全基因组关联分析揭示主效基因及修饰基因共同作用决定中国地方猪两头乌毛色
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摘要
毛色是农业动物品种的重要特征之一；“两头乌”是我国地方猪种代表性毛色表型之一,广泛分布于我国长江中下游地区,该类猪种头颈与臀尾部皮毛通常呈黑色,其余为白色,故称”两头乌”。目前影响中国地方猪两头乌毛色表型的分子遗传基础仍不清楚。
本研究选用全黑的二花脸猪和两头乌毛色猪构建了二花脸×沙子岭猪、二花脸×巴马香猪、二花脸×通城猪和二花脸×荣昌猪4个F2资源群体,通过全基因组高通量SNP60芯片的扫描,采用全基因组关联分析(GWAS)定位两头乌毛色遗传位点。资源群体F2代个体毛色表型呈连续变化,且不符合单基因性状孟德尔遗传模式,表明两头乌毛色是多基因控制的复杂性状。经全基因组关联分析发现4个F2资源群体的毛色定位结果有着相似之处,即都在SSC5、SSC11、SSC17等染色体上检测到与两头乌毛色表型显著关联的位点,同时每个资源群体也存在若干特异性关联位点,说明不同地理类型两头乌猪种在毛色遗传位点上可能有着共同的起源,但经过长期选育遗传机理不尽相同。对4个F2资源群体合并分析后,发现在SSC11上存在一个影响效应非常显著的基因位点,临近功能已知的毛色基因EDNRB,提示EDNRB基因很可能是影响中国地方猪两头乌毛色的主效基因位点。
将EDNRB基因效应固定后再次进行GAWS分析,揭示出关联性最强的标记临近SSC17上已知的毛色基因EDN3,提示EDN3是除EDNRB主效基因外另一修饰基因位点。对EDN3基因进行深度重测序,发现一个1.6Kb的沙子岭猪共享IBD区域,鉴别到11个区别沙子岭猪和二花脸、杜洛克猪的候选因果SNPs。进一步固定EDNRB基因和EDN3基因效应,在二花脸×沙子岭猪F2资源家系中SSC5和SSC8检测到显著最关联的SNP位点,分别临近毛色基因KITLG和KIT。
本研究揭示出中国地方猪两头乌毛色受一个主效基因位点(EDNRB)和多个修饰基因位点(EDN3、KIT、KITLG等)的共同作用。推测EDNRB基因控制两头乌毛色的基本轮廓,其他基因修饰两头乌的程度及躯干黑斑的出现及大小。荣昌猪毛色表型遗传机理更为复杂,受多个遗传位点控制,涉及黑色素细胞发育3个主要信号通路多个相关基因。研究结果改变了人们对毛色质量性状往往受单基因控制的传统认识,为深入鉴别导致两头乌毛色形成的因果突变位点奠定了重要前期工作基础。
Coat color is a breed characteristic in farm animals. Two-end-black coat color is one of representative coat colors in Chinese local pigs and the pig breeds are widely distributed in middle and lower areas of the Yangtze River in China. These pigs show black heads and hips and white belt bodies. So far, the molecular and genetic basis of the two-end-black phenotype remains elusive.
In this study, four F2resource populations including Erhualian×Shaziling, Erhualian×Bamaxiang, Erhualian×Tongcheng and Erhualian×Rongchang were constructed. We genotyped all F0/F1/F2animals in these four resource populations using the porcine60K SNP chip and performed a genome-wide linkage analysis to identify the genetic loci underlying the two-end-black coat color. The phenotypes of F2animals showed continuous variation and were not consistent with the monogenic Mendelian inheritance, indicating that the two-end-black phenotype is a multifactorial complex trait. GWAS revealed that several significantly loci on SSC5, SSC11and SSC17were detected in all four resource populations. A meta-analysis of these resource populations identified the most significantly locus proximal to EDNRB on SSC11, suggesting that EDNRB is a major candidate locus affecting the two-end-black phenotype in pigs.
When we fix the EDNRB effect in the farther GWAS analysis, several modifier genes effects at SSC5, SSC8, SSC17were identified. Among which gene EDN3adjacent the SSC17locus showed the most significant signal. By deep sequencing the EDN3gene, we found a1.6Kb IBD region shared by all Shaziling pigs and identified11diagnostic mutations distinguishing Shaziling from Erhualian and Duroc pigs. Further analysis by fixing the EDNRB and EDN3effects, we identified two other significantly loci on SSC5and SSC8in the Erhualian×Shaziling F2resource population. The two loci were adjacent to two coat color genes KITLG and KIT, respectively.
This study showed that the two-end-black coat color is governed by a major gene (EDNRB) and several modifier genes including EDN3, KIT and KITLG. We speculate that EDNRB control the basic conformation of two-end-black coat color, and other modifer genes affect the extent of white belt and spot sizes. The genetic mechanism of Rongchang coat color is even more complex, which were involved with three major signaling pathway of melanocytes development. The results renewed our traditional understanding of coat colors as monogenic traits, and paved the load to ultimately identify the causal variants leading to the two-end-black phenotype in Chinese indigenous pigs.
