Single Nucleotide Polymorphisms of NUCB2 and Their Genetic Associations with Milk Production Traits in Dairy Cows
Single Nucleotide Polymorphisms of NUCB2 and Their Genetic Associations with Milk Production Traits in Dairy Cows
复制标题
NUCB2单核苷酸多态性及其与奶牛产奶性状的遗传关联
DOI：
10.3390/genes10060449
复制
发表时间：
2019-06-01
期刊：
影响因子：
3.5
通讯作者：
Sun, Dongxiao
中科院分区：
文献类型：
--
作者：
Han, Bo;Yuan, Yuwei;Sun, Dongxiao
我们之前利用RNA测序技术检测了中国荷斯坦奶牛在泌乳期、泌乳早期和泌乳高峰期的肝脏转录组，结果表明核结合蛋白2 （NUCB2）基因在泌乳早期和泌乳高峰期的表达量较干期显著增加（q值< 0.05），可能与泌乳性状有关。因此，在本研究中，我们检测了NUCB2的单核苷酸多态性（snp），并分析了它们与产奶量、脂肪量、脂肪率、蛋白质产量和蛋白质百分比的遗传相关性。我们对NUCB2的5′和3′侧翼区进行了全编码和2000 bp的测序，鉴定出10个snp，其中5′侧翼区1个，3′未翻译区（UTR） 2个，3′侧翼区7个。单snp关联分析结果显示，10个snp与泌乳第一次或第二次泌乳产奶量、脂肪量、脂肪率、蛋白质产量或蛋白质百分比显著相关（p值<= 1 × 10−4和0.05）。此外，我们利用Haploview 4.2估计了10个snp的连锁不平衡（LD），发现这些snp在一个单倍型区域高度连锁（D′= 0.98 ~ 1.00），并且该区域在两次哺乳中至少与一种乳性状显著相关（p值：0.0002 ~ 0.047）。进一步，我们预测了NUCB2 5′侧区snp引起的转录因子结合位点（TFBSs）的变化，并认为g.35735477C>T可能通过改变ETS转录因子3 （ELF3）、尾型同源盒2 （CDX2）、哺乳动物c型LTR TATA盒（VTATA）、活化T细胞核因子（NFAT）和v-ets红母细胞病病毒E26癌基因同源物（ERG）的TFBSs影响NUCB2的表达（基质相似阈值，MST > 0.85）。然而，NUCB2基因的调控机制及其多态性对乳性状的影响还有待进一步研究。本研究结果首次揭示了NUCB2基因对奶牛乳质性状的遗传影响，并提示该显著snp可用于基因组选择，以提高奶牛育种选择的准确性。
We previously used the RNA sequencing technique to detect the hepatic transcriptome of Chinese Holstein cows among the dry period, early lactation, and peak of lactation, and implied that the nucleobindin 2 (NUCB2) gene might be associated with milk production traits due to its expression being significantly increased in early lactation or peak of lactation as compared to dry period (q value < 0.05). Hence, in this study, we detected the single nucleotide polymorphisms (SNPs) of NUCB2 and analyzed their genetic associations with milk yield, fat yield, fat percentage, protein yield, and protein percentage. We re-sequenced the entire coding and 2000 bp of 5′ and 3′ flanking regions of NUCB2 by pooled sequencing, and identified ten SNPs, including one in 5′ flanking region, two in 3′ untranslated region (UTR), and seven in 3′ flanking region. The single-SNP association analysis results showed that the ten SNPs were significantly associated with milk yield, fat yield, fat percentage, protein yield, or protein percentage in the first or second lactation (p values <= 1 × 10−4 and 0.05). In addition, we estimated the linkage disequilibrium (LD) of the ten SNPs by Haploview 4.2, and found that the SNPs were highly linked in one haplotype block (D′ = 0.98–1.00), and the block was also significantly associated with at least one milk traits in the two lactations (p values: 0.0002–0.047). Further, we predicted the changes of transcription factor binding sites (TFBSs) that are caused by the SNPs in the 5′ flanking region of NUCB2, and considered that g.35735477C>T might affect the expression of NUCB2 by changing the TFBSs for ETS transcription factor 3 (ELF3), caudal type homeobox 2 (CDX2), mammalian C-type LTR TATA box (VTATA), nuclear factor of activated T-cells (NFAT), and v-ets erythroblastosis virus E26 oncogene homolog (ERG) (matrix similarity threshold, MST > 0.85). However, the further study should be performed to verify the regulatory mechanisms of NUCB2 and its polymorphisms on milk traits. Our findings first revealed the genetic effects of NUCB2 on the milk traits in dairy cows, and suggested that the significant SNPs could be used in genomic selection to improve the accuracy of selection for dairy cattle breeding.