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Genome-wide association study identified three major QTL for carcass weight including the PLAG1-CHCHD7 QTN for stature in Japanese Black cattle.

Nishimura S, Watanabe T, Mizoshita K, Tatsuda K, Fujita T, Watanabe N, Sugimoto Y, Takasuga A - BMC Genet. (2012)

Bottom Line: In contrast, the most highly associated SNP on BTA 14 was located 2.3-Mb centromeric from the previously identified CW-1 region.Linkage disequilibrium mapping led to a revision of the CW-1 region within a 0.9-Mb interval around the associated SNP, and targeted resequencing followed by association analysis highlighted the quantitative trait nucleotides for bovine stature in the PLAG1-CHCHD7 intergenic region.The allele substitution effects of CW-1, CW-2, and CW-3 were 28.4, 35.3, and 35.0 kg per allele, respectively.

View Article: PubMed Central - HTML - PubMed

Affiliation: Shirakawa Institute of Animal Genetics, Japan Livestock Technology Association, Odakura, Nishigo, Fukushima, 961-8061, Japan.

ABSTRACT

Background: Significant quantitative trait loci (QTL) for carcass weight were previously mapped on several chromosomes in Japanese Black half-sib families. Two QTL, CW-1 and CW-2, were narrowed down to 1.1-Mb and 591-kb regions, respectively. Recent advances in genomic tools allowed us to perform a genome-wide association study (GWAS) in cattle to detect associations in a general population and estimate their effect size. Here, we performed a GWAS for carcass weight using 1156 Japanese Black steers.

Results: Bonferroni-corrected genome-wide significant associations were detected in three chromosomal regions on bovine chromosomes (BTA) 6, 8, and 14. The associated single nucleotide polymorphisms (SNP) on BTA 6 were in linkage disequilibrium with the SNP encoding NCAPG Ile442Met, which was previously identified as a candidate quantitative trait nucleotide for CW-2. In contrast, the most highly associated SNP on BTA 14 was located 2.3-Mb centromeric from the previously identified CW-1 region. Linkage disequilibrium mapping led to a revision of the CW-1 region within a 0.9-Mb interval around the associated SNP, and targeted resequencing followed by association analysis highlighted the quantitative trait nucleotides for bovine stature in the PLAG1-CHCHD7 intergenic region. The association on BTA 8 was accounted for by two SNP on the BovineSNP50 BeadChip and corresponded to CW-3, which was simultaneously detected by linkage analyses using half-sib families. The allele substitution effects of CW-1, CW-2, and CW-3 were 28.4, 35.3, and 35.0 kg per allele, respectively.

Conclusion: The GWAS revealed the genetic architecture underlying carcass weight variation in Japanese Black cattle in which three major QTL accounted for approximately one-third of the genetic variance.

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Conditioned analyses. To examine whether the associations detected on a chromosome were independent, a conditioned analysis was performed by including a genotype of the most significant SNP on the chromosome as a covariate in the model. Red and blue dots represent p values in –log10 scale before and after conditioning, respectively. Large squares indicate the most significant SNP in the respective chromosomes. (A) BTA 14. (B) BTA 6. (C1) BTA 8. In BTA 8, Hapmap40466-BTA-82123 reached nearly genome-wide significance with conditioning on BTA-52694-no-rs (C1), while the association of BTA-52694-no-r became stronger with conditioning on Hapmap40466-BTA-8212 (C2, green dots). When conditioned on both SNP, associations of the surrounding SNP disappeared (C3, orange dots).
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Figure 2: Conditioned analyses. To examine whether the associations detected on a chromosome were independent, a conditioned analysis was performed by including a genotype of the most significant SNP on the chromosome as a covariate in the model. Red and blue dots represent p values in –log10 scale before and after conditioning, respectively. Large squares indicate the most significant SNP in the respective chromosomes. (A) BTA 14. (B) BTA 6. (C1) BTA 8. In BTA 8, Hapmap40466-BTA-82123 reached nearly genome-wide significance with conditioning on BTA-52694-no-rs (C1), while the association of BTA-52694-no-r became stronger with conditioning on Hapmap40466-BTA-8212 (C2, green dots). When conditioned on both SNP, associations of the surrounding SNP disappeared (C3, orange dots).

Mentions: The strongest association was detected with Hapmap46986-BTA-34282 (p = 1.03 × 10-12) located at 23.5 Mb on BTA 14 (Btau4.0; Figure 2A; Table 1). This and three other significant SNP located from 23.5 to 26.2 Mb on BTA 14 were in moderate linkage disequilibrium (LD) with linkage disequilibrium coefficients (r2) ranging from 0.23 to 0.79. The second strongest association was obtained with Hapmap26308-BTC-057761 (p = 9.65 × 10-12) on BTA 6, which had 11 other significant SNP in the interval (Figure 2B; Table 1). Eleven SNP, including Hapmap26308-BTC-057761, located within 3.5 Mb from 35.7 to 39.2 Mb and were in strong LD with r2 ranging from 0.65 to 1.00. A residual SNP was 7.9 Mb from them, but in strong LD with the 11 SNP (r2 = 0.62-0.73). An extended LD of this region was also observed in a previous study [3], which is probably due to a specific (local) lineage of the Q allele. On BTA 8, 3 SNP locating from 88.7 Mb to 89.4 Mb reached genome-wide significance (Figure 2C). The most significant SNP was BTA-52694-no-rs (p = 4.24 x 10-9; Table 1). In this case, the LD among the 3 SNP was relatively weak with r2 ranging from 0.14 to 0.35.


