Fine mapping and physical characterization of two linked quantitative trait loci affecting milk fat yield in dairy cattle on BTA26

Abstract

Previously, a highly significant QTL affecting fat yield and protein yield and mapped to the bovine BTA26 chromosome has been reported to segregate in the French Holstein cattle population. To confirm and refine the location of this QTL, the original detection experiment was extended by adding 12 new families and genotyping 25 additional microsatellite markers (including 11 newly developed markers). Data were then analyzed by an approach combining both linkage and linkage disequilibrium information, making it possible to identify two linked QTL separated by 20 cM corresponding to approximately 29 Mb. The presence of a QTL affecting protein yield was confirmed but its position was found to be more telomeric than the two QTLunderlying fat yield. Each identified QTL affecting milk fat yield was physically mapped within a segment estimated to be <500 kb. Two strong functional candidate genes involved, respectively, in fatty acid metabolism and membrane permeability were found to be localized within this segment while other functional candidate genes were discarded. A haplotype comprising the favorable allele at each QTL position appears to be overrepresented in the artificial insemination bull population.

Figure 1.

(A) The BTA26 linkage map constructed in this study. (B) The map is anchored to the BTA26 physical map and (C) to the HSA10 genome sequence assembly. (D) The previous BTA26 RH map is also given. See text for details.

Figure 2.

Linkage analysis results from regression LA. The number of bootstrap samples and the informativity have been rescaled.

Figure 3.

LDLA results and comparison with results from variance component linkage analysis alone. The two-QTL LDLA model 1 (respectively, 2) LRT curve plots the test of the LDLA model fitting the two-QTL bracket effect against the model fitting one QTL at the [BMS907/INRA311] (respectively, [BES26_1/HAUT27]) marker bracket.

Figure 4.

Two-QTL LDLA results for milk fat yield. LRT values (two-QTL segregating against no-QTL segregating) are plotted in two dimensions corresponding to each possible pair of marker bracket effects.

Figure 5.

Haplotype effect distributions for the two most likely marker brackets.

Figure 6.

Haplotypes segregating among the 21 sires of the granddaughter design. The father (or grandfather, when followed by an asterisk) is also mentioned when it is included as a sire in the granddaughter design. The N-value (see materials and methods) is given for the two most likely QTL marker bracket positions. Numbers in boldface and boldface italic type correspond to sires heterozygous at the corresponding position according to the N-statistic at a 5 and 10% significant threshold, respectively. Similarly the t-tests from regression LA are reported for the two peak positions (see text). Finally, the two haplotypes spanning the 30-cM interval containing the two QTL are included. Positions of the markers are indicated with brackets. The common haplotype supposed to carry the two favorable alleles for the two QTL is shown in boldface type.