藏绵羊血红蛋白、EPAS1基因与低氧适应相关性研究  

The Association of Genes Hemoglobin and EPAS1 with Hypoxia Adaptation in the Tibetan Sheep

作　　者：朱莉 李根 孔小艳[1] 邓茗月 董新星[1] 万宝云 杨舒黎[1] 苟潇[1] ZHU Li;LI Gen;KONG Xiaoyan;DENG Mingyue;DONG Xinxing;WAN Baoyun;YANG Shuli;GOU Xiao(College of Animal Science and Technology,Yunnan Agricultural University,Kunming 650201,China;Yimen Agriculture and Animal Husbandry,Yimen 651100,China)

机构地区：[1]云南农业大学动物科学技术学院,云南昆明650201 [2]易门县农牧局,云南易门651100

出　　处：《云南农业大学学报（自然科学版）》2020年第3期436-442,518,共8页Journal of Yunnan Agricultural University:Natural Science

基　　金：国家自然基金地区项目(31460581)。

摘　　要：【目的】筛选藏绵羊血红蛋白基因和EPAS1基因的低氧正选择位点,并解析位点遗传效应,揭示两基因在藏绵羊低氧适应中的作用。【方法】以血红蛋白、EPAS1为候选基因,筛选藏绵羊的优势SNP位点,并扩大样本检测3个海拔梯度(1500、2500和3500 m)绵羊的海拔趋势位点和血液生理指标,进行基因型与血液生理指标关联分析。【结果】藏绵羊血红蛋白、EPAS1基因分别检测到6个和12个SNPs。血红蛋白6个SNPs均为同义突变,其基因频率均未呈现海拔趋势。EPAS1基因第8内含子C871T位点突变等位基因(T)频率呈现明显海拔趋势,该位点TT基因型具有增加血红蛋白含量(HGB)、红细胞平均血红蛋白含量(MCH)和血液黏稠度的遗传效应(P<0.05);通过转录因子结合位点预测,发现该突变导致GATA(造血调控因子)结合位点丢失。EPAS1基因第9外显子G1001A为非同义突变VAL352MET,但突变等位基因频率仅为0.34,此位点3种基因型与各血液生理指标之间差异均不显著(P>0.05);通过蛋白结构同源预测,未发现蛋白结构功能变化。【结论】藏绵羊EPAS1基因第8内含子C871T位点突变等位基因(T)的频率随海拔升高而升高,其TT型能显著提高血红蛋白质量浓度14.14 g/L,是藏绵羊高血红蛋白浓度的潜在关联位点。[ Purpose] To screen the hypoxic positive selection sites of hemoglobin and EPAS1 gene, and to analyze the genetic effects of these loci, revealing the role of the two genes in hypoxia adaptation in Tibetan sheep. [Method]Hemoglobin and EPAS1 were used as candidate genes to screen the dominant SNPs in Tibetan sheep, and the expanded samples were used to detect the altitudinal trend sites and blood physiological parameters in three populations of altitudinal gradients(1 500,2 500 and 3 500 m) for analyzing the association between genotypes and blood physiological indexes.[ Results] Six and twelve SNPs were respectively detected in the Tibetan sheep hemoglobin and EPAS1 genes, respectively. Those SNPs of hemoglobin were synonymous, and their gene frequencies did not show an altitudinal trend. The allele(T) frequency of the C871 T loci in the 8 th intron of EPAS1 gene showed a significant altitudinal trend. The TT genotype of this locus had a genetic effect of increasing hemoglobin content(HGB), erythrocyte mean hemoglobin content(MCH) and blood viscosity(P<0.05). This mutation resulted in loss of GATA(hematopoietic regulatory factor)binding sites based on the prediction of transcription factor binding site. The G1001 A site in the 9 th exon of EPAS1 gene was a nonsynonymous mutation VAL352 MET, but the frequency of the mutant allele was only 0.34. There was no significant association between the three genotypes and the blood physiological indexes(P>0.05), and no change in protein structure function was found through protein structure homology prediction.[Conclusion]The frequency of the allele(T) of C871 T locus in the 8 th intron of the EPAS1 gene increased with altitudes, and its TT genotype significantly increased the hemoglobin concentration(14.14 g/L) in Tibetan sheep, suggesting a potentially associated site for high hemoglobin concentration.

关 键 词：藏绵羊 血红蛋白 EPAS1 SNP 血液生理 低氧适应 

分 类 号：S826.2[农业科学—畜牧学]