Genetic support for a quantitative trait nucleotide in the ABCG2 gene affecting milk composition of dairy cattle

BACKGROUND: Our group has previously identified a quantitative trait locus (QTL) affecting fat and protein percentages on bovine chromosome 6, and refined the QTL position to a 420-kb interval containing six genes. Studies performed in other cattle populations have proposed polymorphisms in two different genes (ABCG2 and OPN) as the underlying functional QTL nucleotide. Due to these conflicting results, we have included these QTNs, together with a large collection of new SNPs produced from PCR sequencing, in a dense marker map spanning the QTL region, and reanalyzed the data using a combined linkage and linkage disequilibrium approach. RESULTS: Our results clearly exclude the OPN SNP (OPN_3907) as causal site for the QTL. Among 91 SNPs included in the study, the ABCG2 SNP (ABCG2_49) is clearly the best QTN candidate. The analyses revealed the presence of only one QTL for the percentage traits in the tested region. This QTL was completely removed by correcting the analysis for ABCG2_49. Concordance between the sires' marker genotypes and segregation status for the QTL was found for ABCG2_49 only. The C allele of ABCG2_49 is found in a marker haplotype that has an extremely negative effect on fat and protein percentages and positive effect on milk yield. Of the 91 SNPs, ABCG2_49 was the only marker in perfect linkage disequilibrium with the QTL. CONCLUSION: Based on our results, OPN_3907 can be excluded as the polymorphism underlying the QTL. The results of this and other papers strongly suggest the [A/C] mutation in ABCG2_49 as the causal mutation, although the possibility that ABCG2_49 is only a marker in perfect LD with the true mutation can not be completely ruled out.