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* Department of Ruminants and Genetics, Agricultural Research Organization, P.O.B. 6, Bet-Dagan 50-250, Israel
Department of Animal Breeding and Genetics, Justus-Liebig-University Giessen, Ludwigstrasse 21b, 35390 Giessen, Germany
1 Corresponding author: Georg.Erhardt{at}agrar.uni-giessen.de
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Key Words: ATP binding cassette G2 gene • Bos taurus chromosome 6 • single nucleotide polymorphism
Many studies have found segregating QTL for milk production traits on Bos taurus chromosome (BTA) 6 in different dairy cattle populations (reviewed by Khatkar et al., 2004; http://bovineqtl.tamu.edu/index.html). Cohen-Zinder et al. (2005) found a single nucleotide polymorphism (A/C) in exon 14 capable of encoding a substitution of tyrosine-581 to serine (Y581S) in the ABCG2 transporter gene. They provided evidence that Y581S is the causative polymorphism for the QTL on BTA6 affecting milk yield and composition. The protein encoded by ABCG2, a member of the ATP binding cassette (ABC) superfamily, transports various xenobiotics and cytostatic drugs across the plasma membrane (Litman et al., 2000). The ABCG2 gene was not expressed in virgin mice, but was greatly induced during late pregnancy and especially during lactation (Jonker et al., 2005). The effects of the ABCG2A allele, which decreases milk yield and increases protein and fat concentration, are economically favorable for most selection indexes used in dairy cattle breeding programs (Miglior et al., 2005). Thus, as proposed by several studies reviewed by Weller (2001), rates of genetic gain can be increased by direct selection on this allele. However, if the favorable allele is already at high frequency, then the possible gain by direct selection is limited (Cohen-Zinder et al., 2005).
The first identified causative gene for a QTL in dairy cattle, DGAT1, is located on BTA14 and chiefly affects milk fat percentage (Grisart et al., 2002). Kaupe et al. (2004) estimated allele frequencies for DGAT1 in 38 cattle breeds from 5 continents, and found that frequencies of the 2 alleles ranged from zero to fixation. The aim of this study was to determine the allele frequencies for ABCG2 using the same DNA resource, with the addition of the Israeli and US Holstein breeds, to predict the genetic gain obtainable by fixation of the favorable allele.
The analysis included 341 Israeli and 9 US Holstein bulls genotyped previously (Cohen-Zinder et al., 2005), and 724 individuals from 33 additional Bos taurus and Bos indicus breeds (Kaupe et al., 2004) that were genotyped for this single nucleotide polymorphism by DNA MassArray technology (Sequenom Inc., San Diego, CA) following Cohen-Zinder et al. (2005). Nine DNA samples determined to be heterozygous by MassArray were sequenced. All traces showed double peaks (A/C), validating the MassArray genotypes. Allele frequencies and the corresponding standard errors (SE) were calculated using SPSS V 12.0 (SPSS, Inc., Chicago, IL).
Allele frequencies for the ABCG2 gene in the 35 breeds are presented in Table 1
. The ABCG2A allele was predominant in all populations. The ABCG2C allele was not detected in any of the 3 Bos indicus breeds analyzed, but was detected in 12 Bos taurus breeds: Belgian Blue (beef), Belgian Blue Mix, British Friesian, Bohemian Red, East Anatolian Red, German Angus, German Black Pied, German Brown, German Simmental, Israeli Holstein, Menorquina, and US Holstein. In these breeds, allele frequencies of ABCG2A ranged from 80% in Israeli Holstein to 99% in Bohemian Red. Observed heterozygote frequencies were very close to the expected values, by Hardy-Weinberg equilibrium, for all breeds in which both alleles were segregating. The ABCG2C allele was detected in most of the cattle breeds that segregated for the QTL; including the US, German, and Israeli dairy breeds (Khatkar et al., 2004). In view of the high frequency of the ABCG2A allele across all breeds, the genetic gain expected from selection for this allele may be limited. From 1990 through 2002 frequency of the ABCG2A allele in the Israeli Holstein population increased from 0.62 to 0.77; and mean breeding values in the cow population increased by 327 kg of milk, 34.2 kg of fat, 30.2 kg of protein, 0.21% fat, and 0.19% protein. These changes correspond to the adoption of a breeding index in 1991 based chiefly on protein with a negative weight for milk yield. Assuming additive gene action and that the allelic substitution effect is 0.2% protein (Cohen-Zinder et al., 2005), the gain obtained by raising the frequency of the ABCG2A allele by 0.1 should be 0.04% protein. Thus, the increase of 0.15 in the frequency of the ABCG2A allele should have resulted in a gain of 0.06% protein, which accounts for only one-third of the realized gain in protein concentration obtained during these 12 yr. The remainder of this gain must be due to other genes.
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Received for publication March 21, 2006. Accepted for publication July 5, 2006.
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  J. I. Weller, M. Golik, S. Reikhav, R. Domochovsky, E. Seroussi, and M. Ron Detection and Analysis of Quantitative Trait Loci Affecting Production and Secondary Traits on Chromosome 7 in Israeli Holsteins J Dairy Sci, February 1, 2008; 91(2): 802 - 813. [Abstract] [Full Text] [PDF]
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