DNA sequence polymorphisms within the bovine guanine nucleotide-binding protein Gs subunit alpha (Gsα)-encoding (GNAS) genomic imprinting domain are associated with performance traits

Abstract

BackgroundGenes which are epigenetically regulated via genomic imprinting can be potential targets for artificial selection during animal breeding. Indeed, imprinted loci have been shown to underlie some important quantitative traits in domestic mammals, most notably muscle mass and fat deposition. In this candidate gene study, we have identified novel associations between six validated single nucleotide polymorphisms (SNPs) spanning a 97.6 kb region within the bovine guanine nucleotide-binding protein Gs subunit alpha gene (GNAS) domain on bovine chromosome 13 and genetic merit for a range of performance traits in 848 progeny-tested Holstein-Friesian sires. The mammalian GNAS domain consists of a number of reciprocally-imprinted, alternatively-spliced genes which can play a major role in growth, development and disease in mice and humans. Based on the current annotation of the bovine GNAS domain, four of the SNPs analysed (rs43101491, rs43101493, rs43101485 and rs43101486) were located upstream of the GNAS gene, while one SNP (rs41694646) was located in the second intron of the GNAS gene. The final SNP (rs41694656) was located in the first exon of transcripts encoding the putative bovine neuroendocrine-specific protein NESP55, resulting in an aspartic acid-to-asparagine amino acid substitution at amino acid position 192.ResultsSNP genotype-phenotype association analyses indicate that the single intronic GNAS SNP (rs41694646) is associated (P ≤ 0.05) with a range of performance traits including milk yield, milk protein yield, the content of fat and protein in milk, culled cow carcass weight and progeny carcass conformation, measures of animal body size, direct calving difficulty (i.e. difficulty in calving due to the size of the calf) and gestation length. Association (P ≤ 0.01) with direct calving difficulty (i.e. due to calf size) and maternal calving difficulty (i.e. due to the maternal pelvic width size) was also observed at the rs43101491 SNP. Following adjustment for multiple-testing, significant association (q ≤ 0.05) remained between the rs41694646 SNP and four traits (animal stature, body depth, direct calving difficulty and milk yield) only. Notably, the single SNP in the bovine NESP55 gene (rs41694656) was associated (P ≤ 0.01) with somatic cell count--an often-cited indicator of resistance to mastitis and overall health status of the mammary system--and previous studies have demonstrated that the chromosomal region to where the GNAS domain maps underlies an important quantitative trait locus for this trait. This association, however, was not significant after adjustment for multiple testing. The three remaining SNPs assayed were not associated with any of the performance traits analysed in this study. Analysis of all pairwise linkage disequilibrium (r2) values suggests that most allele substitution effects for the assayed SNPs observed are independent. Finally, the polymorphic coding SNP in the putative bovine NESP55 gene was used to test the imprinting status of this gene across a range of foetal bov...

Alternative parameterizations of relatedness in whole genome association analysis of pre-weaning traits of Nelore-Angus calves

“…These did not overlap with most markers previously detected as associated with gestation length (Maltecca et al , 2009; 2011) in dairy cattle, although Maltecca et al (2011) identified 6 SNP on BTA3. Some SNP in imprinted domain regions on BTA13 were associated with calving difficulty and gestation length of dairy cows (Sikora et al , 2011). A similar region was identified on BTA21 (beginning at BTA21:68.1 Mb; Magee et al , 2010) including delta-like 1 homolog DLK1 and deiodinase, iodothyronine, type III ( DIO3 ); this region was associated with various traits in dairy cattle, including gestation length (Magee et al , 2011).…”

Lack of the Associations of the Polymorphisms in IGF2, MC4R and GNAS Genes with Reproduction Traits in Pigs and Imprinting Analysis of IGF2 Gene in Ovary and Cornus Uteri

“…In cattle, two SNPs in GNAS complex locus have been associated with reproductive traits (Sikora et al. ). One of them was associated with direct calving difficulty due to the size of offspring and gestation length, while the other with maternal calving difficulty (Sikora et al.…”

“…; Khatib ; Sikora et al. ). Recently, paternal imprinting of NESP55 – one of the GNAS transcripts – was confirmed in pigs (Oczkowicz et al.…”

“…Moreover, recent study on polymorphisms within GNAS complex locus revealed significant associations with carcass traits, milk yield and reproductive traits in cattle (Sikora et al. ).…”

Comparative epigenetics: relevance to the regulation of production and health traits in cattle

“…Furthermore, bovine imprinted gene orthologs have now been comprehensively shown to regulate economically important production traits in cattle (Magee et al 2010a,b;Sikora et al 2011). However, although similar epigenetic regulatory mechanisms also may affect health traits (Chao & D'Amore 2008) and exciting results are emerging in other species, the stability, heritability and association between epigenetic marks in immune genes and health traits in cattle have yet to be conclusively established.…”