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对包含MHC III类基因的原麝袋鼠(尤金袋鼠,Macropus eugenii)直系同源基因的基因组区域的分析。

Analysis of the genomic region containing the tammar wallaby (Macropus eugenii) orthologues of MHC class III genes.

作者信息

Cross J G R, Harrison G A, Coggill P, Sims S, Beck S, Deakin J E, Graves J A Marshall

机构信息

Comparative Genomics Unit, ARC Centre for Kangaroo Genomics, Research School of Biological Sciences, Australian National University, Canberra, Australia.

出版信息

Cytogenet Genome Res. 2005;111(2):110-7. doi: 10.1159/000086379.

Abstract

Major histocompatibility complex (MHC) molecules are central to development and regulation of the immune system in all jawed vertebrates. MHC class III cytokine genes from the tumor necrosis factor core family, including tumor necrosis factor (TNF) and lymphotoxin alpha and beta (LTA, LTB), are well studied in human and mouse. Orthologues have been identified in several other eutherian species and the cDNA sequences have been reported for a model marsupial, the tammar wallaby. Comparative genomics can help to determine gene function, to understand the evolution of a gene or gene family, and to identify potential regulatory regions. We therefore cloned the genomic region containing the tammar LTB, TNF, and LTA orthologues by "genome walking", using primers designed from known tammar sequences and regions conserved in other species. We isolated two tammar BAC clones containing all three genes. These tammar genes show similar intergenic distances and the same transcriptional orientation as in human and mouse. Gene structures and sequences are also very conserved. By comparing the tammar, human and mouse genomic sequences we were able to identify candidate regulatory regions for these genes in mammals. Full length sequencing of BACs containing the three genes has been partially completed, and reveals the presence of a number of other tammar MHC III orthologues in this region.

摘要

主要组织相容性复合体(MHC)分子对于所有有颌脊椎动物免疫系统的发育和调节至关重要。来自肿瘤坏死因子核心家族的MHC III类细胞因子基因,包括肿瘤坏死因子(TNF)以及淋巴毒素α和β(LTA、LTB),在人类和小鼠中已得到充分研究。在其他几种真兽类物种中也已鉴定出直系同源物,并且已报道了一种有袋类动物模型——帚尾袋鼩的cDNA序列。比较基因组学有助于确定基因功能、理解基因或基因家族的进化以及识别潜在的调控区域。因此,我们利用从帚尾袋鼩已知序列和其他物种保守区域设计的引物,通过“基因组步移”克隆了包含帚尾袋鼩LTB、TNF和LTA直系同源物的基因组区域。我们分离出了两个包含所有这三个基因的帚尾袋鼩BAC克隆。这些帚尾袋鼩基因显示出与人类和小鼠相似的基因间距离以及相同的转录方向。基因结构和序列也非常保守。通过比较帚尾袋鼩、人类和小鼠的基因组序列,我们能够识别出这些基因在哺乳动物中的候选调控区域。包含这三个基因的BAC的全长测序已部分完成,并且揭示了该区域存在许多其他帚尾袋鼩MHC III直系同源物。

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