本研究选用全黑的二花脸猪和两头乌毛色猪构建了二花脸×沙子岭猪、二花脸×巴马香猪、二花脸×通城猪和二花脸×荣昌猪4个F2资源群体,通过全基因组高通量SNP60芯片的扫描,采用全基因组关联分析(GWAS)定位两头乌毛色遗传位点。资源群体F2代个体毛色表型呈连续变化,且不符合单基因性状孟德尔遗传模式,表明两头乌毛色是多基因控制的复杂性状。经全基因组关联分析发现4个F2资源群体的毛色定位结果有着相似之处,即都在SSC5、SSC11、SSC17等染色体上检测到与两头乌毛色表型显著关联的位点,同时每个资源群体也存在若干特异性关联位点,说明不同地理类型两头乌猪种在毛色遗传位点上可能有着共同的起源,但经过长期选育遗传机理不尽相同。对4个F2资源群体合并分析后,发现在SSC11上存在一个影响效应非常显著的基因位点,临近功能已知的毛色基因EDNRB,提示EDNRB基因很可能是影响中国地方猪两头乌毛色的主效基因位点。
将EDNRB基因效应固定后再次进行GAWS分析,揭示出关联性最强的标记临近SSC17上已知的毛色基因EDN3,提示EDN3是除EDNRB主效基因外另一修饰基因位点。对EDN3基因进行深度重测序,发现一个1.6Kb的沙子岭猪共享IBD区域,鉴别到11个区别沙子岭猪和二花脸、杜洛克猪的候选因果SNPs。进一步固定EDNRB基因和EDN3基因效应,在二花脸×沙子岭猪F2资源家系中SSC5和SSC8检测到显著最关联的SNP位点,分别临近毛色基因KITLG和KIT。
本研究揭示出中国地方猪两头乌毛色受一个主效基因位点(EDNRB)和多个修饰基因位点(EDN3、KIT、KITLG等)的共同作用。推测EDNRB基因控制两头乌毛色的基本轮廓,其他基因修饰两头乌的程度及躯干黑斑的出现及大小。荣昌猪毛色表型遗传机理更为复杂,受多个遗传位点控制,涉及黑色素细胞发育3个主要信号通路多个相关基因。研究结果改变了人们对毛色质量性状往往受单基因控制的传统认识,为深入鉴别导致两头乌毛色形成的因果突变位点奠定了重要前期工作基础。
Coat color is a breed characteristic in farm animals. Two-end-black coat color is one of representative coat colors in Chinese local pigs and the pig breeds are widely distributed in middle and lower areas of the Yangtze River in China. These pigs show black heads and hips and white belt bodies. So far, the molecular and genetic basis of the two-end-black phenotype remains elusive.
In this study, four F2resource populations including Erhualian×Shaziling, Erhualian×Bamaxiang, Erhualian×Tongcheng and Erhualian×Rongchang were constructed. We genotyped all F0/F1/F2animals in these four resource populations using the porcine60K SNP chip and performed a genome-wide linkage analysis to identify the genetic loci underlying the two-end-black coat color. The phenotypes of F2animals showed continuous variation and were not consistent with the monogenic Mendelian inheritance, indicating that the two-end-black phenotype is a multifactorial complex trait. GWAS revealed that several significantly loci on SSC5, SSC11and SSC17were detected in all four resource populations. A meta-analysis of these resource populations identified the most significantly locus proximal to EDNRB on SSC11, suggesting that EDNRB is a major candidate locus affecting the two-end-black phenotype in pigs.
When we fix the EDNRB effect in the farther GWAS analysis, several modifier genes effects at SSC5, SSC8, SSC17were identified. Among which gene EDN3adjacent the SSC17locus showed the most significant signal. By deep sequencing the EDN3gene, we found a1.6Kb IBD region shared by all Shaziling pigs and identified11diagnostic mutations distinguishing Shaziling from Erhualian and Duroc pigs. Further analysis by fixing the EDNRB and EDN3effects, we identified two other significantly loci on SSC5and SSC8in the Erhualian×Shaziling F2resource population. The two loci were adjacent to two coat color genes KITLG and KIT, respectively.
This study showed that the two-end-black coat color is governed by a major gene (EDNRB) and several modifier genes including EDN3, KIT and KITLG. We speculate that EDNRB control the basic conformation of two-end-black coat color, and other modifer genes affect the extent of white belt and spot sizes. The genetic mechanism of Rongchang coat color is even more complex, which were involved with three major signaling pathway of melanocytes development. The results renewed our traditional understanding of coat colors as monogenic traits, and paved the load to ultimately identify the causal variants leading to the two-end-black phenotype in Chinese indigenous pigs.
引文
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