Genomic variation in a global village: report of the 10th annual Human Genome Variation Meeting 2008.


:The Centre for Applied Genomics of the Hospital for Sick Children and the University of Toronto hosted the 10th Human Genome Variation (HGV) Meeting in Toronto, Canada, in October 2008, welcoming about 240 registrants from 34 countries. During the 3 days of plenary workshops, keynote address, and poster sessions, a strong cross-disciplinary trend was evident, integrating expertise from technology and computation, through biology and medicine, to ethics and law. Single nucleotide polymorphisms (SNPs) as well as the larger copy number variants (CNVs) are recognized by ever-improving array and next-generation sequencing technologies, and the data are being incorporated into studies that are increasingly genome-wide as well as global in scope. A greater challenge is to convert data to information, through databases, and to use the information for greater understanding of human variation. In the wake of publications of the first individual genome sequences, an inaugural public forum provided the opportunity to debate whether we are ready for personalized medicine through direct-to-consumer testing. The HGV meetings foster collaboration, and fruits of the interactions from 2008 are anticipated for the 11th annual meeting in September 2009.


Hum Mutat


Human mutation


Brookes AJ,Chanock SJ,Hudson TJ,Peltonen L,Abecasis G,Kwok PY,Scherer SW




Has Abstract


2009-07-01 00:00:00












  • Identification and computationally-based structural interpretation of naturally occurring variants of human protein C.

    abstract::Protein C (PC) is a key regulator of blood clotting and inflammation. Its inherited deficiency is associated with venous thromboembolism, and recombinant activated PC is currently used to increase survival in severe sepsis. The molecular basis of inherited PC deficiency is heterogeneous. Due to its multiple physiologi...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Rovida E,Merati G,D'Ursi P,Zanardelli S,Marino F,Fontana G,Castaman G,Faioni EM

    更新日期:2007-04-01 00:00:00

  • Genetic lesions of bilirubin uridine-diphosphoglucuronate glucuronosyltransferase (UGT1A1) causing Crigler-Najjar and Gilbert syndromes: correlation of genotype to phenotype.

    abstract::Uridine-diphosphoglucuronate glucuronosyltransferases (UGTs) are a family of enzymes that conjugate various endogenous and exogenous compounds with glucuronic acid and facilitate their excretion in the bile. Bilirubin-UGT(1) (UGT1A1) is the only isoform that significantly contributes to the conjugation of bilirubin. L...

    journal_title:Human mutation

    pub_type: 杂志文章,评审


    authors: Kadakol A,Ghosh SS,Sappal BS,Sharma G,Chowdhury JR,Chowdhury NR

    更新日期:2000-10-01 00:00:00

  • Level of heteroplasmy for the mitochondrial mutation A3243G correlates with age at onset of diabetes and deafness.

    abstract::The mitochondrial mutation A3243G has been shown to be associated with a syndrome of diabetes mellitus and sensorineural hearing loss. Using a solid-phase-based sequencing method we have investigated the relation between the proportion of mutant mitochondrial genomes and the time of disease onset among members of thre...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Olsson C,Zethelius B,Lagerström-Fermér M,Asplund J,Berne C,Landegren U

    更新日期:1998-01-01 00:00:00

  • Kilquist syndrome: A novel syndromic hearing loss disorder caused by homozygous deletion of SLC12A2.

    abstract::Syndromic sensorineural hearing loss is multigenic and associated with malformations of the ear and other organ systems. Herein we describe a child admitted to the NIH Undiagnosed Diseases Program with global developmental delay, sensorineural hearing loss, gastrointestinal abnormalities, and absent salivation. Next-g...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Macnamara EF,Koehler AE,D'Souza P,Estwick T,Lee P,Vezina G,Undiagnosed Diseases Network.,Fauni H,Braddock SR,Torti E,Holt JM,Sharma P,Malicdan MCV,Tifft CJ

    更新日期:2019-05-01 00:00:00

  • PCR-based detection of minority point mutations.

