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Identification of a major locus interacting with MC1R and modifying black coat color in an F₂ Nellore-Angus population.

Hanna LL, Sanders JO, Riley DG, Abbey CA, Gill CA - Genet. Sel. Evol. (2014)

Bottom Line: In most mammals, these alleles are presumed to follow the dominance model of E(D) > E+ > e, although exceptions are found.Fitting SNP haplotypes for a 1 Mb interval that contained all three genes and centered on KIT accounted for the majority of the variation attributed to this major locus, which suggests that one of these genes or associated regulatory elements, is responsible for the majority of variation in degree of reddening.A higher density marker panel and functional analyses will be required to validate the role of PDGFRA or other regulatory variants and their interaction with MC1R for the modification of black coat color in Bos indicus influenced cattle.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Animal Science, Texas A& M University, College Station, TX 77843, USA. clare-gill@tamu.edu.

ABSTRACT

Background: In cattle, base color is assumed to depend on the enzymatic activity specified by the MC1R locus, i.e. the extension locus, with alleles coding for black (E(D)), red (e), and wild-type (E+). In most mammals, these alleles are presumed to follow the dominance model of E(D) > E+ > e, although exceptions are found. In Bos indicus x Bos taurus F2 cattle, some E(D)E+ heterozygotes are discordant with the dominance series for MC1R and display various degrees of red pigmentation on an otherwise predicted black background. The objective of this study was to identify loci that modify black coat color in these individuals.

Results: Reddening was classified with a subjective scoring system. Interval analyses identified chromosome-wide suggestive (P < 0.05) and significant (P < 0.01) QTL on bovine chromosomes (BTA) 4 and 5, although these were not confirmed using single-marker association or Bayesian methods. Evidence of a major locus (F = 114.61) that affects reddening was detected between 60 and 73 Mb on BTA 6 (Btau4.0 build), and at 72 Mb by single-marker association and Bayesian methods. The posterior mean of the genetic variance for this region accounted for 43.75% of the genetic variation in reddening. This region coincided with a cluster of tyrosine kinase receptor genes (PDGFRA, KIT and KDR). Fitting SNP haplotypes for a 1 Mb interval that contained all three genes and centered on KIT accounted for the majority of the variation attributed to this major locus, which suggests that one of these genes or associated regulatory elements, is responsible for the majority of variation in degree of reddening.

Conclusions: Recombinants in a 5 Mb region surrounding the cluster of tyrosine kinase receptor genes implicated PDGFRA as the strongest positional candidate gene. A higher density marker panel and functional analyses will be required to validate the role of PDGFRA or other regulatory variants and their interaction with MC1R for the modification of black coat color in Bos indicus influenced cattle.

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Combined plots of QTL analyses using Btau4.0 build with interval and Bayesian methods. (A) Original model with chromosome-wide significant thresholds (P = 0.01 and 0.05) as the dashed and dotted lines, respectively, for the interval analysis, while the posterior probability of association (PPAw) is plotted for the Bayesian analysis; (B) original model using single-marker association methods with absolute value of t-statistics and P = 0.05 threshold as the dashed line; (C) model including KIT region breed-of-origin genotypes with chromosome-wide significant thresholds as described before.
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Figure 2: Combined plots of QTL analyses using Btau4.0 build with interval and Bayesian methods. (A) Original model with chromosome-wide significant thresholds (P = 0.01 and 0.05) as the dashed and dotted lines, respectively, for the interval analysis, while the posterior probability of association (PPAw) is plotted for the Bayesian analysis; (B) original model using single-marker association methods with absolute value of t-statistics and P = 0.05 threshold as the dashed line; (C) model including KIT region breed-of-origin genotypes with chromosome-wide significant thresholds as described before.

Mentions: Unexpectedly, a major locus associated with degree of black was detected on BTA6 (Bos taurus chromosome 6) at an average location of 71 Mb (95% CI from 60 to 73 Mb) by interval analysis (Table 1). Suggestive (P < 0.05) and significant (P < 0.01) QTL were also identified on BTA4 and 5, respectively. When 10 of the 29 bovine chromosomes generated runtime errors due to long strings of heterozygous SNPs, single-marker association analysis was run and detected the major locus on BTA6 (Bonferroni corrected P = 3.88e-23), but did not confirm the QTL on BTA4 or 5. Bayesian association analysis also confirmed the major locus on BTA6 (but not those on BTA4 or 5) with PPAw = 1.00 (Figure 2A-B). The posterior mean of genetic variance for the 72 Mb region accounted for 43.75% of the total genetic variance using Bayesian association analysis, and an expanded region from 68 Mb to 72 Mb region accounted for 44.19% of the total genetic variance. Posterior means of variances and genomic heritability are in Table 2.


