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Fine localization of a major disease-susceptibility locus for diffuse panbronchiolitis.

Diffuse panbronchiolitis affecting East Asians is strongly associated with the class I human leukocyte antigen (HLA) alleles. Recent observations suggest that a major disease-susceptibility gene may be located between the HLA-B and HLA-A loci in the class I region of the major histocompatibility complex on chromosome 6. To test this possibility, we analyzed 14 polymorphic markers in 92 Japanese patients and 93 healthy controls. Of these, seven marker alleles, including HLA-B54 and HLA-A11, were significantly associated with the disease. Maximum-likelihood haplotype analysis and subsequent direct determination of individual haplotypes identified a group of disease-associated haplotypes, one of which contained all seven disease-associated marker alleles. Another haplotype, containing HLA-B*5504, was also associated with the disease. All these haplotypes seem to have diverged from a common ancestral haplotype in East Asians and share a specific segment containing three consecutive markers between the S and TFIIH loci in the class I region. Furthermore, one of the markers within the candidate region showed the highest delta value, indicating the strongest association. Of 20 Korean patients with diffuse panbronchiolitis, 17 also shared the combination of the disease-associated marker alleles within the candidate region. These results indicate that an HLA-associated major susceptibility gene for diffuse panbronchiolitis is probably located within the 200 kb in the class I region 300 kb telomeric of the HLA-B locus on the chromosome 6p21.3.

Pubmed ID: 10677310 RIS Download

Mesh terms: Alleles | Bronchiolitis | Chromosome Mapping | Chromosomes, Human, Pair 6 | Female | Gene Frequency | Genetic Linkage | Genetic Predisposition to Disease | HLA-A Antigens | HLA-B Antigens | Haplotypes | Histocompatibility Antigens Class I | Humans | Japan | Korea | Likelihood Functions | Male | Microsatellite Repeats | Molecular Sequence Data | Odds Ratio | Polymorphism, Single Nucleotide | Transcription Factor TFIIH | Transcription Factors | Transcription Factors, TFII

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GenBank

NIH genetic sequence database that provides an annotated collection of all publicly available DNA sequences for almost 280 000 formally described species. (Jan 2014) These sequences are obtained primarily through submissions from individual laboratories and batch submissions from large-scale sequencing projects, including whole-genome shotgun (WGS) and environmental sampling projects. Most submissions are made using the web-based BankIt or standalone Sequin programs, and GenBank staff assigns accession numbers upon data receipt. It is part of the International Nucleotide Sequence Database Collaboration and daily data exchange with the European Nucleotide Archive (ENA) and the DNA Data Bank of Japan (DDBJ) ensures worldwide coverage. GenBank is accessible through the NCBI Entrez retrieval system, which integrates data from the major DNA and protein sequence databases along with taxonomy, genome, mapping, protein structure and domain information, and the biomedical journal literature via PubMed. BLAST provides sequence similarity searches of GenBank and other sequence databases. Complete bimonthly releases and daily updates of the GenBank database are available by FTP.

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