mila M,Pijkels E,Fernandez I,Kohlhase J,Spaich C,Rauch A,Fryns JP,Marynen P,Froyen G

更新日期：2009-12-01 00:00:00

abstract：:We present a novel method for simultaneous genotype calling and haplotype-phase inference. Our method employs the computationally efficient BEAGLE haplotype-frequency model, which can be applied to large-scale studies with millions of markers and thousands of samples. We compare genotype calls made with our method to ...

journal_title：American journal of human genetics

authors： Browning BL,Yu Z

更新日期：2009-12-01 00:00:00

abstract：:A modified alpha-N-acetylgalactosaminidase (NAGA) with alpha-galactosidase A (GLA)-like substrate specificity was designed on the basis of structural studies and was produced in Chinese hamster ovary cells. The enzyme acquired the ability to catalyze the degradation of 4-methylumbelliferyl-alpha-D-galactopyranoside. I...

journal_title：American journal of human genetics

authors： Tajima Y,Kawashima I,Tsukimura T,Sugawara K,Kuroda M,Suzuki T,Togawa T,Chiba Y,Jigami Y,Ohno K,Fukushige T,Kanekura T,Itoh K,Ohashi T,Sakuraba H

更新日期：2009-11-01 00:00:00

abstract：:We report recessive mutations in the gene for the latent transforming growth factor-beta binding protein 4 (LTBP4) in four unrelated patients with a human syndrome disrupting pulmonary, gastrointestinal, urinary, musculoskeletal, craniofacial, and dermal development. All patients had severe respiratory distress, with ...

journal_title：American journal of human genetics

authors： Urban Z,Hucthagowder V,Schürmann N,Todorovic V,Zilberberg L,Choi J,Sens C,Brown CW,Clark RD,Holland KE,Marble M,Sakai LY,Dabovic B,Rifkin DB,Davis EC

更新日期：2009-11-01 00:00:00

abstract：:The critical importance of cytoskeletal function for correct neuronal migration during development of the cerebral cortex has been underscored by the identities of germline mutations underlying a number of human neurodevelopmental disorders. The proteins affected include TUBA1A, a major alpha-tubulin isoform, and micr...

journal_title：American journal of human genetics

authors： Abdollahi MR,Morrison E,Sirey T,Molnar Z,Hayward BE,Carr IM,Springell K,Woods CG,Ahmed M,Hattingh L,Corry P,Pilz DT,Stoodley N,Crow Y,Taylor GR,Bonthron DT,Sheridan E

更新日期：2009-11-01 00:00:00

abstract：:Shovel shape of upper incisors is a common characteristic in Asian and Native American populations but is rare or absent in African and European populations. Like other common dental traits, genetic polymorphisms involved in the tooth shoveling have not yet been clarified. In ectodysplasin A receptor (EDAR), where dys...

journal_title：American journal of human genetics

authors： Kimura R,Yamaguchi T,Takeda M,Kondo O,Toma T,Haneji K,Hanihara T,Matsukusa H,Kawamura S,Maki K,Osawa M,Ishida H,Oota H

更新日期：2009-10-01 00:00:00

abstract：:Spinal muscular atrophy (SMA) is a common autosomal-recessive motor neuron disease caused by the homozygous loss of the SMN1 gene. A nearly identical gene, SMN2, has been shown to decrease the severity of SMA in a dose-dependent manner. However SMN2 is not the sole phenotypic modifier, because there are discrepant SMA...

journal_title：American journal of human genetics

authors： Prior TW,Krainer AR,Hua Y,Swoboda KJ,Snyder PC,Bridgeman SJ,Burghes AH,Kissel JT

更新日期：2009-09-01 00:00:00