Le Thu H, Christensen Ole F, Nielsen Bjarne, Sahana Goutam
Department of Molecular Biology and Genetics, Center for Quantitative Genetics and Genomics, Aarhus University, Tjele, Denmark.
Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences, Uppsala, Sweden.
Genet Sel Evol. 2017 Jan 24;49(1):12. doi: 10.1186/s12711-017-0289-2.
Selection for sound conformation has been widely used as a primary approach to reduce lameness and leg weakness in pigs. Identification of genomic regions that affect conformation traits would help to improve selection accuracy for these lowly to moderately heritable traits. Our objective was to identify genetic factors that underlie leg and back conformation traits in three Danish pig breeds by performing a genome-wide association study followed by meta-analyses.
Data on four conformation traits (front leg, back, hind leg and overall conformation) for three Danish pig breeds (23,898 Landrace, 24,130 Yorkshire and 16,524 Duroc pigs) were used for association analyses. Estimated effects of single nucleotide polymorphisms (SNPs) from single-trait association analyses were combined in two meta-analyses: (1) a within-breed meta-analysis for multiple traits to examine if there are pleiotropic genetic variants within a breed; and (2) an across-breed meta-analysis for a single trait to examine if the same quantitative trait loci (QTL) segregate across breeds. SNP annotation was implemented through Sus scrofa Build 10.2 on Ensembl to search for candidate genes.
Among the 14, 12 and 13 QTL that were detected in the single-trait association analyses for the three breeds, the most significant SNPs explained 2, 2.3 and 11.4% of genetic variance for back quality in Landrace, overall conformation in Yorkshire and back quality in Duroc, respectively. Several candidate genes for these QTL were also identified, i.e. LRPPRC, WRAP73, VRTN and PPARD likely control conformation traits through the regulation of bone and muscle development, and IGF2BP2, GH1, CCND2 and MSH2 can have an influence through growth-related processes. Meta-analyses not only confirmed many significant SNPs from single-trait analyses with higher significance levels, but also detected several additional associated SNPs and suggested QTL with possible pleiotropic effects.
Our results imply that conformation traits are complex and may be partly controlled by genes that are involved in bone and skeleton development, muscle and fat metabolism, and growth processes. A reliable list of QTL and candidate genes was provided that can be used in fine-mapping and marker assisted selection to improve conformation traits in pigs.
选择优良体型一直被广泛用作减少猪跛行和腿部虚弱的主要方法。识别影响体型性状的基因组区域将有助于提高这些低至中度遗传力性状的选择准确性。我们的目标是通过进行全基因组关联研究并随后进行荟萃分析，来识别三个丹麦猪品种腿部和背部体型性状的遗传因素。
使用三个丹麦猪品种（23898头长白猪、24130头大白猪和16524头杜洛克猪）的四个体型性状（前腿、背部、后腿和整体体型）数据进行关联分析。单性状关联分析中单个核苷酸多态性（SNP）的估计效应在两项荟萃分析中进行合并：（1）针对多个性状的品种内荟萃分析，以检查一个品种内是否存在多效性遗传变异；（2）针对单个性状的品种间荟萃分析，以检查相同的数量性状位点（QTL）是否在不同品种间分离。通过Ensembl上的猪10.2版本进行SNP注释，以寻找候选基因。
在三个品种的单性状关联分析中检测到的14个、12个和13个QTL中，最显著的SNP分别解释了长白猪背部质量、大白猪整体体型和杜洛克猪背部质量遗传变异的2%、2.3%和11.4%。还鉴定了这些QTL的几个候选基因，即LRPPRC、WRAP73、VRTN和PPARD可能通过调节骨骼和肌肉发育来控制体型性状，而IGF2BP2、GH1、CCND2和MSH2可能通过与生长相关的过程产生影响。荟萃分析不仅证实了单性状分析中的许多显著SNP，且显著性水平更高，还检测到了几个额外的相关SNP，并提出了可能具有多效性效应的QTL。
我们的结果表明，体型性状很复杂，可能部分由参与骨骼发育、肌肉和脂肪代谢以及生长过程的基因控制。提供了一份可靠的QTL和候选基因列表，可用于精细定位和标记辅助选择，以改善猪的体型性状。
