Identification of novel candidate genes in the diffuse panbronchiolitis critical region of the class I human MHC

Immunogenetics. 2002 Aug;54(5):301-9. doi: 10.1007/s00251-002-0470-8. Epub 2002 Jul 9.

Abstract

Diffuse panbronchiolitis (DPB) is an unusual form of bronchiolar disease affecting exclusively East Asians. Strong associations of DPB with the class I human leukocyte antigens HLA-B54 in Japan and China and HLA-A11 in Korea suggest that the susceptible locus for DPB is located between the HLA-B and HLA-A genes. We have previously reported that the susceptibility gene for DPB could be localized within a 200-kb segment between the S and TFIIH loci in the HLA class I region, using refined microsatellite-based association mapping. However, no genes have been recognized in this candidate region to date. In order to identify a novel candidate gene for DPB from this segment, the expressed sequence tag databases were searched using the genomic sequence. As a result, a cDNA clone was isolated from a human lung cDNA library. This gene, designated C6orf37 (Chromosome 6 open reading frame 37), spans approximately 2.5 kb and consists of two exons encoding a 235-amino acid protein, sharing homology with the mucin-like domain of human zonadhesin, which is a sperm multiple-domain transmembrane protein with the sperm zona pellucida binding activity. Unexpectedly, RT-PCR analysis detected transcripts from the anti-sense DNA strand of this C6orf37 locus. The gene designated as C6orf37OS (C6orf37 Opposite Strand) and represented by these anti-sense transcripts contained no open reading frame. The transcripts from C6orf37 and C6orf37OS were observed in numerous tissues, with most-abundant expression in lung, kidney, and testis. Taken together, these results, especially the abundant expression in lung, indicate that C6orf37 and C6orf37OS are excellent candidate genes for DPB.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Asian People / genetics
  • Base Sequence
  • Chromosome Mapping
  • Chromosomes, Human, Pair 6 / genetics*
  • Cloning, Molecular
  • DNA, Complementary / genetics
  • Gene Expression Profiling
  • Genes, MHC Class I
  • Genes, Overlapping*
  • Genetic Predisposition to Disease
  • HLA-B Antigens / genetics*
  • Humans
  • Membrane Proteins / chemistry
  • Molecular Sequence Data
  • Mucins
  • Open Reading Frames
  • Organ Specificity
  • Polynucleotide Adenylyltransferase
  • Protein Structure, Tertiary
  • Proteins / genetics*
  • Pulmonary Disease, Chronic Obstructive / ethnology
  • Pulmonary Disease, Chronic Obstructive / genetics*
  • RNA, Antisense / biosynthesis
  • RNA, Antisense / genetics*
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Transcription, Genetic

Substances

  • DNA, Complementary
  • HLA-B Antigens
  • HLA-B54 antigen
  • MUCL3 protein, human
  • Membrane Proteins
  • Mucins
  • Proteins
  • RNA, Antisense
  • RNA, Messenger
  • zonadhesin
  • Polynucleotide Adenylyltransferase
  • TENT5A protein, human

Associated data

  • GENBANK/AB064272