The Human Gene Mutation Database (HGMD) and Its Exploitation in the Fields of Personalized Genomics and Molecular Evolution

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Abstract

The Human Gene Mutation Database (HGMD) constitutes a comprehensive core collection of data on germ?line mutations in nuclear genes underlying or associated with human inherited disease (http://www.hgmd.org). Data cataloged include single?base?pair substitutions in coding, regulatory, and splicing?relevant regions, micro?deletions and micro?insertions, indels, and triplet repeat expansions, as well as gross gene deletions, insertions, duplications, and complex rearrangements. Each mutation is entered into HGMD only once, in order to avoid confusion between recurrent and identical?by?descent lesions. By March 2012, the database contained in excess of 123,600 different lesions (HGMD Professional release 2012.1) detected in 4,514 different nuclear genes, with new entries currently accumulating at a rate in excess of 10,000 per annum. ?6,000 of these entries constitute disease?associated and functional polymorphisms. HGMD also includes cDNA reference sequences for more than 98% of the listed genes. Curr. Protoc. Bioinform. 39:1.13.1?1.13.20. © 2012 by John Wiley & Sons, Inc.

Keywords: HGMD; mutation; database; inherited disease; gene

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Figure 1.13.1 The HGMD home page.

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Figure 1.13.2 Example of a gene page for the factor VIII ( F8 ) gene. All mutation data, plus external links, can be accessed through this page.

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Figure 1.13.3 Example of missense/nonsense mutation data for the F8 gene. HGMD accession number, codon number, nucleotide change, amino acid change, phenotype, links to references and curatorial comments are provided.

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Figure 1.13.4 Example of splice mutation data for the F8 gene. HGMD accession number, IVS number, location (expressed relative to the donor or acceptor splice site), nucleotide substitution, phenotype, links to references, and curatorial comments are provided.

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Figure 1.13.5 Example of regulatory mutation data for the F8 gene. The nucleotide change is shown with 30 bp of flanking sequence either side. Phenotype, HGMD accession number, relative location, reference data, and curatorial comments are also provided.

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Figure 1.13.6 Example of micro‐deletion mutation data for the F8 gene. The deletion is shown with 10 bp of flanking sequence either side. The caret (⁁) marks the preceding complete codon (number provided). HGMD accession number, phenotype, links to references, and curatorial comments are also provided.

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Figure 1.13.7 Example of micro‐insertion mutation data for the F8 gene. HGMD accession number, location (nucleotide/codon), inserted base(s), phenotype, links to references, and curatorial comments are provided.

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Figure 1.13.8 Example of small indel mutation data for the F8 gene. The indel is shown with 10 bp of flanking sequence either side of the deleted bases. Inserted bases are in lowercase. The caret (⁁) marks the preceding complete codon (number provided). HGMD accession number, phenotype, links to references, and curatorial comments are also provided.

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Figure 1.13.9 Example of gross deletion mutation data for the F8 gene. A narrative‐style description, phenotype, links to references, and curatorial comments are provided.

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Figure 1.13.10 Example of gross insertion mutation data for the F8 gene. A narrative‐style description, phenotype, links to references, and curatorial comments are provided.

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Figure 1.13.11 Example of complex mutation data for the F8 gene. A narrative‐style description, phenotype, links to references, and curatorial comments are provided.

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Literature Cited

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