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A SNP in intron 8 of CD46 causes a novel transcript associated with mastitis in Holsteins

文献类型： 外文期刊

作者： Wang, Xiuge 1 ; Zhong, Jifeng 1 ; Gao, Yundong 1 ; Ju, Zhihua 1 ; Huang, Jinming 1 ;

作者机构： 1.Shandong Acad Agr Sci, Dairy Cattle Res Ctr, Jinan 250131, Shandong, Peoples R China

2.Univ Missouri, Div Anim Sci, Columbia, MO 65211 USA

关键词： CD46;Alternative splicing;Functional SNP;Cattle;Mini-gene system

期刊名称：BMC GENOMICS （ 影响因子：3.969； 五年影响因子：4.478 ）

ISSN： 1471-2164

年卷期： 2014 年 15 卷

页码：

收录情况： SCI

摘要： Background: The membrane protein CD46, a ubiquitous cell surface pathogen receptor, can bind Streptococcus to trigger cell autophagy, which is a critical step in the control of infection. Results: In this study, we found a new splice variant designated CD46 transcript variant (CD46-TV). The splice variant is characterized by the retention of a 48 bp sequence from intron 8 of the bovine CD46 gene, which encodes a putative protein enlarged by 16 amino acids. CD46-TV mRNA was found to be over expressed in mastitis-infected mammary gland tissues relative to healthy tissues. A single nucleotide polymorphism (c. 1033 + 2184 C > T) in the exonic splicing enhancer (ESE) motif region was shown to result in the CD46-TV aberrant splice variant through constructing alternative alleles using the pSPL3 exon capturing vector and transfecting these into 293 T cells. Allelic frequency in 56,682 individuals belonging to 112 Bos taurus, Bos indicus, Bos javanicus, Bos grunniens and Bos mutus, etc. suggests that the C allele (80.09%) is the ancestral allele. Association analysis found that the mean genomic estimated breeding values (gEBV) for milk somatic cell score and the occurrence of clinical mastitis, as well as the milk somatic cell score of Chinese Holsteins with the CT genotype was lower than those of individuals with either the CC or TT genotypes. The mean gEBV for udder health synthesis for the TT genotype was greater than those for the CC or CT genotypes. Conclusions: Our findings suggest that the CD46 gene likely plays a critical role in the risk of mastitis caused by Streptococcus in dairy cows via an alternative splicing mechanism caused by a functional mutation in intron 8. Our data also underline the importance of variation within ESEs in regulating transcript processing.

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