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

Abstract

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 F2, with additional, later generation individuals 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, divergent bi-directional selection responses for 56-day body weight in the Virginia chicken lines. To achieve this, a powerful strategy was developed to make use of data from all generations (F2-F18) of an 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 10 additional suggestive QTL for 56-day body weight were mapped, with only two of these QTL reaching genome-wide, and one suggestive, significance in analyses of the F2 generation. Five of the significant, and four of the suggestive, QTL were among the 20 loci reaching a 20% FDR-threshold in previous analyses of data from generation F15. The novel, minor-effect QTL mapped here were generally mapped due to an overall increase in power by integrating data across generations, with minor contributions from increased genome-coverage and improved marker information content. Significant and suggestive QTL now explain >60% of the difference between the parental lines, three times more than the previously reported significant QTL. Making integrated use of all available samples from multiple generations in experimental crosses is now 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-day body weight in the Virginia chicken lines.