Biostatistics Group, Department of Genetics, Wroclaw University of Environmental and Life Sciences, Kozuchowska 7, 51-631 Wroclaw, Poland.
Institute of Animal Breeding, Krakowska 1, 32-083 Balice, Poland.
Animal. 2019 Oct;13(10):2156-2163. doi: 10.1017/S1751731119000338. Epub 2019 Mar 5.
Mastitis is an inflammatory disease of the mammary gland, which has a significant economic impact and is an animal welfare concern. This work examined the association between single nucleotide polymorphisms (SNPs) and copy number variations (CNVs) with the incidence of clinical mastitis (CM). Using information from 16 half-sib pairs of Holstein-Friesian cows (32 animals in total) we searched for genomic regions that differed between a healthy (no incidence of CM) and a mastitis-prone (multiple incidences of CM) half-sib. Three cows with average sequence depth of coverage below 10 were excluded, which left 13 half-sib pairs available for comparisons. In total, 191 CNV regions were identified, which were deleted in a mastitis-prone cow, but present in its healthy half-sib and overlapped in at least nine half-sib pairs. These regions overlapped with exons of 46 genes, among which APP (BTA1), FOXL2 (BTA1), SSFA2 (BTA2), OTUD3 (BTA2), ADORA2A (BTA17), TXNRD2 (BTA17) and NDUFS6 (BTA20) have been reported to influence CM. Moreover, two duplicated CNV regions present in nine healthy individuals and absent in their mastitis-affected half-sibs overlapped with exons of a cholinergic receptor nicotinic α 10 subunit on BTA15 and a novel gene (ENSBTAG00000008519) on BTA27. One CNV region deleted in nine mastitis-affected sibs overlapped with two neighbouring long non-coding RNA sequences located on BTA12. Single nucleotide polymorphisms with differential genotypes between a healthy and a mastitis-affected sib included 17 polymorphisms with alternate alleles in eight affected and healthy half-sib families. Three of these SNPs were located introns of genes: MET (BTA04), RNF122 (BTA27) and WRN (BTA27). In summary, structural polymorphisms in form of CNVs, putatively play a role in susceptibility to CM. Specifically, sequence deletions have a greater effect on reducing resistance against mastitis, than sequence duplications have on increasing resistance against the disease.
乳腺炎是一种乳腺炎症性疾病，对经济有重大影响，也是动物福利关注的问题。本研究旨在探讨单核苷酸多态性（SNP）和拷贝数变异（CNV）与临床乳腺炎（CM）发病之间的相关性。利用荷斯坦弗里生牛 16 对半同胞（共 32 头）的信息，我们在健康（无 CM 发病）和易患 CM 的半同胞（多次 CM 发病）之间寻找基因组区域差异。排除了 3 头测序深度低于 10 的奶牛，最终有 13 对半同胞可供比较。共鉴定出 191 个 CNV 区域，这些区域在易患 CM 的奶牛中缺失，但在其健康半同胞中存在，并且至少在 9 对半同胞中重叠。这些区域与 46 个基因的外显子重叠，其中 APP（BTA1）、FOXL2（BTA1）、SSFA2（BTA2）、OTUD3（BTA2）、ADORA2A（BTA17）、TXNRD2（BTA17）和 NDUFS6（BTA20）已被报道影响 CM。此外，9 个健康个体中存在的两个重复 CNV 区域而在其受 CM 影响的半同胞中不存在，这些区域与 BTA15 上的胆碱能受体烟碱 α10 亚单位和 BTA27 上的一个新基因（ENSBTAG00000008519）的外显子重叠。9 个受 CM 影响的同胞中缺失的一个 CNV 区域与位于 BTA12 上的两个相邻长非编码 RNA 序列重叠。在健康和受 CM 影响的同胞之间存在不同基因型的单核苷酸多态性，包括 8 个受影响和健康半同胞家族中 17 个具有替代等位基因的多态性。其中 3 个 SNP 位于基因的内含子：MET（BTA04）、RNF122（BTA27）和 WRN（BTA27）。总之，结构多态性以 CNV 的形式，可能在 CM 易感性中起作用。具体而言，序列缺失对降低对乳腺炎的抵抗力有更大的影响，而序列重复对增加对该疾病的抵抗力有更大的影响。