    abstract::The need for detection of minority mutations (i.e., a few mutants within a high excess of wild-type alleles) arises frequently in the field of cancer and molecular genetics. Current mutation detection technologies are limited by several technical factors when it comes to the detection of minority point mutations, incl...

    journal_title:Human mutation

    pub_type: 杂志文章,评审


    authors: Mike Makrigiorgos G

    更新日期:2004-05-01 00:00:00

  • The 185delAG mutation (c.68_69delAG) in the BRCA1 gene triggers translation reinitiation at a downstream AUG codon.

    abstract::The 185delAG mutation (c.68_69delAG; ter39) in the BRCA1 gene is a founder Jewish Ashkenazi mutation that is carried by 1% of this population and has been identified in thousands of breast or ovarian cancer patients. We have previously described that transcripts bearing this mutation, as well as transcripts bearing th...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Buisson M,Anczuków O,Zetoune AB,Ware MD,Mazoyer S

    更新日期:2006-10-01 00:00:00

  • Repopulation of rho0 cells with mitochondria from a patient with a mitochondrial DNA point mutation in tRNA(Gly) results in respiratory chain dysfunction.

    abstract::Familial hypertrophic ventricular cardiomyopathy has been demonstrated to be associated with a number of mitochondrial DNA (mtDNA) mutations. A fibroblast cell line carrying a mutation in its mtDNA at position 9997 in the gene encoding tRNA glycine was obtained from a patient with hypertrophic cardiomyopathy. To demon...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Raha S,Merante F,Shoubridge E,Myint AT,Tein I,Benson L,Johns T,Robinson BH

    更新日期:1999-01-01 00:00:00

  • Filamin B Loss-of-Function Mutation in Dimerization Domain Causes Autosomal-Recessive Spondylocarpotarsal Synostosis Syndrome with Rib Anomalies.

    abstract::Spondylocarpotarsal synostosis syndrome (SCT) is a distinct group of disorders characterized by short stature, disrupted vertebral segmentation with vertebral fusion, scoliosis, lordosis, carpal/tarsal synostosis, and lack of rib anomalies. Mutations in filamin B (FLNB) and MYH3 have been reported for autosomal-recess...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Yang CF,Wang CH,Siong H'ng W,Chang CP,Lin WD,Chen YT,Wu JY,Tsai FJ

    更新日期:2017-05-01 00:00:00

  • MSeqDR: A Centralized Knowledge Repository and Bioinformatics Web Resource to Facilitate Genomic Investigations in Mitochondrial Disease.

    abstract::MSeqDR is the Mitochondrial Disease Sequence Data Resource, a centralized and comprehensive genome and phenome bioinformatics resource built by the mitochondrial disease community to facilitate clinical diagnosis and research investigations of individual patient phenotypes, genomes, genes, and variants. A central Web ...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Shen L,Diroma MA,Gonzalez M,Navarro-Gomez D,Leipzig J,Lott MT,van Oven M,Wallace DC,Muraresku CC,Zolkipli-Cunningham Z,Chinnery PF,Attimonelli M,Zuchner S,Falk MJ,Gai X

    更新日期:2016-06-01 00:00:00

  • Diagnostic exome sequencing to elucidate the genetic basis of likely recessive disorders in consanguineous families.

    abstract::Rare, atypical, and undiagnosed autosomal-recessive disorders frequently occur in the offspring of consanguineous couples. Current routine diagnostic genetic tests fail to establish a diagnosis in many cases. We employed exome sequencing to identify the underlying molecular defects in patients with unresolved but puta...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Makrythanasis P,Nelis M,Santoni FA,Guipponi M,Vannier A,Béna F,Gimelli S,Stathaki E,Temtamy S,Mégarbané A,Masri A,Aglan MS,Zaki MS,Bottani A,Fokstuen S,Gwanmesia L,Aliferis K,Bustamante Eduardo M,Stamoulis G,Psoni S

    更新日期:2014-10-01 00:00:00

  • NKX2-1 mutations leading to surfactant protein promoter dysregulation cause interstitial lung disease in "Brain-Lung-Thyroid Syndrome".

