Eleven Israeli Holstein families including 5221 cows were analyzed by a daughter design for eight economic traits: milk, fat and protein production, fat and protein percentage, somatic cell score (SCS), herd-life, and female fertility. The cows were genotyped for 73 microsatellites with maximum spacing between markers of 53 cM. There were 86,304 informative genotypes. Preliminary analysis was by ANOVA of each trait, with the marker effect nested within sire. Significance was determined by controlling the false discovery rate at 0.4, after excluding markers with genome-wide significance for at least a single trait, and traits without any significant effects at this level. Thus, four markers on chromosomes 6 and 14 and female fertility were excluded. There remained 40 significant marker-trait combinations, and it is expected that 24 of these are true effects. To perform interval mapping for the families with significant contrasts, 21 additional markers were genotyped on chromosomes 2, 7, and 27. The bootstrap confidence intervals for gene effect did not include zero for protein percent on chromosome 2 and fat yield, protein yield, and SCS on chromosome 7. Quantitative trait locus heterozygosity was 33%, which is consistent with the hypothesis that only two alleles are segregating with unequal allele frequency.
A method is described on the basis of a modification of the granddaughter design to obtain estimates of quantitative trait loci (QTL) allele frequencies in dairy cattle populations and to determine QTL genotypes for both homozygous and heterozygous grandsires. The method is based on determining the QTL allele passed from grandsires to their maternal granddaughters using haplotypes consisting of several closely linked genetic markers. This method was applied to simulated data of 10 grandsire families, each with 500 granddaughters, and a QTL with a substitution effect of 0.4 phenotypic standard deviations and to actual data for a previously analyzed QTL in the center of chromosome 6, with substitution effect of 1 phenotypic standard deviation on protein percentage. In the simulated data the standard error for the estimated QTL substitution effect with four closely linked multiallelic markers was only 7% greater than the expected standard error with completely correct identification of QTL allele origin. The method estimated the population QTL allelic frequency as 0.64 +/- 0.07, compared to the simulated value of 0.7. In the actual data, the frequency of the allele that increases protein percentage was estimated as 0.63 +/- 0.06. In both data sets the hypothesis of equal allelic frequencies was rejected at P < 0.05.
Nine Israeli Holstein sire families with 2978 daughters were analyzed for quantitative trait loci effects on chromosome 6 for five milk production traits by a daughter design. All animals were genotyped for 2 markers. The three families with significant effects were genotyped for up to 10 additional markers spanning positions 0-122 cM of BTA6. Two sires were segregating for a locus affecting protein and fat percentage near position 55 cM with an estimated substitution effect of 0.18% protein, which is equivalent to one phenotypic standard deviation. This locus was localized to a confidence interval of 4 cM. One of these sires was also heterozygous for a locus affecting milk, fat, and protein production near the centromere. The hypothesis of two segregating loci was verified by multiple regression analysis. A third sire was heterozygous for a locus affecting milk and protein percentage near the telomeric end of the chromosome. Possible candidates for the major quantitative gene near position 55 cM were determined by comparative mapping. IBSP and SSP1 were used as anchors for the orthologous region on human chromosome 4. Twelve genes were detected within a 2-Mbp sequence. None of these genes have been previously associated with lactogenesis.