A pig-human comparative RH map comprising 20 genes on pig chromosome 13q41 that harbours the ETEC F4ac receptor locus

A pig-human comparative RH map comprising 20 genes on pig chromosome 13q41 that harbours the ETEC F4ac receptor locus
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DOI:
10.1111/j.1439-0388.2008.00751.x
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发表时间:
2009-02-01
影响因子:
2.6
通讯作者:
Huang, L.
Huang, L.
中科院分区:
农林科学2区
文献类型:
--
作者:
Ren, J.;Tang, H.;Huang, L.

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产肠毒素大肠杆菌(ETEC) F4ac是导致新生儿和幼猪腹泻的主要原因。肠道ETEC F4ac受体(F4acR)的基因座已定位于猪染色体(SSC) 13q41,与人类染色体(HSA) 3q21和q29具有同源性。然而,致病基因和突变仍然未知。本研究的目的是对SSC13q41上的基因衍生标记进行表征,以精细定位F4acR位点,并构建高分辨率的猪-人比较图谱,以选择F4acR的候选基因。对位于HSA3q21和q29上6.8 mb区域的20个基因开发了猪特异性序列标记位点标记,其中14个标记共鉴定出34个单核苷酸多态性(snp)。18个标记被定位到SSC13q41上,另外两个标记(PLXNA1和KLF15)分别被定位到SSC13q32和SSC7q13上。结果表明,SSC7上存在一个与HSA3q21相对应的小保守片段。建立了包含18个标记的框架图谱,将SSC13q41的合成断点细化到12.3 centiRay区域。比较辐射杂交(RH)图谱揭示了人类基因组中三个有趣的F4acR候选基因,即MUC4、MUC13和MUC20。与6个标记多态性的连锁分析显示,MUC4与F4acR位点的连锁最为显著。
The enterotoxigenic Escherichia coli (ETEC) F4ac is a major cause of diarrhoea in newborn and young pigs. The locus for the intestinal ETEC F4ac receptor (F4acR) has been mapped to pig chromosome (SSC) 13q41 with known homology to human chromosome (HSA) 3q21 and q29. However, the causative gene and mutation(s) remain unknown. The aim of this study was to characterize gene-derived markers on SSC13q41 for fine mapping of the F4acR locus, and construct a high-resolution pig-human comparative map to select positional candidate genes for F4acR. Pig-specific sequence-tagged site markers were developed for 20 genes that are located in a 6.8-Mb region on HSA3q21 and q29, and a total of 34 single-nucleotide polymorphisms (SNPs) were identified in 14 of 20 markers developed. Eighteen markers were mapped to SSC13q41, while the other two markers (PLXNA1 and KLF15) were assigned to SSC13q32 and SSC7q13, respectively, by radiation hybrid mapping. This result showed that there was a small conserved segment on SSC7 corresponding to HSA3q21. A framework map comprising 18 markers on SSC13q41 was established, refining the synteny breakpoint on SSC13q41 to a region of 12.3 centiRay. The comparative radiation hybrid (RH) map revealed three interesting candidate genes for F4acR from the human genome, viz. MUC4, MUC13 and MUC20. Linkage analysis with six marker polymorphisms revealed that MUC4 had the most significant linkage with the F4acR locus.