replication and explorations of high-order epistasis using a large advanced intercross line pedigree复制和探索的高阶上位使用大型先进的交叉线的血统.pdfVIP

Replication and Explorations of High-Order Epistasis Using a Large Advanced Intercross Line Pedigree 1. 1. 2 ¨ 1,3 Mats Pettersson , Francois Besnier , Paul B. Siegel , Orjan Carlborg * 1 Department of Animal Breeding and Genetics, Swedish University of Agriculture Sciences (SLU), Uppsala, Sweden, 2 Department of Animal and Poultry Sciences, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, United States of America, 3 Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden Abstract Dissection of the genetic architecture of complex traits persists as a major challenge in biology; despite considerable efforts, much remains unclear including the role and importance of genetic interactions. This study provides empirical evidence for a strong and persistent contribution of both second- and third-order epistatic interactions to long-term selection response for body weight in two divergently selected chicken lines. We earlier reported a network of interacting loci with large effects on body weight in an F2 intercross between these high– and low–body weight lines. Here, most pair-wise interactions in the network are replicated in an independent eight-generation advanced intercross line (AIL). The original report showed an important contribution of capacitating epistasis to growth, meaning that the genotype at a hub in the network releases the effects of one or several peripheral loci. After fine-mapping of the loci in the AIL, we show that these interactions were persistent over time. The replication of five of six originally reported epistatic loci, as well as the capacitating epistasis, provides strong empirical evidence that the originally observed epistasis is of biolog