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.
Matsuzaka
Yasunari
Y
Department of Molecular Life Science, Tokai University School of Medicine, Bohseidai, Isehara, Kanagawa, Japan.
Tounai
Kenichi
K
Denda
Akihiro
A
Tomizawa
Maiko
M
Makino
Satoshi
S
Okamoto
Koichi
K
Keicho
Naoto
N
Oka
Akira
A
Kulski
Jerzy K
JK
Tamiya
Gen
G
Inoko
Hidetoshi
H
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