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Genome-wide association study of body weight in Australian Merino sheep reveals an orthologous region on OAR6 to human and bovine genomic regions affecting height and weight.

Al-Mamun HA, Kwan P, Clark SA, Ferdosi MH, Tellam R, Gondro C - Genet. Sel. Evol. (2015)

Bottom Line: One region on sheep (Ovis aries) chromosome 6 (OAR6) between 36.15 and 38.56 Mb, included 13 significant SNPs that were associated with BW; the most significant SNP was OAR6_41936490.1 (P = 2.37 × 10(-16)) at 37.69 Mb with an allele substitution effect of 2.12 kg, which corresponds to 0.248 phenotypic standard deviations for BW.The GWAS analysis detected 39 SNPs associated with BW in sheep and a major QTL region was identified on OAR6.In several other mammalian species, regions that are syntenic with this region have been found to be associated with body size traits, which may reflect that the underlying biological mechanisms share a common ancestry.

View Article: PubMed Central - PubMed

Affiliation: School of Environmental and Rural Science, University of New England, Armidale, NSW, 2351, Australia. hawlader.almamun@une.edu.au.

ABSTRACT

Background: Body weight (BW) is an important trait for meat production in sheep. Although over the past few years, numerous quantitative trait loci (QTL) have been detected for production traits in cattle, few QTL studies have been reported for sheep, with even fewer on meat production traits. Our objective was to perform a genome-wide association study (GWAS) with the medium-density Illumina Ovine SNP50 BeadChip to identify genomic regions and corresponding haplotypes associated with BW in Australian Merino sheep.

Methods: A total of 1781 Australian Merino sheep were genotyped using the medium-density Illumina Ovine SNP50 BeadChip. Among the 53 862 single nucleotide polymorphisms (SNPs) on this array, 48 640 were used to perform a GWAS using a linear mixed model approach. Genotypes were phased with hsphase; to estimate SNP haplotype effects, linkage disequilibrium blocks were identified in the detected QTL region.

Results: Thirty-nine SNPs were associated with BW at a Bonferroni-corrected genome-wide significance threshold of 1 %. One region on sheep (Ovis aries) chromosome 6 (OAR6) between 36.15 and 38.56 Mb, included 13 significant SNPs that were associated with BW; the most significant SNP was OAR6_41936490.1 (P = 2.37 × 10(-16)) at 37.69 Mb with an allele substitution effect of 2.12 kg, which corresponds to 0.248 phenotypic standard deviations for BW. The region that surrounds this association signal on OAR6 contains three genes: leucine aminopeptidase 3 (LAP3), which is involved in the processing of the oxytocin precursor; NCAPG non-SMC condensin I complex, subunit G (NCAPG), which is associated with foetal growth and carcass size in cattle; and ligand dependent nuclear receptor corepressor-like (LCORL), which is associated with height in humans and cattle.

Conclusions: The GWAS analysis detected 39 SNPs associated with BW in sheep and a major QTL region was identified on OAR6. In several other mammalian species, regions that are syntenic with this region have been found to be associated with body size traits, which may reflect that the underlying biological mechanisms share a common ancestry. These findings should facilitate the discovery of causative variants for BW and contribute to marker-assisted selection.

No MeSH data available.


Manhattan plots. Manhattan plots of genome-wide -log10 (p-values) for body weight in Australian Merino sheep. Top panel – individual SNP results; lower panel – smoothed median P-values using five SNP intervals
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Fig1: Manhattan plots. Manhattan plots of genome-wide -log10 (p-values) for body weight in Australian Merino sheep. Top panel – individual SNP results; lower panel – smoothed median P-values using five SNP intervals

Mentions: The GWAS identified one major region with a strong association with BW between 36.15 and 38.56 Mb on OAR6 (Fig. 1 top panel). To reduce the detection of spurious associations, GWAS results were smoothed with a running median of the P-values that spanned five adjacent SNPs (Fig. 1 lower panel). For SNPs with P-values less than 0.01, the quantile-quantile (Q-Q) plot revealed a large deviation from the distribution under the hypothesis, which indicated a strong association between this region and BW (Fig. 2). Significant Bonferroni-corrected genome-wide associations (P < 2.05 × 10−7) were detected for 39 SNPs [See Additional file 2: Table S2], of which 13 were located on OAR6 (Table 1). Among the five most significant SNPs, four were located on OAR6 and, out of these, the most significant was OAR6_41936490.1 (P = 2.36 × 10−16), which is located at 37.69 Mb. The other three SNPs on this chromosome were s17946.1 (P = 7.97 × 10−14) at 37.1 Mb, OAR6_41877997.1 (P = 2.49 × 10−12) at 37.64 Mb, and OAR6_41003295.1 (P = 2.4 × 10−11) at 36.81 Mb. Apart from this region on OAR6, the most significant SNP was on OAR3, i.e. OAR3_128968872.1 (P = 2.16 × 11−16) at 120.9 Mb. Four SNPs were detected on OAR14, at 23.5, 32.4, 52.2 and 57.9 Mb. The remaining significant SNPs were spread over various chromosomes [See Additional file 2: Table S2]. After smoothing, only the region between 36.15 and 38.56 Mb on OAR6 exceeded the significance threshold. In this region, there were 45 SNPs on the array, of which 30 were significantly associated with BW prior to Bonferroni correction (unadjusted p-value < 0.001).Fig. 1


Genome-wide association study of body weight in Australian Merino sheep reveals an orthologous region on OAR6 to human and bovine genomic regions affecting height and weight.

