Genetic Polymorphisms of IGF1 and IGF1R Genes and Their Effects on Growth Traits in Hulun Buir Sheep

Abstract

The identification of candidate genes and genetic variations associated with growth traits is important for sheep breeding. Insulin like growth factor 1 (IGF1) and insulin like growth factor 1 receptor (IGF1R) are well-accepted candidate genes that affect animal growth and development. The current study attempted to assess the association between IGF1 and IGF1R genetic polymorphisms and growth traits in Hulun Buir sheep. To achieve this goal, we first identified three and ten single nucleotide polymorphisms (SNPs) in exons of IGF1 and IGF1R in Hulun Buir sheep and then constructed six haplotypes of IGF1R based on linkage disequilibrium, respectively. Association studies were performed between SNPs and haplotypes of IGF1 and IGF1R with twelve growth traits in a population encompassing 229 Hulun Buir sheep using a general linear model. Our result indicated three SNPs in IGF1 were significantly associated with four growth traits (p < 0.05). In IGF1R, three SNPs and two haplotype blocks were significantly associated with twelve growth traits (p < 0.05). The combined haplotype H5H5 and H5H6 in IGF1R showed the strong association with 12 superior growth traits in Hulun Buir sheep (p < 0.05). In conclusion, we identified SNPs and haplotype combinations associated with the growth traits, which provided genetic resources for marker-assisted selection (MAS) in Hulun Buir sheep breeding.

Keywords: Chinese indigenous sheep; IGF1; IGF1R; association analysis; growth traits; haplotype.

Figure 1

The sequencing peaks for three SNP loci of the IGF1 gene in Hulun Buir sheep. SNP1: c.144G>A (rs600896367); the arrow indicates the G–A mutation site. SNP2: c.150T>C (rs159876393); the arrow indicates the T–C mutation site. SNP3: c.495G>A (rs400398060); the arrow denotes to the G–A mutation site.

Figure 2

The sequencing peak maps for the ten detected SNP loci of the IGF1R gene in Hulun Buir sheep. SNP4: c.244C>T; the arrow denotes to the C–T mutation site. SNP5: c.714G>A (rs162159917); the arrow demonstrates the G–A mutation site. SNP6: c.924T>C (rs161166969); the arrow indicates the T–C mutation site, reverse sequenced as an A–G change. SNP7: c.939C>T (rs162159919); the arrow pinpoints the C–T mutation site, reverse sequenced as a G–A change. SNP8: c.1305T>C; the arrow points to the T–C mutation site. SNP9: c.1320G>A (rs601806812); the arrow indicates the G–A mutation site. SNP10: c.1401A>G (rs161166977); the arrow indicates the A–G mutation site. SNP11: c.1722T>C (rs161166984); the arrow demonstrates the T–C mutation site, reverse sequenced as an A–G change. SNP12: c.2253C>T (rs193644211); the arrow indicates the C–T mutation site. SNP13: c.2634C>G (rs161167008); the arrow pinpoints the C–G mutation site.

Figure 3

Associations for the SNPs of IGF1 gene with growth traits in Hulun Buir sheep. (A) The comparison of growth traits in SNP1 genotypes of IGF1 gene; WCG = chest girth at weaning (4-month-old); NBL = body length at 9-months-old. (B) The comparison of growth traits in SNP2 genotypes of IGF1 gene; NCG = chest girth at 9-months-old. (C) The comparison of growth traits in SNP3 genotypes of IGF1 gene; 4–9 ADG = average daily gain from 4 to 9-months-old. Different letters (small letters: p < 0.05) above the column indicate significant differences among the different genotypes.

Figure 4

Associations for the SNPs of IGF1R gene with growth traits in Hulun Buir sheep. (A) Association analysis for different genotypes of SNP6 in the IGF1R gene with growth traits; NBL = body length at 9-months-old. (B) The comparison of body weight traits in SNP8 genotypes of IGF1R gene; BW = birth weight; WW = weaning weight (4-month-old); NBW = body weight at 9-months-old; 0–4 ADG = average daily gain from birth to 4-months-old; 0–9 ADG = average daily gain from birth to 9-months-old. (C) Association analyses for different genotypes of SNP8 in IGF1R with body size traits; WBH = body height at 4-months-old; WBL = body length at 4-months-old; WCG = chest girth at weaning (4-months-old); NBH = body height at 9-months-old; NBL = body length at 9-months-old; NCG = chest girth at 9-months-old. (D) The comparison of body weight traits in SNP13 genotypes of IGF1R gene; NBW = body weight at 9-months-old; 0–9 ADG = average daily gain from birth to 9-months-old. (E) Association analyses for different genotypes of SNP13 in the IGF1R with body size traits; WCG = chest girth at weaning (4-month-old); NBH = body height at 9-months-old; NBL = body length at 9-months-old; NCG = chest girth at 9-months-old. Different letters (small letters: p < 0.05; capital letters: p < 0.01) above the column indicate significant differences among the different genotypes.

Figure 5

Linkage disequilibrium plot (r²) and haplotype blocks for SNPs of the IGF1R gene in Hulun Buir sheep. The values in boxes are pairwise SNP correlations (r²); dark red boxes indicate strong LD (r² > 0.33) and light red boxes without numbers represent very weak LD (r² < 0.001).

Figure 6

Linkage disequilibrium plot (r²) and haplotype blocks for SNPs of the IGF1 gene in Hulun Buir sheep. The values within boxes are pairwise SNP correlations (r²) and light red boxes represent very weak LD (r² < 0.001).

Figure 7

Associations for the haplotype combinations of SNPs in the IGF1R gene with growth traits in Hulun Buir sheep. (A) Association analysis for the haplotype combinations (block 1) of the IGF1R gene with growth traits; NBL = body length at 9–months–old. (B) The comparison of body weight traits for the haplotype combinations (block 2) of IGF1R gene in Hulun Buir sheep; BW = birth weight; WW = weaning weight (4–month–old); NBW = body weight at 9–months–old; 0–4 ADG = average daily gain from birth to 4–months–old; 4–9 ADG = average daily gain from 4 to 9–months–old; 0–9 ADG = average daily gain from birth to 9–months–old. (C) Association analyses for the haplotype combinations (block 2) of IGF1R gene with body size traits in Hulun Buir sheep; WBH = body height at 4 months of age; WBL = body length at 4–months–old; WCG = chest girth at weaning (4–month–old); NBH = body height at 9–months–old; NBL = body length at 9–months–old; NCG = chest girth at 9–months–old. Different letters (small letters: p < 0.05; capital letters: p < 0.01) above the column indicate significant differences among the different haplotype combinations.