Identification of novel candidate genes in the diffuse panbronchiolitis critical region of the class I human MHC
Identification of novel candidate genes in the diffuse panbronchiolitis critical region of the class I human MHC
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DOI：
10.1007/s00251-002-0470-8
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发表时间：
2002-08-01
期刊：
影响因子：
3.2
通讯作者：
Inoko, H
中科院分区：
文献类型：
--
作者：
Matsuzaka, Y;Tounai, K;Inoko, H
弥漫性泛细支气管炎（DPB）是一种罕见的细支疾病，仅影响东亚人。DPB与日本和中国的I类人白细胞抗原HLA-B54以及韩国的HLA-A11有很强的相关性，这表明DPB的易感位点位于HLA-B和HLA-A基因之间。我们之前曾报道，利用基于微卫星的关联图谱，DPB的易感基因可以定位在HLA I类区域S和TFIIH位点之间200 kb的片段中。然而，到目前为止，还没有在这个候选区域中发现基因。为了从该片段中找到新的DPB候选基因，利用基因组序列对表达的序列标签数据库进行了检索。结果，从人肺cDNA文库中分离出cDNA克隆。该基因被命名为C6orf37 (Chromosorne 6 open reading frame 37)，全长约2.5 kb，由两个外显子组成，编码一个235个氨基酸的蛋白，与人类带粘连蛋白的粘蛋白样结构域具有同源性，这是一种具有精子透明带结合活性的精子多结构域跨膜蛋白。出乎意料的是，RT-PCR分析检测到了C6orf37位点反义DNA链的转录本。这些反义转录本所代表的C6orf370S （C6orf37 Opposite Strand）基因不含开放阅读框。在许多组织中观察到C6orf37和C6orf370S的转录本，在肺、肾和睾丸中表达最丰富。综上所述，特别是C6orf37和C6orf370S在肺中的丰富表达，表明C6orf37和C6orf370S是DPB的优秀候选基因。
Diffuse panbronchiolitis (DPB) is an unusual form of bronchiolar disease affecting exclusively East Asians. Strong associations of DPB with the class I human leukocyte anticens 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 (Chromosorne 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 C6orf370S (C6orf37 Opposite Strand) and represented by these anti-sense transcripts contained no open reading frame. The transcripts from C6orf37 and C6orf370S 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 C6orf370S are excellent candidate genes for DPB.