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Letter

Identification of a missense mutation in the bovine ABCG2 gene with a major effect on the QTL on chromosome 6 affecting milk yield and composition in Holstein cattle

¹ Institute of Animal Sciences, Agricultural Research Organization, Bet-Dagan 50250, Israel ² Department of Animal Sciences, University of Illinois, Urbana, Illinois 61801, USA ³ W.M. Keck Center for Comparative and Functional Genomics, University of Illinois, Urbana, Illinois 61801, USA

We previously localized a quantitative trait locus (QTL) on chromosome 6 affecting milk fat and protein concentration to a 4-cM confidence interval, centered on the microsatellite BM143. We characterized the genes and sequence variation in this region and identified common haplotypes spanning five polymorphic sites in the genes IBSP, SPP1, PKD2, and ABCG2 for two sires heterozygous for this QTL. Expression of SPP1 and ABCG2 in the bovine mammary gland increased from parturition through lactation. SPP1 and all the coding exons of ABCG2 and PKD2 were sequenced for these two sires. The single nucleotide change capable of encoding a substitution of tyrosine-581 to serine (Y581S) in the ABCG2 transporter was the only polymorphism corresponding to the segregation status of all 3 heterozygous and 15 homozygous sires for the QTL in the Israeli and U.S. Holstein populations. The allele substitution fixed effects on the genetic evaluations of 335 Israeli sires were –341 kg milk, +0.16% fat, and +0.13% protein (F-value = 200). No other polymorphism gave significant effect for fat and protein concentration in models that also included Y581S. The allele substitution effects on the genetic evaluations of 670 cows, daughters of two heterozygous sires, were –226 kg milk, 0.09% fat, and 0.08% protein (F-value = 394), with partial dominance towards the 581S homozygotes. We therefore propose that Y581S in ABCG2 is the causative site for this QTL.

⁴ These authors contributed equally to this work.

⁵ Corresponding author.
E-mail weller{at}agri.huji.ac.il; fax 973-8-9470587.

[Supplemental material is available online at www.genome.org. The sequence data from this study have been submitted to EMBL/GenBank/DDBJ under accession nos. AJ871966, AJ871964, AJ871963, AJ871176, AJ871967, AJ871968, AJ871965, AJ877268.]

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