Susceptibility towards enterotoxigenic Escherichia coli F4ac diarrhea is governed by the MUC13 gene in pigs.
Susceptibility towards enterotoxigenic Escherichia coli F4ac diarrhea is governed by the MUC13 gene in pigs.
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猪对产肠毒素大肠杆菌 F4ac 腹泻的易感性由 MUC13 基因控制
DOI：
10.1371/journal.pone.0044573
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Huang L
中科院分区：
文献类型：
--
作者：
Ren J;Yan X;Ai H;Zhang Z;Huang X;Ouyang J;Yang M;Yang H;Han P;Zeng W;Chen Y;Guo Y;Xiao S;Ding N;Huang L
产肠毒素大肠杆菌（ETEC）F4 ac是新生猪和幼猪腹泻和死亡的主要决定因素。对ETEC F4 ac的敏感性由细菌特异性肠道受体控制，并作为单基因显性性状遗传。为了确定受体基因（F4 acR），我们首先使用194个微卫星标记的基因组扫描将该基因定位到猪13号染色体上的7.8 cM区域。用13号染色体上的高密度标记进一步扫描，将基因座精确到5.7 cM间隔。突变断点分析确定了2.3-Mb区域内的基因座。使用39，720个信息性SNP的进一步全基因组作图显示，最显著的标记接近2.3 Mb区域中的MUC 13基因。在一系列不同远交群体中的关联研究强烈支持MUC 13是最有可能的责任基因。我们表征了猪MUC 13基因，其编码两种转录物：MUC 13 A和MUC 13 B。这两种转录物都具有粘蛋白的特征PTS区域，其富含不同的串联重复序列。推测MUC 13 B是高度O-糖基化的，形成细菌的结合位点;而MUC 13 A不具有O-糖基化结合位点。一致地，不同品种的127头MUC 13 A纯合子独立猪均对ETEC F4 ac具有抗性，并且来自大品种组的所有718头易感动物均携带至少一个MUC 13 B等位基因。总之，我们得出结论，猪对ETEC F4 ac的易感性由MUC 13基因控制。这一发现立即转化为育种实践，因为它使我们能够建立一个有效和准确的诊断测试，以选择对易感动物。此外，这一发现提高了我们对粘蛋白的理解，粘蛋白在防御肠道病原体中起着关键作用。它首次揭示了MUC 13和肠道细菌之间的直接相互作用，这在哺乳动物中知之甚少。
Enterotoxigenic Escherichia coli (ETEC) F4ac is a major determinant of diarrhea and mortality in neonatal and young pigs. Susceptibility to ETEC F4ac is governed by the intestinal receptor specific for the bacterium and is inherited as a monogenic dominant trait. To identify the receptor gene (F4acR), we first mapped the locus to a 7.8-cM region on pig chromosome 13 using a genome scan with 194 microsatellite markers. A further scan with high density markers on chromosome 13 refined the locus to a 5.7-cM interval. Recombination breakpoint analysis defined the locus within a 2.3-Mb region. Further genome-wide mapping using 39,720 informative SNPs revealed that the most significant markers were proximal to the MUC13 gene in the 2.3-Mb region. Association studies in a collection of diverse outbred populations strongly supported that MUC13 is the most likely responsible gene. We characterized the porcine MUC13 gene that encodes two transcripts: MUC13A and MUC13B. Both transcripts have the characteristic PTS regions of mucins that are enriched in distinct tandem repeats. MUC13B is predicated to be heavily O-glycosylated, forming the binding site of the bacterium; while MUC13A does not have the O-glycosylation binding site. Concordantly, 127 independent pigs homozygous for MUC13A across diverse breeds are all resistant to ETEC F4ac, and all 718 susceptible animals from the broad breed panel carry at least one MUC13B allele. Altogether, we conclude that susceptibility towards ETEC F4ac is governed by the MUC13 gene in pigs. The finding has an immediate translation into breeding practice, as it allows us to establish an efficient and accurate diagnostic test for selecting against susceptible animals. Moreover, the finding improves our understanding of mucins that play crucial roles in defense against enteric pathogens. It revealed, for the first time, the direct interaction between MUC13 and enteric bacteria, which is poorly understood in mammals.
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影响因子：
2.4
作者：
Jacobsen, M.;Kracht, S. S.;Jorgensen, C. B.
通讯作者：
Jorgensen, C. B.
影响因子：
1.8
作者：
Jacobsen M;Cirera S;Joller D;Esteso G;Kracht SS;Edfors I;Bendixen C;Archibald AL;Vogeli P;Neuenschwander S;Bertschinger HU;Rampoldi A;Andersson L;Fredholm M;Jørgensen CB
通讯作者：
Jørgensen CB
影响因子：
14.9
作者：
Finn RD;Mistry J;Tate J;Coggill P;Heger A;Pollington JE;Gavin OL;Gunasekaran P;Ceric G;Forslund K;Holm L;Sonnhammer EL;Eddy SR;Bateman A
通讯作者：
Bateman A
DOI：
10.1158/1541-7786.mcr-10-0443
发表时间：
2011-05
期刊：
Molecular cancer research : MCR
影响因子：
--
作者：
Maher DM;Gupta BK;Nagata S;Jaggi M;Chauhan SC
通讯作者：
Chauhan SC
影响因子：
4.4
作者：
Hoorens PR;Rinaldi M;Li RW;Goddeeris B;Claerebout E;Vercruysse J;Geldhof P
通讯作者：
Geldhof P