Original Article

Journal of Investigative Dermatology (1992) 99, 697–702; doi:10.1111/1523-1747.ep12614149

The Two Size Alleles of Human Keratin 1 Are Due to a Deletion in the Glycine-Rich Carboxyl-Terminal V2 Subdomain

Bernhard P Korge1, John G Compton1, Peter M Steinert1 and Dietmar Mischke2

  1. 1Skin Biology Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, U.S.A.
  2. 2Institute for Experimental Oncology and Transplantation Medicine, University Medical Center Rudolf Virchow, Free University of Berlin, Berlin, F.R.G.

Received 21 August 1992; Accepted 16 September 1992.

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Abstract

Two size variants of the type II human keratin 1 protein chain, termed 1a and 1b, have been described previously. Using amplification of genomic DNA by the polymerase chain reaction and sequence analysis we show here that the difference between these two alleles is due to a deletion of 21 bp in sequences encoding the V2 subdomain. This deletion corresponds to an entire glycine loop of seven amino acids. Pedigree analysis showed that the alleles are inherited as normal Mendelian traits. No additional alleles were detected in a survey of 88 alleles from 44 unrelated individuals, and the allelic frequency of 1a and 1b was 0.61 and 0.39. To determine the molecular basis of inherited dermatoses it is preferable to perform genetic linkage studies utilizing candidate genes directly as polymorphic markers. The PCR-based keratin 1 alleles characterized here, together with previously described PCR-based size variants in the keratin 10 gene, provide useful markers for the keratin clusters on chromosome 12 and 17, respectively.

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