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Human Gene Mutation Database: towards a comprehensive central mutation database
  1. P D Stenson,
  2. E Ball,
  3. K Howells,
  4. A Phillips,
  5. M Mort,
  6. D N Cooper
  1. Institute of Medical Genetics, Cardiff University, Heath Park, Cardiff, UK
  1. P Stenson, Institute of Medical Genetics, Cardiff University, Heath Park, Cardiff CF15 8DW, UK; StensonPD{at}cardiff.ac.uk

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We write in response to a number of very specific criticisms of the Human Gene Mutation Database (HGMD; www.hgmd.org) made in the recently published article by George et al (see review on p 65).1 All seven claims made were amenable to empirical testing. Having tested these claims, we find all of them to be either false or highly misleading. In the text that follows, we refute or rebut each claim in turn.

HGMD represents an attempt to collate known (published) gene lesions responsible for human inherited disease. HGMD comprises various types of germ-line mutation within the coding, splicing and regulatory regions of human nuclear genes. HGMD currently (1 December 2007) contains 76 011 different mutations in 2876 human genes.

Claim 1: 143 genes are present in OMIM but have no corresponding HGMD entry Response—This claim is wholly misleading. OMIM (Online Mendelian Inheritance in Man) records many types of gene mutation which HGMD does not, such as somatic lesions, neutral polymorphisms and mitochondrial mutations. It is therefore to be expected that there will be some entries in OMIM that do not have a corresponding HGMD entry. We received the list of 143 genes from George et al and performed our own analysis. After careful comparison with OMIM, we found the following:

  • 33 genes (23.1%) contain only somatic allelic variants (for example, LEF1)

  • 29 genes (20.3%) contain variants exclusively from the mitochondrial genome (for example, MTCO2)

  • 8 genes (5.6%) contain exclusively normal polymorphic protein variants with no known disease association (for example, GPT)

  • 13 genes (9.1%) were actually present in HGMD at the time of the study, but, for whatever reason, had not been found by George et al (for example, CD2AP)

  • 12 genes (8.4%) were misidentified by George et al as having allelic variants in …

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