Fine mapping of a swine quantitative trait locus for number of vertebrae and analysis of an orphan nuclear receptor, germ cell nuclear factor (NR6A1)

Abstract

The number of vertebrae in pigs varies and is associated with meat productivity. Wild boars, which are ancestors of domestic pigs, have 19 vertebrae. In comparison, European commercial breeds have 21-23 vertebrae, probably owing to selective breeding for enlargement of body size. We previously identified two quantitative trait loci (QTL) for the number of vertebrae on Sus scrofa chromosomes (SSC) 1 and 7. These QTL explained an increase of more than two vertebrae. Here, we performed a map-based study to define the QTL region on SSC1. By using three F 2 experimental families, we performed interval mapping and recombination analyses and defined the QTL within a 1.9-cM interval. Then we analyzed the linkage disequilibrium of microsatellite markers in this interval and found that 10 adjacent markers in a 300-kb region were almost fixed in European commercial breeds. Genetic variation of the markers was observed in Asian local breeds or wild boars. This region encoded an orphan nuclear receptor, germ cell nuclear factor (NR6A1, formerly known as GCNF), which contained an amino acid substitution (Pro192Leu) coincident with the QTL. This substitution altered the binding activity of NR6A1 to its corepressors, nuclear receptor-associated protein 80 (RAP80) and nuclear receptor corepressor 1 (NCOR1). In addition, somites of mouse embryos demonstrated expression of NR6A1 protein. Together, these results suggest that NR6A1 is a strong candidate for one of the QTL that influence number of vertebrae in pigs.

Strong signatures of selection in the domestic pig genome

“…1E). For one of these (NR6A1), a strong candidate mutation (Pro192Leu) has already been proposed (14), and the results of the present study support this hypothesis. Further work is required to reveal the causative mutations associated with the PLAG1 and LCORL loci.…”

“…1C). This region harbors a major QTL affecting the numbers of vertebrae in pigs, and a missense mutation in NR6A1 has been proposed to be causative (14). Two of the other convincing selective sweep candidates overlapped major QTLs for body length in our intercross between Large White pigs and wild boar (15,16).…”

MC1R, KIT, IGF2, and NR6A1 as markers for genetic differentiation in Thai native, wild boars, and Duroc and Chinese Meishan pigs

“…Variations in rib and vertebrae numbers usually influence body size, carcass length, and teat number in pigs (Mikawa et al, 2007;Duijvesteijn et al, 2014). Native pigs and wild boar have 19 vertebrae, whereas European commercial breeds for pig production have 20 to 23 vertebrae; this is due to selection for intensive pig production, which has increased the number of teats and litter size in pigs (Rubin et al, 2012;Duijvesteijn et al, 2014).…”

Investigation of a Short Interspersed Nuclear Element Polymorphic Site in the PorcineVertninGene: Allele Frequencies and Association Study With Meat Quality, Carcass and Production Traits in Italian Large White pigs

“…Other studies identified QTL for vertebral number on SSC1 and SSC7 (Wada et al, 2000;Sato et al, 2003;Mikawa et al, 2005). Mikawa et al (2007) showed that a missense mutation in the nuclear receptor subfamily 6, group A, member 1 (NR6A1) gene is the most probable causative mutation for the QTL on SSC1. This mutation is fixed for the allele associated with larger number of thoracic and lumbar vertebrae in most commercial pig breeds (Mikawa et al, 2007;Yang et al, 2009;Ruben et al, 2012), including Italian Large White (Fontanesi et al, manuscript in preparation).…”