Identification of a major locus interacting with MC1R and modifying black coat color in an F₂ Nellore-Angus population.

Hanna LL, Sanders JO, Riley DG, Abbey CA, Gill CA - Genet. Sel. Evol. (2014)

Combined plots of QTL analyses using Btau4.0 build with interval and Bayesian methods. (A) Original model with chromosome-wide significant thresholds (P = 0.01 and 0.05) as the dashed and dotted lines, respectively, for the interval analysis, while the posterior probability of association (PPAw) is plotted for the Bayesian analysis; (B) original model using single-marker association methods with absolute value of t-statistics and P = 0.05 threshold as the dashed line; (C) model including KIT region breed-of-origin genotypes with chromosome-wide significant thresholds as described before.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3924621&req=5

Figure 2: Combined plots of QTL analyses using Btau4.0 build with interval and Bayesian methods. (A) Original model with chromosome-wide significant thresholds (P = 0.01 and 0.05) as the dashed and dotted lines, respectively, for the interval analysis, while the posterior probability of association (PPAw) is plotted for the Bayesian analysis; (B) original model using single-marker association methods with absolute value of t-statistics and P = 0.05 threshold as the dashed line; (C) model including KIT region breed-of-origin genotypes with chromosome-wide significant thresholds as described before.
Mentions: Unexpectedly, a major locus associated with degree of black was detected on BTA6 (Bos taurus chromosome 6) at an average location of 71 Mb (95% CI from 60 to 73 Mb) by interval analysis (Table 1). Suggestive (P < 0.05) and significant (P < 0.01) QTL were also identified on BTA4 and 5, respectively. When 10 of the 29 bovine chromosomes generated runtime errors due to long strings of heterozygous SNPs, single-marker association analysis was run and detected the major locus on BTA6 (Bonferroni corrected P = 3.88e-23), but did not confirm the QTL on BTA4 or 5. Bayesian association analysis also confirmed the major locus on BTA6 (but not those on BTA4 or 5) with PPAw = 1.00 (Figure 2A-B). The posterior mean of genetic variance for the 72 Mb region accounted for 43.75% of the total genetic variance using Bayesian association analysis, and an expanded region from 68 Mb to 72 Mb region accounted for 44.19% of the total genetic variance. Posterior means of variances and genomic heritability are in Table 2.

Bottom Line: In most mammals, these alleles are presumed to follow the dominance model of E(D) > E+ > e, although exceptions are found.Fitting SNP haplotypes for a 1 Mb interval that contained all three genes and centered on KIT accounted for the majority of the variation attributed to this major locus, which suggests that one of these genes or associated regulatory elements, is responsible for the majority of variation in degree of reddening.A higher density marker panel and functional analyses will be required to validate the role of PDGFRA or other regulatory variants and their interaction with MC1R for the modification of black coat color in Bos indicus influenced cattle.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Animal Science, Texas A& M University, College Station, TX 77843, USA. clare-gill@tamu.edu.

ABSTRACT

Background: In cattle, base color is assumed to depend on the enzymatic activity specified by the MC1R locus, i.e. the extension locus, with alleles coding for black (E(D)), red (e), and wild-type (E+). In most mammals, these alleles are presumed to follow the dominance model of E(D) > E+ > e, although exceptions are found. In Bos indicus x Bos taurus F2 cattle, some E(D)E+ heterozygotes are discordant with the dominance series for MC1R and display various degrees of red pigmentation on an otherwise predicted black background. The objective of this study was to identify loci that modify black coat color in these individuals.

Results: Reddening was classified with a subjective scoring system. Interval analyses identified chromosome-wide suggestive (P < 0.05) and significant (P < 0.01) QTL on bovine chromosomes (BTA) 4 and 5, although these were not confirmed using single-marker association or Bayesian methods. Evidence of a major locus (F = 114.61) that affects reddening was detected between 60 and 73 Mb on BTA 6 (Btau4.0 build), and at 72 Mb by single-marker association and Bayesian methods. The posterior mean of the genetic variance for this region accounted for 43.75% of the genetic variation in reddening. This region coincided with a cluster of tyrosine kinase receptor genes (PDGFRA, KIT and KDR). Fitting SNP haplotypes for a 1 Mb interval that contained all three genes and centered on KIT accounted for the majority of the variation attributed to this major locus, which suggests that one of these genes or associated regulatory elements, is responsible for the majority of variation in degree of reddening.

Conclusions: Recombinants in a 5 Mb region surrounding the cluster of tyrosine kinase receptor genes implicated PDGFRA as the strongest positional candidate gene. A higher density marker panel and functional analyses will be required to validate the role of PDGFRA or other regulatory variants and their interaction with MC1R for the modification of black coat color in Bos indicus influenced cattle.

Show MeSH
Related in: MedlinePlus