Association of novel single-nucleotide polymorphisms of the vascular endothelial growth factor-A gene with high-altitude adaptation in yak (Bos grunniens).
Association of novel single-nucleotide polymorphisms of the vascular endothelial growth factor-A gene with high-altitude adaptation in yak (Bos grunniens).
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DOI：
10.4238/2013.november.18.1
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发表时间：
2013-11
期刊：
影响因子：
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通讯作者：
X. Wu;C. Liang;X. Ding;X. Guo;P. Bao;M. Chu;W. B. Liu;P. Yan
中科院分区：
文献类型：
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作者：
X. Wu;C. Liang;X. Ding;X. Guo;P. Bao;M. Chu;W. B. Liu;P. Yan
血管内皮生长因子-A基因（VEGF-A）是血管生成的关键调节因子，也是内皮细胞有丝分裂原，在高原适应中起重要作用。本研究采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）和DNA测序技术，对甘南牦牛（GN）、大通牦牛（DT）和天祝白色牦牛（TZW）3个牦牛品种的700个个体进行遗传变异筛查，发现了2个新的VEGF-A单核苷酸多态性（SNPs）。在青藏高原，GN牦牛和DT牦牛生活在高海拔地区，TZW牦牛生活在低海拔地区。SNP g.8430T>C位于VEGF-A的内含子4。SNP g.14853G>A位于VEGF-A的3'非翻译区。GN牦牛和DT牦牛的GA、AA基因型和SNP g.14853G>A等位基因频率均显著高于TZW牦牛（P < 0.01）。与TZW牦牛相比，GN牦牛和DT牦牛的TA单倍型频率极显著地高于TZW牦牛（P <0.01），而TG单倍型频率极显著地低于TZW牦牛（P < 0.01）。这2个SNPs在GN和DT牦牛中处于中度连锁不平衡，而在TZW牦牛中不存在。固定指数（FST）的成对值之间的品种研究存在显着差异。中性检验结果表明，这两个SNP之间的区域可能受到了正向选择或平衡选择，高原低氧环境可能是选择的主要决定因素。这些结果表明VEGF-A可能与牦牛的高原适应性有关。
Vascular endothelial growth factor-A gene (VEGF-A) is a key regulator of angiogenesis and an endothelial cell mitogen that plays an important role in high-altitude adaptation. In this study, we detected 2 novel single-nucleotide polymorphisms (SNPs) of VEGF-A by screening for genetic variation in 700 individuals of 3 domestic Chinese yak breeds--namely Gannan (GN), Datong (DT), and Tianzhu white (TZW)--using polymerase chain reaction-restriction fragment length polymorphism and DNA sequencing techniques. GN and DT yaks live at high altitude and TZW yaks live at low altitude on the Qinghai-Tibetan Plateau. SNP g.8430T>C is located in intron 4 of VEGF-A. SNP g.14853G>A is located in the 3' untranslated region of VEGF-A. Frequencies of the GA and AA genotypes and the A allele of SNP g.14853G>A observed in GN and DT yaks were significantly higher than that in TZW yaks (P C. The frequency of haplotype TA was significantly higher (P < 0.01), whereas the frequency of TG (P < 0.01) was significantly lower in GN and DT yaks compared with that in TZW yaks. The 2 SNPs were in moderate linkage disequilibrium in GN and DT yaks, but not in TZW yaks. The fixation index (FST) pairwise value was significantly different among the breeds studied. The neutral test result indicated that the region between the 2 SNPs may have been subjected to positive or balancing selection, and the high-altitude hypoxia environment might be the main determinant for selection. These results suggest that VEGF-A might contribute to the high-altitude adaptability of yak.