Characterisation of five candidate genes within the ETEC F4ab/ac candidate region in pigs.
Characterisation of five candidate genes within the ETEC F4ab/ac candidate region in pigs.
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DOI：
10.1186/1756-0500-4-225
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发表时间：
2011-06-30
影响因子：
1.8
通讯作者：
Jørgensen CB
中科院分区：
文献类型：
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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
产肠毒素大肠杆菌(ETEC)表达F4ab和F4ac菌毛，是导致养猪业腹泻暴发的主要原因，可感染新生仔猪和断奶仔猪。一些猪对这种感染具有抵抗力，易感性是孟德尔遗传的一种简单显性特征。确定这一特征背后的遗传学将为猪的福利和养猪业带来极大的好处，因为它提供了一个机会，可以选择对遗传敏感的动物，从而减少腹泻暴发的数量。最近通过单倍型共享将该性状定位到猪13号染色体上的2.5Mb区域，该区域包含18个注释基因。5个ETEC F4ab/ac易感基因(TFRC、AcK1、MUC20、MUC4和KIAA0226)的编码区均位于2.5Mb区域，以确定是否存在可能的致病突变。在编码区或其两侧的内含子上共检测到34个多态性。其中两个的基因分型数据与ETEC F4ab/ac基因座、TFRC内含子11的G-C多态和KIAA0226外显子22的C-T沉默多态完全匹配。在包括各种肠道组织的猪组织小组中，研究了这五个基因的转录图谱。这5个基因在肠道组织中均有不同程度的表达，但在ETEC F4ab/Ac抗性动物和ETEC F4ab/Ac敏感动物之间均未发现差异表达。这些已发现的多态性都不是ETEC F4ab/Ac易感性的明显原因突变，因为它们不会影响总的mRNA表达水平，也不会影响氨基酸组成。然而，我们不能排除这5个基因是ETEC F4ab/ac感染的真正候选基因，因为已发现的多态性可能影响翻译机构，可能存在替代剪接形式，翻译后机制可能有助于疾病易感性。
Enterotoxigenic Escherichia coli (ETEC) that express the F4ab and F4ac fimbriae is a major contributor to diarrhoea outbreaks in the pig breeding industry, infecting both newborn and weaned piglets. Some pigs are resistant to this infection, and susceptibility is inherited as a simple dominant Mendelian trait. Indentifying the genetics behind this trait will greatly benefit pig welfare as well as the pig breeding industry by providing an opportunity to select against genetically susceptible animals, thereby reducing the number of diarrhoea outbreaks. The trait has recently been mapped by haplotype sharing to a 2.5 Mb region on pig chromosome 13, a region containing 18 annotated genes. The coding regions of five candidate genes for susceptibility to ETEC F4ab/ac infection (TFRC, ACK1, MUC20, MUC4 and KIAA0226), all located in the 2.5 Mb region, were investigated for the presence of possible causative mutations. A total of 34 polymorphisms were identified in either coding regions or their flanking introns. The genotyping data for two of those were found to perfectly match the genotypes at the ETEC F4ab/ac locus, a G to C polymorphism in intron 11 of TFRC and a C to T silent polymorphism in exon 22 of KIAA0226. Transcriptional profiles of the five genes were investigated in a porcine tissue panel including various intestinal tissues. All five genes were expressed in intestinal tissues at different levels but none of the genes were found differentially expressed between ETEC F4ab/ac resistant and ETEC F4ab/ac susceptible animals in any of the tested tissues. None of the identified polymorphisms are obvious causative mutations for ETEC F4ab/ac susceptibility, as they have no impact on the level of the overall mRNA expression nor predicted to influence the composition of the amino acids composition. However, we cannot exclude that the five tested genes are bona fide candidate genes for susceptibility to ETEC F4ab/ac infection since the identified polymorphism might affect the translational apparatus, alternative splice forms may exist and post translational mechanisms might contribute to disease susceptibility.