The LCORL Locus is under Selection in Large-Sized Pakistani Goat Breeds

Abstract

Goat domestication and human selection for valued traits have formed diverse breeds with characteristic phenotypes. This process led to the fixation of causative genetic variants controlling breed-specific traits within regions of reduced genetic diversity-so-called "selection signatures". We previously reported an analysis of selection signatures based on pooled whole-genome sequencing data of 20 goat breeds and bezoar goats. In the present study, we reanalyzed the data and focused on a subset of eight Pakistani goat breeds (Angora, Barbari, Beetal, Dera Din Panah, Kamori, Nachi, Pahari, Teddy). We identified 749 selection signatures based on reduced heterozygosity in these breeds. A search for signatures that are shared across large-sized goat breeds revealed that five medium-to-large-sized Pakistani goat breeds had a common selection signature on chromosome 6 in a region harboring the LCORL gene, which has been shown to modulate height or body size in several mammalian species. Fine-mapping of the region confirmed that all five goat breeds with the selection signature were nearly fixed for the same haplotype in a ~191 kb region spanning positions 37,747,447-37,938,449. From the pool sequencing data, we identified a frame-shifting single base insertion into an isoform-specific exon of LCORL as a potential candidate causal variant mediating the size-increasing effect. If this preliminary result can be confirmed in independent replication studies, genotyping of this variant might be used to improve breeding programs and the selection for stature in goats.

Keywords: Capra hircus; QTL; animal breeding; body size; height; meat production; selection signature; stature; whole-genome sequence.

Figure 1

Representative animals of eight Pakistani goat breeds.

Figure 2

Manhattan plots illustrating the observed selection signatures in eight Pakistani goat breeds. Red triangles indicate 18 selection signatures that are shared between three breeds of large-sized goats (BEE, DDP, KAM). Selection signatures that harbor genes known to be related to height or body size in other species are indicated.

Figure 3

(A) Pooled heterozygosity (Hp) distribution at the LCORL locus on chromosome 6 in five medium/large-sized Pakistani goat breeds (black dots) and three small/medium breeds (grey dots). A ~191 kb region from 37,747,447 to 37,938,449 showed greatly reduced heterozygosity in the breeds with the selection signature. (B) The gene annotation for the selection signature is illustrated (NCBI annotation release 102). The genomic locations of seven genotyped variants in the LCORL gene are indicated in red (putative frameshift variant), orange (putative missense variants), or blue (silent or non-coding variants).