    abstract::NKX2-1 (NK2 homeobox 1) is a critical regulator of transcription for the surfactant protein (SP)-B and -C genes (SFTPB and SFTPC, respectively). We identified and functionally characterized two new de novo NKX2-1 mutations c.493C>T (p.R165W) and c.786_787del2 (p.L263fs) in infants with closely similar severe interstit...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Guillot L,Carré A,Szinnai G,Castanet M,Tron E,Jaubert F,Broutin I,Counil F,Feldmann D,Clement A,Polak M,Epaud R

    更新日期:2010-02-01 00:00:00

  • Quantitative analysis of SMN1 and SMN2 genes based on DHPLC: a highly efficient and reliable carrier-screening test.

    abstract::Autosomal recessive spinal muscular atrophy (SMA) is a common, fatal neuromuscular disease caused by homozygous absence of the SMN1 gene in approximately 94% of patients. However, a highly homologous SMN2 gene exists in the same chromosome interval, centromeric to SMN1, and hampers detection of SMN1. We present a new,...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Su YN,Hung CC,Li H,Lee CN,Cheng WF,Tsao PN,Chang MC,Yu CL,Hsieh WS,Lin WL,Hsu SM

    更新日期:2005-05-01 00:00:00

  • GRIN database: A unified and manually curated repertoire of GRIN variants.

    abstract::Glutamatergic neurotransmission is crucial for brain development, wiring neuronal function, and synaptic plasticity mechanisms. Recent genetic studies showed the existence of autosomal dominant de novo GRIN gene variants associated with GRIN-related disorders (GRDs), a rare pediatric neurological disorder caused by N-...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: García-Recio A,Santos-Gómez A,Soto D,Julia-Palacios N,García-Cazorla À,Altafaj X,Olivella M

    更新日期:2020-11-30 00:00:00

  • Molecular basis of congenital erythropoietic porphyria: mutations in the human uroporphyrinogen III synthase gene.

    abstract::Congenital erythropoietic porphyria (CEP) is an autosomal recessive inborn error of metabolism that results from the markedly deficient activity of the fourth enzyme in the heme biosynthetic pathway, uroporphyrinogen III synthase (URO-synthase). To date, 17 mutations have been described including 11 missense, one nons...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Xu W,Astrin KH,Desnick RJ

    更新日期:1996-01-01 00:00:00

  • Enigmatic in vivo iduronate-2-sulfatase (IDS) mutant transcript correction to wild-type in Hunter syndrome.

    abstract::Sequence analysis of the X-linked iduronate-2-sulfatase (IDS) gene in two Hunter syndrome patients revealed a lack of concordance between IDS genomic DNA and cDNA. These individuals were found to be hemizygous respectively for a nonsense mutation [c.22C>T;p.R8X] and a frameshift micro-insertion [c.10insT;p.P4Sfs] in t...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Lualdi S,Tappino B,Di Duca M,Dardis A,Anderson CJ,Biassoni R,Thompson PW,Corsolini F,Di Rocco M,Bembi B,Regis S,Cooper DN,Filocamo M

    更新日期:2010-04-01 00:00:00

  • Wolfram syndrome in French population: characterization of novel mutations and polymorphisms in the WFS1 gene.

    abstract::Wolfram syndrome (WS), a rare autosomal recessive neurodegenerative disorder, results in most cases from mutations in the WFS1 gene. In this study, a total of 19 patients with Wolfram syndrome and 36 relatives from 17 families were screened for mutations in the WFS1 gene. WFS1 mutations were identified on both alleles...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Giuliano F,Bannwarth S,Monnot S,Cano A,Chabrol B,Vialettes B,Delobel B,Paquis-Flucklinger V,French Group of WS.

