Identification of novel candidate genes in the diffuse panbronchiolitis critical region of the class I human MHC.
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.
Department of Molecular Life Science, Tokai University School of Medicine, Bohseidai, Isehara, Kanagawa, Japan.
Yasunari
Y
Matsuzaka
Kenichi
K
Tounai
Akihiro
A
Denda
Maiko
M
Tomizawa
Satoshi
S
Makino
Koichi
K
Okamoto
Naoto
N
Keicho
Akira
A
Oka
Jerzy K
JK
Kulski
Gen
G
Tamiya
Hidetoshi
H
Inoko
D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D002874:Chromosome Mapping; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D020869:Gene Expression Profiling; D005805:Genes, MHC Class I; D005807:Genes, Overlapping; D020022:Genetic Predisposition to Disease; D015235:HLA-B Antigens / Q000235:genetics*; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry; D008969:Molecular Sequence Data; D009077:Mucins; D016366:Open Reading Frames; D009928:Organ Specificity; D011062:Polynucleotide Adenylyltransferase; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000235:genetics*; D029424:Pulmonary Disease, Chronic Obstructive / Q000208:ethnology / Q000235:genetics*; D016372:RNA, Antisense / Q000096:biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic
D018076:DNA, Complementary; D015235:HLA-B Antigens; C113783:HLA-B54 antigen; C466100:MUCL3 protein, human; D008565:Membrane Proteins; D009077:Mucins; D011506:Proteins; D016372:RNA, Antisense; D012333:RNA, Messenger; C096806:zonadhesin; D011062:Polynucleotide Adenylyltransferase; C466099:TENT5A protein, human