The Human Gene Mutation Database: Building a Comprehensive Mutation Repository for Clinical and Molecular Genetics, Diagnostic Testing and Personalized Genomic Medicine

Overview

Journal Hum Genet

Specialty Genetics

Date 2013 Oct 1

PMID 24077912

Citations 695

Authors

Peter D Stenson

Matthew Mort

Edward V Ball

Katy Shaw

Andrew Phillips

David N Cooper

Affiliations

Soon will be listed here.

Abstract

The Human Gene Mutation Database (HGMD®) is a comprehensive collection of germline mutations in nuclear genes that underlie, or are associated with, human inherited disease. By June 2013, the database contained over 141,000 different lesions detected in over 5,700 different genes, with new mutation entries currently accumulating at a rate exceeding 10,000 per annum. HGMD was originally established in 1996 for the scientific study of mutational mechanisms in human genes. However, it has since acquired a much broader utility as a central unified disease-oriented mutation repository utilized by human molecular geneticists, genome scientists, molecular biologists, clinicians and genetic counsellors as well as by those specializing in biopharmaceuticals, bioinformatics and personalized genomics. The public version of HGMD (http://www.hgmd.org) is freely available to registered users from academic institutions/non-profit organizations whilst the subscription version (HGMD Professional) is available to academic, clinical and commercial users under license via BIOBASE GmbH.

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References

Carter H, Douville C, Stenson P, Cooper D, Karchin R . Identifying Mendelian disease genes with the variant effect scoring tool. BMC Genomics. 2013; 14 Suppl 3:S3. PMC: 3665549. DOI: 10.1186/1471-2164-14-S3-S3. View

Abecasis G, Altshuler D, Auton A, Brooks L, Durbin R, Gibbs R . A map of human genome variation from population-scale sequencing. Nature. 2010; 467(7319):1061-73. PMC: 3042601. DOI: 10.1038/nature09534. View

Shihab H, Gough J, Cooper D, Stenson P, Barker G, Edwards K . Predicting the functional, molecular, and phenotypic consequences of amino acid substitutions using hidden Markov models. Hum Mutat. 2012; 34(1):57-65. PMC: 3558800. DOI: 10.1002/humu.22225. View

Amberger J, Bocchini C, Scott A, Hamosh A . McKusick's Online Mendelian Inheritance in Man (OMIM). Nucleic Acids Res. 2008; 37(Database issue):D793-6. PMC: 2686440. DOI: 10.1093/nar/gkn665. View

Flicek P, Ahmed I, Amode M, Barrell D, Beal K, Brent S . Ensembl 2013. Nucleic Acids Res. 2012; 41(Database issue):D48-55. PMC: 3531136. DOI: 10.1093/nar/gks1236. View

Lopes M, Joyce C, Ritchie G, John S, Cunningham F, Asimit J . A combined functional annotation score for non-synonymous variants. Hum Hered. 2012; 73(1):47-51. PMC: 3390741. DOI: 10.1159/000334984. View

Cooper D, Bacolla A, Ferec C, Vasquez K, Kehrer-Sawatzki H, Chen J . On the sequence-directed nature of human gene mutation: the role of genomic architecture and the local DNA sequence environment in mediating gene mutations underlying human inherited disease. Hum Mutat. 2011; 32(10):1075-99. PMC: 3177966. DOI: 10.1002/humu.21557. View

Wang X, Wei X, Thijssen B, Das J, Lipkin S, Yu H . Three-dimensional reconstruction of protein networks provides insight into human genetic disease. Nat Biotechnol. 2012; 30(2):159-64. PMC: 3708476. DOI: 10.1038/nbt.2106. View

Green R, Berg J, Grody W, Kalia S, Korf B, Martin C . ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing. Genet Med. 2013; 15(7):565-74. PMC: 3727274. DOI: 10.1038/gim.2013.73. View

10.

Cirulli E, Goldstein D . In vitro assays fail to predict in vivo effects of regulatory polymorphisms. Hum Mol Genet. 2007; 16(16):1931-9. DOI: 10.1093/hmg/ddm140. View

11.

Abecasis G, Auton A, Brooks L, DePristo M, Durbin R, Handsaker R . An integrated map of genetic variation from 1,092 human genomes. Nature. 2012; 491(7422):56-65. PMC: 3498066. DOI: 10.1038/nature11632. View

12.

Cooper D, Krawczak M, Polychronakos C, Tyler-Smith C, Kehrer-Sawatzki H . Where genotype is not predictive of phenotype: towards an understanding of the molecular basis of reduced penetrance in human inherited disease. Hum Genet. 2013; 132(10):1077-130. PMC: 3778950. DOI: 10.1007/s00439-013-1331-2. View

13.

Gonsalves S, Ng D, Johnston J, Teer J, Stenson P, Cooper D . Using exome data to identify malignant hyperthermia susceptibility mutations. Anesthesiology. 2013; 119(5):1043-53. PMC: 4077354. DOI: 10.1097/ALN.0b013e3182a8a8e7. View

14.

Peterson T, Doughty E, Kann M . Towards precision medicine: advances in computational approaches for the analysis of human variants. J Mol Biol. 2013; 425(21):4047-63. PMC: 3807015. DOI: 10.1016/j.jmb.2013.08.008. View

15.

Sherry S, Ward M, Kholodov M, Baker J, Phan L, Smigielski E . dbSNP: the NCBI database of genetic variation. Nucleic Acids Res. 2000; 29(1):308-11. PMC: 29783. DOI: 10.1093/nar/29.1.308. View

16.

Johnston J, Rubinstein W, Facio F, Ng D, Singh L, Teer J . Secondary variants in individuals undergoing exome sequencing: screening of 572 individuals identifies high-penetrance mutations in cancer-susceptibility genes. Am J Hum Genet. 2012; 91(1):97-108. PMC: 3397257. DOI: 10.1016/j.ajhg.2012.05.021. View

17.

Scally A, Dutheil J, Hillier L, Jordan G, Goodhead I, Herrero J . Insights into hominid evolution from the gorilla genome sequence. Nature. 2012; 483(7388):169-75. PMC: 3303130. DOI: 10.1038/nature10842. View

18.

Guo Y, Wei X, Das J, Grimson A, Lipkin S, Clark A . Dissecting disease inheritance modes in a three-dimensional protein network challenges the "guilt-by-association" principle. Am J Hum Genet. 2013; 93(1):78-89. PMC: 3710751. DOI: 10.1016/j.ajhg.2013.05.022. View

19.

Pruitt K, Tatusova T, Klimke W, Maglott D . NCBI Reference Sequences: current status, policy and new initiatives. Nucleic Acids Res. 2008; 37(Database issue):D32-6. PMC: 2686572. DOI: 10.1093/nar/gkn721. View

20.

Douville C, Carter H, Kim R, Niknafs N, Diekhans M, Stenson P . CRAVAT: cancer-related analysis of variants toolkit. Bioinformatics. 2013; 29(5):647-8. PMC: 3582272. DOI: 10.1093/bioinformatics/btt017. View