A positional candidate gene approach to the discovery of quantitative trait loci on bovine chromosome 5

Twenty-four microsatellite markers were screened across 701 members of the three generation Angus x Brahman "Angleton" pedigree. A genetic map based on meiotic exchange was constructed from the microsatellite data for Bos taurus chromosome 5 (BTA5). Phenotypic data for 64 growth and carcass merit traits were collected for 543 progeny produced and slaughtered for the project. Composite interval analyses of the genotypic and phenotypic data were performed to search for quantitative trait loci (QTL) on BTA5. QTL were detected (LOD > 3) in three regions of the chromosome. A QTL in the centromeric region appeared to affect quality grade and marbling. A QTL in the interstitial region of the chromosome affected birth weight, weaning weight, out-of-Angleton weight, ribeye area, kidney, pelvic and heart fat and dressing percent. A QTL in the telomeric region appeared to affect weaning weight and Warner Bratzler shear force.;PCR primers for all publicly available markers in the three critical intervals were used to screen a bovine bacterial artificial chromosome (BAC) library. Positive BAC clones were mapped to BTA5 by fluorescence in situ hybridization (FISH) and sequence analysis of the PCR products from each clone. Approximately 20 shotgun subclones of each validated BAC were sequenced and evaluated by BLAST similarity searches for homologs in the human sequence databases to define intervals in the human genome map to be screened for candidate genes that might be responsible for the QTL effects on BTA5.;The three BACs identified and subcloned in the centromeric region of BTA5 contained sequences of long and short interspersed repetitive sequences (LINEs and SINEs) but not homologs to human sequences. Results from the homology study in the interstitial region produced multiple ties to the human RH map and demonstrated that multiple chromosomal rearrangements separate human chromosomes 12 and 22 and BTA5. Sequences analyzed from the telomeric region of BTA5 were found to be homologous with a single region of human chromosome 22. This region contains the gene encoding platelet derived growth factor B (PDGFB) which influences myofibroblast growth in mice and is a candidate gene for the QTL affecting growth and tenderness in cattle.