Analysis of porcine body size variation using re-sequencing data of miniature and large pigs

Abstract

Background: Domestication has led to substantial phenotypic and genetic variation in domestic animals. In pigs, the size of so called minipigs differs by one order of magnitude compared to breeds of large body size. We used biallelic SNPs identified from re-sequencing data to compare various publicly available wild and domestic populations against two minipig breeds to gain better understanding of the genetic background of the extensive body size variation. We combined two complementary measures, expected heterozygosity and the composite likelihood ratio test implemented in "SweepFinder", to identify signatures of selection in Minipigs. We intersected these sweep regions with a measure of differentiation, namely F_ST, to remove regions of low variation across pigs. An extraordinary large sweep between 52 and 61 Mb on chromosome X was separately analyzed based on SNP-array data of F₂ individuals from a cross of Goettingen Minipigs and large pigs.

Results: Selective sweep analysis identified putative sweep regions for growth and subsequent gene annotation provided a comprehensive set of putative candidate genes. A long swept haplotype on chromosome X, descending from the Goettingen Minipig founders was associated with a reduction of adult body length by 3% in F₂ cross-breds.

Conclusion: The resulting set of genes in putative sweep regions implies that the genetic background of body size variation in pigs is polygenic rather than mono- or oligogenic. Identified genes suggest alterations in metabolic functions and a possible insulin resistance to contribute to miniaturization. A size QTL located within the sweep on chromosome X, with an estimated effect of 3% on body length, is comparable to the largest known in pigs or other species. The androgen receptor AR, previously known to influence pig performance and carcass traits, is the most obvious potential candidate gene within this region.

Keywords: Body size; Goettingen Minipig; Whole genome resequencing; X-chromosomal QTL.

Fig. 1

Neighbor-joining tree computed from pairwise IBS distances. Based on SNP data of the randomly selected chromosomes 1, 8 and 13 for all individuals (due to computational limitations). Asian wild boars in dark blue, Asian domestics in light blue, European wild boars in dark green, European domestics in light green, Mini-LEWE in orange and Goettingen Minipigs in red

Fig. 2

CLR test and normalized expected heterozygosity within minipigs and F_ST between large pigs and minipigs. Regions on chromosomes 2, 5, 8 and 14 identified as putative selective sweeps are highlighted; Blue rectangles underlie detected putative sweeps

Fig. 3

Large X-chromosomal sweep region, linkage decay and co-located genotypes in cross-bred animals. a Normalized expected heterozygosity in minipigs and fixation index between minipigs and European (green), South Asian (lightblued) and North Asian (darkblue) across the critical region of Chromosome X; b Haplotype breakdown within the major sweep region in all large pig breeds and in the minipig breed respectively, positions in Mb, centered at 56′716’179 Mb; c Allelic state at 8 analyzed SNPs in the sweep region between 50 and 62 Mb (red = homozygous for minipig allele, orange = hemi−/ heterozygous, beige = homozygous for opposite allele), positions in bp. Red dot and blue and grey triangles indicate SNP positions; (♀ = female, ♂ = male)

Fig. 4

Neighbor-joining tree for all markers between 52 and 61 Mb on chromosome X. Asian wild boars in dark blue, Asian domestics in light blue, European wild boars in dark green, European domestics in light green, Mini-LEWE in orange and Goettingen Minipigs in red

Fig. 5

Estimated effects of the X-chromosomal haplotype state on body size. a and b Least-square means for the significant effects for traits length and height at slaughter. c and d Violin plots of phenotypes, corrected for all significant covariates, apart from haplotype/ sex for the respective traits

Fig. 6

Overlaps between selection signature detection methods