Low-coverage sequencing in a deep intercross of the Virginia body weight lines provides insight to the polygenic genetic architecture of growth: novel loci revealed by increased power and improved genome-coverage

Genetic dissection of highly polygenic traits is a challenge, in part due to the power necessary to confidently identify loci with minor effects. Experimental crosses are valuable resources for mapping such traits. Traditionally, genome-wide analyses of experimental crosses have targeted major loci using data from a single generation (often the F(2)) with individuals from later generations being generated for replication and fine-mapping. Here, we aim to confidently identify minor-effect loci contributing to the highly polygenic basis of the long-term, bi-directional selection responses for 56-d body weight in the Virginia body weight chicken lines. To achieve this, a strategy was developed to make use of data from all generations (F(2)–F(18)) of the advanced intercross line, developed by crossing the low and high selected lines after 40 generations of selection. A cost-efficient low-coverage sequencing based approach was used to obtain high-confidence genotypes in 1Mb bins across 99.3% of the chicken genome for >3,300 intercross individuals. In total, 12 genome-wide significant, and 30 additional suggestive QTL reaching a 10% FDR threshold, were mapped for 56-d body weight. Only 2 of these QTL reached genome-wide significance in earlier analyses of the F(2) generation. The minor-effect QTL mapped here were generally due to an overall increase in power by integrating data across generations, with contributions from increased genome-coverage and improved marker information content. The 12 significant QTL explain >37% of the difference between the parental lines, three times more than 2 previously reported significant QTL. The 42 significant and suggestive QTL together explain >80%. Making integrated use of all available samples from multiple generations in experimental crosses are economically feasible using the low-cost, sequencing-based genotyping strategies outlined here. Our empirical results illustrate the value of this strategy for mapping novel minor-effect loci contributing to complex traits to provide a more confident, comprehensive view of the individual loci that form the genetic basis of the highly polygenic, long-term selection responses for 56-d body weight in the Virginia body weight chicken lines.