    更新日期:2005-01-01 00:00:00

  • Fanconi anemia A due to a novel frameshift mutation in hotspot motifs: lack of FANCA protein.

    abstract::Homozygosity for a frameshift mutation at codon 1213 of FANCA gene was identified in a Turkish patient. Immunoprecipitation-western blot analysis showed the complete absence of the FANCA protein band. This novel mutation, a deletion of T at position 3639 in exon 37 (3639delT), is responsible for the disease and causes...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Balta G,de Winter JP,Kayserili H,Pronk JC,Joenje H

    更新日期:2000-06-01 00:00:00

  • LTBP2 mutations cause Weill-Marchesani and Weill-Marchesani-like syndrome and affect disruptions in the extracellular matrix.

    abstract::Latent transforming growth factor (TGF) beta-binding protein 2 (LTBP2) is an extracellular matrix (ECM) protein that associates with fibrillin-1 containing microfibrils. Various factors prompted considering LTBP2 in the etiology of isolated ectopia lentis and associated conditions such as Weill-Marchesani syndrome (WM...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Haji-Seyed-Javadi R,Jelodari-Mamaghani S,Paylakhi SH,Yazdani S,Nilforushan N,Fan JB,Klotzle B,Mahmoudi MJ,Ebrahimian MJ,Chelich N,Taghiabadi E,Kamyab K,Boileau C,Paisan-Ruiz C,Ronaghi M,Elahi E

    更新日期:2012-08-01 00:00:00

  • Describing structural changes by extending HGVS sequence variation nomenclature.

    abstract::New technologies allow rapid discovery of novel sequence variants among which those involving complex structural rearrangements. The description of such complex variants challenges the existing standard sequence variation nomenclature of the Human Genome Variation Society (HGVS,, because ...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Taschner PE,den Dunnen JT

    更新日期:2011-05-01 00:00:00

  • Genetic diversity from a limited repertoire of mutations on different common allelic backgrounds: alpha 1-antitrypsin deficiency variant Pduarte.

    abstract::alpha 1-Antitrypsin (alpha 1AT) is one of the most polymorphic gene loci in the human genome. alpha 1AT variants are typically identified by their migration position in an isoelectric focusing gel at pH 4-5. Heterogeneity of the isoelectric point of alpha 1AT variants, hence variant migration, most often results from ...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Hildesheim J,Kinsley G,Bissell M,Pierce J,Brantly M

    更新日期:1993-01-01 00:00:00

  • Genetic and functional analyses of ZIC3 variants in congenital heart disease.

    abstract::Mutations in zinc-finger in cerebellum 3 (ZIC3) result in heterotaxy or isolated congenital heart disease (CHD). The majority of reported mutations cluster in zinc-finger domains. We previously demonstrated that many of these lead to aberrant ZIC3 subcellular trafficking. A relative paucity of N- and C-terminal mutati...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Cowan J,Tariq M,Ware SM

    更新日期:2014-01-01 00:00:00

  • A pharmacogenetic approach to identify mutant forms of α-galactosidase A that respond to a pharmacological chaperone for Fabry disease.

    abstract::Fabry disease is caused by mutations in the gene (GLA) that encodes α-galactosidase A (α-Gal A). The iminosugar AT1001 (GR181413A, migalastat hydrochloride, 1-deoxygalactonojirimycin) is a pharmacological chaperone that selectively binds and stabilizes α-Gal A, increasing total cellular levels and activity for some mu...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Wu X,Katz E,Della Valle MC,Mascioli K,Flanagan JJ,Castelli JP,Schiffmann R,Boudes P,Lockhart DJ,Valenzano KJ,Benjamin ER

    更新日期:2011-08-01 00:00:00

  • Mutations of the CEP290 gene encoding a centrosomal protein cause Meckel-Gruber syndrome.

    abstract::Meckel-Gruber syndrome (MKS) is an autosomal recessive, lethal multisystemic disorder characterized by meningooccipital encephalocele, cystic kidney dysplasia, hepatobiliary ductal plate malformation, and postaxial polydactyly. Recently, genes for MKS1 and MKS3 were identified, putting MKS on the list of ciliary disor...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Frank V,den Hollander AI,Brüchle NO,Zonneveld MN,Nürnberg G,Becker C,Du Bois G,Kendziorra H,Roosing S,Senderek J,Nürnberg P,Cremers FP,Zerres K,Bergmann C

    更新日期:2008-01-01 00:00:00

  • A functional polymorphism in the pre-miR-146a gene is associated with the risk of nonsyndromic orofacial cleft.

