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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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Recombinants for a 5 Mb region that includes CORIN, PDGFRA, KIT, and KDR. The animal identifier for each genotype (AA, AN, NA, NN where allele from sire is listed first) is followed in brackets by the raw degree of black score and the residual after adjusting for fixed effects of sex, family, and season; vertical solid black lines indicate the interval most likely to contain the reddening locus under the assumption that reddening is associated with the Nellore allele and acts as a recessive; genes within this region (excluding model genes designated as “LOC”) are plotted based on their start and end base pair positions using “/”.
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Figure 3: Recombinants for a 5 Mb region that includes CORIN, PDGFRA, KIT, and KDR. The animal identifier for each genotype (AA, AN, NA, NN where allele from sire is listed first) is followed in brackets by the raw degree of black score and the residual after adjusting for fixed effects of sex, family, and season; vertical solid black lines indicate the interval most likely to contain the reddening locus under the assumption that reddening is associated with the Nellore allele and acts as a recessive; genes within this region (excluding model genes designated as “LOC”) are plotted based on their start and end base pair positions using “/”.

Mentions: Because long-range haplotypes are recovered in this population due to linkage, we considered candidate genes up to 5 Mb from the leading SNP. The gene corin serine peptidase (CORIN) is located 3.7 Mb upstream of PDGFRA and is associated with lighter coat colors in mice [21]. Haplotypes and breed-of-origin were assigned as before and 13 recombinants with degree of black scores were identified (Figure 3). Assuming that the reddening associated with the Nellore allele was recessive, the interval could be refined to a region between 71708424 and 72478577 bp on BTA6 (Figure 3), thereby eliminating the coding sequences of KIT, KDR and CORIN as candidates. Although we cannot rule out possible effects of long-range regulatory elements associated with these genes, based on its location within the refined interval, PDGFRA appears to be the strongest positional candidate for the reddening phenotype.


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)

Recombinants for a 5 Mb region that includes CORIN, PDGFRA, KIT, and KDR. The animal identifier for each genotype (AA, AN, NA, NN where allele from sire is listed first) is followed in brackets by the raw degree of black score and the residual after adjusting for fixed effects of sex, family, and season; vertical solid black lines indicate the interval most likely to contain the reddening locus under the assumption that reddening is associated with the Nellore allele and acts as a recessive; genes within this region (excluding model genes designated as “LOC”) are plotted based on their start and end base pair positions using “/”.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Recombinants for a 5 Mb region that includes CORIN, PDGFRA, KIT, and KDR. The animal identifier for each genotype (AA, AN, NA, NN where allele from sire is listed first) is followed in brackets by the raw degree of black score and the residual after adjusting for fixed effects of sex, family, and season; vertical solid black lines indicate the interval most likely to contain the reddening locus under the assumption that reddening is associated with the Nellore allele and acts as a recessive; genes within this region (excluding model genes designated as “LOC”) are plotted based on their start and end base pair positions using “/”.
Mentions: Because long-range haplotypes are recovered in this population due to linkage, we considered candidate genes up to 5 Mb from the leading SNP. The gene corin serine peptidase (CORIN) is located 3.7 Mb upstream of PDGFRA and is associated with lighter coat colors in mice [21]. Haplotypes and breed-of-origin were assigned as before and 13 recombinants with degree of black scores were identified (Figure 3). Assuming that the reddening associated with the Nellore allele was recessive, the interval could be refined to a region between 71708424 and 72478577 bp on BTA6 (Figure 3), thereby eliminating the coding sequences of KIT, KDR and CORIN as candidates. Although we cannot rule out possible effects of long-range regulatory elements associated with these genes, based on its location within the refined interval, PDGFRA appears to be the strongest positional candidate for the reddening phenotype.

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