Al-Mamun HA, Kwan P, Clark SA, Ferdosi MH, Tellam R, Gondro C - Genet. Sel. Evol. (2015)

Manhattan plots. Manhattan plots of genome-wide -log10 (p-values) for body weight in Australian Merino sheep. Top panel – individual SNP results; lower panel – smoothed median P-values using five SNP intervals
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4536601&req=5

Fig1: Manhattan plots. Manhattan plots of genome-wide -log10 (p-values) for body weight in Australian Merino sheep. Top panel – individual SNP results; lower panel – smoothed median P-values using five SNP intervals
Mentions: The GWAS identified one major region with a strong association with BW between 36.15 and 38.56 Mb on OAR6 (Fig. 1 top panel). To reduce the detection of spurious associations, GWAS results were smoothed with a running median of the P-values that spanned five adjacent SNPs (Fig. 1 lower panel). For SNPs with P-values less than 0.01, the quantile-quantile (Q-Q) plot revealed a large deviation from the distribution under the hypothesis, which indicated a strong association between this region and BW (Fig. 2). Significant Bonferroni-corrected genome-wide associations (P < 2.05 × 10−7) were detected for 39 SNPs [See Additional file 2: Table S2], of which 13 were located on OAR6 (Table 1). Among the five most significant SNPs, four were located on OAR6 and, out of these, the most significant was OAR6_41936490.1 (P = 2.36 × 10−16), which is located at 37.69 Mb. The other three SNPs on this chromosome were s17946.1 (P = 7.97 × 10−14) at 37.1 Mb, OAR6_41877997.1 (P = 2.49 × 10−12) at 37.64 Mb, and OAR6_41003295.1 (P = 2.4 × 10−11) at 36.81 Mb. Apart from this region on OAR6, the most significant SNP was on OAR3, i.e. OAR3_128968872.1 (P = 2.16 × 11−16) at 120.9 Mb. Four SNPs were detected on OAR14, at 23.5, 32.4, 52.2 and 57.9 Mb. The remaining significant SNPs were spread over various chromosomes [See Additional file 2: Table S2]. After smoothing, only the region between 36.15 and 38.56 Mb on OAR6 exceeded the significance threshold. In this region, there were 45 SNPs on the array, of which 30 were significantly associated with BW prior to Bonferroni correction (unadjusted p-value < 0.001).Fig. 1

Bottom Line: One region on sheep (Ovis aries) chromosome 6 (OAR6) between 36.15 and 38.56 Mb, included 13 significant SNPs that were associated with BW; the most significant SNP was OAR6_41936490.1 (P = 2.37 × 10(-16)) at 37.69 Mb with an allele substitution effect of 2.12 kg, which corresponds to 0.248 phenotypic standard deviations for BW.The GWAS analysis detected 39 SNPs associated with BW in sheep and a major QTL region was identified on OAR6.In several other mammalian species, regions that are syntenic with this region have been found to be associated with body size traits, which may reflect that the underlying biological mechanisms share a common ancestry.

View Article: PubMed Central - PubMed

Affiliation: School of Environmental and Rural Science, University of New England, Armidale, NSW, 2351, Australia. hawlader.almamun@une.edu.au.

ABSTRACT

Background: Body weight (BW) is an important trait for meat production in sheep. Although over the past few years, numerous quantitative trait loci (QTL) have been detected for production traits in cattle, few QTL studies have been reported for sheep, with even fewer on meat production traits. Our objective was to perform a genome-wide association study (GWAS) with the medium-density Illumina Ovine SNP50 BeadChip to identify genomic regions and corresponding haplotypes associated with BW in Australian Merino sheep.

Methods: A total of 1781 Australian Merino sheep were genotyped using the medium-density Illumina Ovine SNP50 BeadChip. Among the 53 862 single nucleotide polymorphisms (SNPs) on this array, 48 640 were used to perform a GWAS using a linear mixed model approach. Genotypes were phased with hsphase; to estimate SNP haplotype effects, linkage disequilibrium blocks were identified in the detected QTL region.

Results: Thirty-nine SNPs were associated with BW at a Bonferroni-corrected genome-wide significance threshold of 1 %. One region on sheep (Ovis aries) chromosome 6 (OAR6) between 36.15 and 38.56 Mb, included 13 significant SNPs that were associated with BW; the most significant SNP was OAR6_41936490.1 (P = 2.37 × 10(-16)) at 37.69 Mb with an allele substitution effect of 2.12 kg, which corresponds to 0.248 phenotypic standard deviations for BW. The region that surrounds this association signal on OAR6 contains three genes: leucine aminopeptidase 3 (LAP3), which is involved in the processing of the oxytocin precursor; NCAPG non-SMC condensin I complex, subunit G (NCAPG), which is associated with foetal growth and carcass size in cattle; and ligand dependent nuclear receptor corepressor-like (LCORL), which is associated with height in humans and cattle.

Conclusions: The GWAS analysis detected 39 SNPs associated with BW in sheep and a major QTL region was identified on OAR6. In several other mammalian species, regions that are syntenic with this region have been found to be associated with body size traits, which may reflect that the underlying biological mechanisms share a common ancestry. These findings should facilitate the discovery of causative variants for BW and contribute to marker-assisted selection.

No MeSH data available.