Genome-wide association study identified three major QTL for carcass weight including the PLAG1-CHCHD7 QTN for stature in Japanese Black cattle.

Nishimura S, Watanabe T, Mizoshita K, Tatsuda K, Fujita T, Watanabe N, Sugimoto Y, Takasuga A - BMC Genet. (2012)

Conditioned analyses. To examine whether the associations detected on a chromosome were independent, a conditioned analysis was performed by including a genotype of the most significant SNP on the chromosome as a covariate in the model. Red and blue dots represent p values in –log10 scale before and after conditioning, respectively. Large squares indicate the most significant SNP in the respective chromosomes. (A) BTA 14. (B) BTA 6. (C1) BTA 8. In BTA 8, Hapmap40466-BTA-82123 reached nearly genome-wide significance with conditioning on BTA-52694-no-rs (C1), while the association of BTA-52694-no-r became stronger with conditioning on Hapmap40466-BTA-8212 (C2, green dots). When conditioned on both SNP, associations of the surrounding SNP disappeared (C3, orange dots).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3403917&req=5

Figure 2: Conditioned analyses. To examine whether the associations detected on a chromosome were independent, a conditioned analysis was performed by including a genotype of the most significant SNP on the chromosome as a covariate in the model. Red and blue dots represent p values in –log10 scale before and after conditioning, respectively. Large squares indicate the most significant SNP in the respective chromosomes. (A) BTA 14. (B) BTA 6. (C1) BTA 8. In BTA 8, Hapmap40466-BTA-82123 reached nearly genome-wide significance with conditioning on BTA-52694-no-rs (C1), while the association of BTA-52694-no-r became stronger with conditioning on Hapmap40466-BTA-8212 (C2, green dots). When conditioned on both SNP, associations of the surrounding SNP disappeared (C3, orange dots).
Mentions: The strongest association was detected with Hapmap46986-BTA-34282 (p = 1.03 × 10-12) located at 23.5 Mb on BTA 14 (Btau4.0; Figure 2A; Table 1). This and three other significant SNP located from 23.5 to 26.2 Mb on BTA 14 were in moderate linkage disequilibrium (LD) with linkage disequilibrium coefficients (r2) ranging from 0.23 to 0.79. The second strongest association was obtained with Hapmap26308-BTC-057761 (p = 9.65 × 10-12) on BTA 6, which had 11 other significant SNP in the interval (Figure 2B; Table 1). Eleven SNP, including Hapmap26308-BTC-057761, located within 3.5 Mb from 35.7 to 39.2 Mb and were in strong LD with r2 ranging from 0.65 to 1.00. A residual SNP was 7.9 Mb from them, but in strong LD with the 11 SNP (r2 = 0.62-0.73). An extended LD of this region was also observed in a previous study [3], which is probably due to a specific (local) lineage of the Q allele. On BTA 8, 3 SNP locating from 88.7 Mb to 89.4 Mb reached genome-wide significance (Figure 2C). The most significant SNP was BTA-52694-no-rs (p = 4.24 x 10-9; Table 1). In this case, the LD among the 3 SNP was relatively weak with r2 ranging from 0.14 to 0.35.

Bottom Line: In contrast, the most highly associated SNP on BTA 14 was located 2.3-Mb centromeric from the previously identified CW-1 region.Linkage disequilibrium mapping led to a revision of the CW-1 region within a 0.9-Mb interval around the associated SNP, and targeted resequencing followed by association analysis highlighted the quantitative trait nucleotides for bovine stature in the PLAG1-CHCHD7 intergenic region.The allele substitution effects of CW-1, CW-2, and CW-3 were 28.4, 35.3, and 35.0 kg per allele, respectively.

View Article: PubMed Central - HTML - PubMed

Affiliation: Shirakawa Institute of Animal Genetics, Japan Livestock Technology Association, Odakura, Nishigo, Fukushima, 961-8061, Japan.

ABSTRACT

Background: Significant quantitative trait loci (QTL) for carcass weight were previously mapped on several chromosomes in Japanese Black half-sib families. Two QTL, CW-1 and CW-2, were narrowed down to 1.1-Mb and 591-kb regions, respectively. Recent advances in genomic tools allowed us to perform a genome-wide association study (GWAS) in cattle to detect associations in a general population and estimate their effect size. Here, we performed a GWAS for carcass weight using 1156 Japanese Black steers.

Results: Bonferroni-corrected genome-wide significant associations were detected in three chromosomal regions on bovine chromosomes (BTA) 6, 8, and 14. The associated single nucleotide polymorphisms (SNP) on BTA 6 were in linkage disequilibrium with the SNP encoding NCAPG Ile442Met, which was previously identified as a candidate quantitative trait nucleotide for CW-2. In contrast, the most highly associated SNP on BTA 14 was located 2.3-Mb centromeric from the previously identified CW-1 region. Linkage disequilibrium mapping led to a revision of the CW-1 region within a 0.9-Mb interval around the associated SNP, and targeted resequencing followed by association analysis highlighted the quantitative trait nucleotides for bovine stature in the PLAG1-CHCHD7 intergenic region. The association on BTA 8 was accounted for by two SNP on the BovineSNP50 BeadChip and corresponded to CW-3, which was simultaneously detected by linkage analyses using half-sib families. The allele substitution effects of CW-1, CW-2, and CW-3 were 28.4, 35.3, and 35.0 kg per allele, respectively.

Conclusion: The GWAS revealed the genetic architecture underlying carcass weight variation in Japanese Black cattle in which three major QTL accounted for approximately one-third of the genetic variance.

Show MeSH