    abstract::microRNAs (miRNAs) are widely involved in craniofacial development, and genetic variants of miRNAs may be associated with the risk of nonsyndromic orofacial cleft (NSOC). Here, we systematically selected five single nucleotide polymorphisms (SNPs) of miRNAs and investigated the associations between these variants and ...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Pan Y,Li D,Lou S,Zhang C,Du Y,Jiang H,Zhang W,Ma L,Wang L

    更新日期:2018-05-01 00:00:00

  • Prioritizing Variants in Complete Hereditary Breast and Ovarian Cancer Genes in Patients Lacking Known BRCA Mutations.

    abstract::BRCA1 and BRCA2 testing for hereditary breast and ovarian cancer (HBOC) does not identify all pathogenic variants. Sequencing of 20 complete genes in HBOC patients with uninformative test results (N = 287), including noncoding and flanking sequences of ATM, BARD1, BRCA1, BRCA2, CDH1, CHEK2, EPCAM, MLH1, MRE11A, MSH2, ...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Caminsky NG,Mucaki EJ,Perri AM,Lu R,Knoll JH,Rogan PK

    更新日期:2016-07-01 00:00:00

  • Effects of a 9.6-kb deletion of the LDL receptor gene (FH Helsinki) on structure and levels of mRNA.

    abstract::FH Helsinki is a deletion of the low-density lipoprotein receptor (LDLR) gene that deletes 9.6 kb from intron 15 to exon 18. Screening for mutant transcripts by Northern blot analysis from a patient heterozygous for FH Helsinki revealed two mutant transcripts. One was a transcript where the proximal part of intron 15 ...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Rødningen OK,Tonstad S,Ose L,Berg K,Leren TP

    更新日期:1998-01-01 00:00:00

  • A single, large deletion accounts for all the beta-globin gene mutations in twenty families from Sabah (North Borneo), Malaysia. Mutation in brief no. 240. Online.

    abstract::Beta-thalassemia major is one of the commonest genetic disorders in South-East Asia. The spectrum of beta-thalassemia mutations in the various ethnic sub-populations on the island of Borneo is unknown. We studied 20 Dusun children from the East Malaysian state of Sabah (North Borneo) with a severe beta-thalassemia maj...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Thong MK,Rudzki Z,Hall J,Tan JA,Chan LL,Yap SF

    更新日期:1999-01-01 00:00:00

  • Functional analysis of splicing mutations and of an exon 2 polymorphic variant of SERPING1/C1NH.

    abstract::Several sequence changes have been reported in hereditary angioedema patients in intron 2 of the SERPING1/C1NH gene, but their consequences on splicing have not been determined. We examined in cell transfection assays the consequences at the mRNA level of splicing mutations affecting either the +3 or the +5 donor site...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Duponchel C,Djenouhat K,Frémeaux-Bacchi V,Monnier N,Drouet C,Tosi M

    更新日期:2006-03-01 00:00:00

  • Comparative analysis and functional mapping of SACS mutations reveal novel insights into sacsin repeated architecture.

    abstract::Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a neurological disease with mutations in SACS, encoding sacsin, a multidomain protein of 4,579 amino acids. The large size of SACS and its translated protein has hindered biochemical analysis of ARSACS, and how mutant sacsins lead to disease remains...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Romano A,Tessa A,Barca A,Fattori F,de Leva MF,Terracciano A,Storelli C,Santorelli FM,Verri T

    更新日期:2013-03-01 00:00:00

  • Mutation nomenclature in practice: findings and recommendations from the cystic fibrosis external quality assessment scheme.

    abstract::Currently, two nomenclature systems are in use to describe sequence variants for cystic fibrosis: the established traditional nomenclature system and the more recent Human Genome Variation Society (HGVS) nomenclature system. We have evaluated the use of both systems in the laboratory reports of 217 participants in the...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Berwouts S,Morris MA,Girodon E,Schwarz M,Stuhrmann M,Dequeker E

    更新日期:2011-11-01 00:00:00