Key Laboratory of Farm Animal Genetic Resources and Germplasm Innovation of Ministry of Agriculture of China, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China.
Int J Biol Sci. 2012;8(6):870-81. doi: 10.7150/ijbs.4027. Epub 2012 Jun 15.
Hematological traits, which are important indicators of immune function in animals, have been commonly examined as biomarkers of disease and disease severity in humans and animals. Genome-wide significant quantitative trait loci (QTLs) provide important information for use in breeding programs of animals such as pigs. QTLs for hematological parameters (hematological traits) have been detected in pig chromosomes, although these are often mapped by linkage analysis to large intervals making identification of the underlying mutation problematic. Single nucleotide polymorphisms (SNPs) are the common form of genetic variation among individuals and are thought to account for the majority of inherited traits. In this study, a genome-wide association study (GWAS) was performed to detect regions of association with hematological traits in a three-generation resource population produced by intercrossing Large White boars and Minzhu sows during the period from 2007 to 2011. Illumina PorcineSNP60 BeadChip technology was used to genotype each animal and seven hematological parameters were measured (hematocrit (HCT), hemoglobin (HGB), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), mean corpuscular volume (MCV), red blood cell count (RBC) and red blood cell volume distribution width (RDW)). Data were analyzed in a three step Genome-wide Rapid Association using the Mixed Model and Regression-Genomic Control (GRAMMAR-GC) method. A total of 62 genome-wide significant and three chromosome-wide significant SNPs associated with hematological parameters were detected in this GWAS. Seven and five SNPs were associated with HCT and HGB, respectively. These SNPs were all located within the region of 34.6-36.5 Mb on SSC7. Four SNPs within the region of 43.7-47.0 Mb and fifty-five SNPs within the region of 42.2-73.8 Mb on SSC8 showed significant association with MCH and MCV, respectively. At chromosome-wide significant level, one SNP at 29.2 Mb on SSC1 and two SNPs within the region of 26.0-26.2 Mb were found to be significantly associated with RBC and RDW, respectively. Many of the SNPs were located within previously reported QTL regions and appeared to narrow down the regions compared with previously described QTL intervals. In current research, a total of seven significant SNPs were found within six candidate genes SCUBE3, KDR, TDO, IGFBP7, ADAMTS3 and AFP. In addition, the KIT gene, which has been previously reported to relate to hematological parameters, was located within the region significantly associated with MCH and MCV and could be a candidate gene. These results of this study may lead to a better understanding of the molecular mechanisms of hematological parameters in pigs.
血液学特征是动物免疫功能的重要指标，已被广泛用作人类和动物疾病及疾病严重程度的生物标志物。全基因组显著数量性状位点（QTL）为猪等动物的育种计划提供了重要信息。已经在猪染色体上检测到了血液学参数（血液学特征）的 QTL，但这些 QTL 通常通过连锁分析映射到较大的区间，使得确定潜在的突变成为问题。单核苷酸多态性（SNP）是个体之间常见的遗传变异形式，被认为是大多数遗传特征的基础。在这项研究中，进行了全基因组关联研究（GWAS），以检测 2007 年至 2011 年间杂交大白猪和民猪产生的三代资源群体中与血液学特征相关的区域。使用 Illumina PorcineSNP60 BeadChip 技术对每个动物进行基因分型，并测量了 7 个血液学参数（血细胞比容（HCT）、血红蛋白（HGB）、平均红细胞血红蛋白（MCH）、平均红细胞血红蛋白浓度（MCHC）、平均红细胞体积（MCV）、红细胞计数（RBC）和红细胞体积分布宽度（RDW））。在使用混合模型和回归-基因组控制（GRAMMAR-GC）方法的三步骤全基因组快速关联分析中对数据进行了分析。在这项 GWAS 中，共检测到与血液学参数相关的 62 个全基因组显著和 3 个染色体显著 SNP。有 7 个和 5 个 SNP 分别与 HCT 和 HGB 相关。这些 SNP 均位于 SSC7 的 34.6-36.5 Mb 区域内。位于 SSC8 的 43.7-47.0 Mb 和 42.2-73.8 Mb 区域内的 4 个 SNP 和 55 个 SNP 分别与 MCH 和 MCV 显著相关。在染色体显著水平上，在 SSC1 的 29.2 Mb 处发现一个 SNP 和在 SSC1 的 26.0-26.2 Mb 区域内的两个 SNP 分别与 RBC 和 RDW 显著相关。许多 SNP 位于先前报道的 QTL 区域内，与先前描述的 QTL 区间相比，似乎缩小了区域。在当前研究中，在 6 个候选基因 SCUBE3、KDR、TDO、IGFBP7、ADAMTS3 和 AFP 内发现了总共 7 个显著 SNP。此外，先前报道与血液学参数有关的 KIT 基因位于与 MCH 和 MCV 显著相关的区域内，可能是候选基因。本研究的结果可能有助于更好地理解猪血液学参数的分子机制。
