Final Activity Report Summary - BEEFGENES (Exploring genome organisation at QTLs for beef production traits at high resolution to identify candidate genes)
The research undertaken through this Marie-Curie Fellowship concerned the exploration of regions of the cattle genome controlling beef production traits, i.e. quantitative trait loci (QTL) for beef production traits. The aim of the project was to characterise some previously identified QTL affecting meat quality traits (e.g. meat tenderness, meat chemical composition) and classical beef production traits (carcass yield and carcass composition related traits) in order to identify candidates for the genes underlying the observed QTL effects. The resource population where the QTL were initially identified was an experimental cattle population established at the Roslin Institute by crossing Charolais sires (a specialised beef breed) and Holstein dams (a specialised dairy breed). The GemQual population, which comprised 50 individuals of 15 different breeds part analysed in a previous European funded project), was studied at the final stage trying to address the limits on the genetic resolution in the RoBoGen population arising from the extensive linkage disequilibrium in this population.
The first step of the research consisted of the analysis of new markers across the whole population in order to better define the regions harbouring the QTL. The availability of the first draft sequence of the bovine genome allowed the identification of new markers from in silico analyses. The inclusion of the new markers in the analysis led to a considerable reduction of, and hence improvement in the QTL confidence interval, allowing the identification of positional candidate genes in the studied regions. Among the positional candidates, those genes whose known biological function suggested a possible relation with the QTL effect were selected for further studies. Examples of candidate genes identified are SPP1, ABCG2, PPARCG1A, IBSP on chromosome 6, IGF-1 and SOCS2 on chromosome 5, CAPN1 on chromosome 29, etc.
A search for allelic variants (mainly single nucleotide polymorphisms, SNPs) in the strong candidates was performed from publicly available resources (literature, NCBI, Ensembl Browser) and from information derived from the GemQual project. Both populations, RoBoGen and GemQual, were genotyped for about 70 SNP markers.
The SNP information was subsequently included in the QTL analysis of the RoBoGen population. The conclusion from these analyses was that none of the analysed SNPs explained the QTL effects and thus could be eliminated as candidates for the causal genetic variation. However, the use of these mutations as markers in the linkage analysis together with some additional microsatellite markers, again allowed a substantial reduction of the QTL confidence interval. The high level of information currently being derived from the bovine genome sequence and annotation projects will speed up the identification of the causal mutation in the QTL regions narrowed by this project. Additional markers genotyped in the final period of the Fellowship are being currently analysed.
As the RoBoGen population had also been characterised for a range of other traits in addition to the beef traits other analyses were performed in order to map QTL influence these other phenotypic traits (e.g. coat colour features, temperament traits, and meat fatty acid composition).
The first step of the research consisted of the analysis of new markers across the whole population in order to better define the regions harbouring the QTL. The availability of the first draft sequence of the bovine genome allowed the identification of new markers from in silico analyses. The inclusion of the new markers in the analysis led to a considerable reduction of, and hence improvement in the QTL confidence interval, allowing the identification of positional candidate genes in the studied regions. Among the positional candidates, those genes whose known biological function suggested a possible relation with the QTL effect were selected for further studies. Examples of candidate genes identified are SPP1, ABCG2, PPARCG1A, IBSP on chromosome 6, IGF-1 and SOCS2 on chromosome 5, CAPN1 on chromosome 29, etc.
A search for allelic variants (mainly single nucleotide polymorphisms, SNPs) in the strong candidates was performed from publicly available resources (literature, NCBI, Ensembl Browser) and from information derived from the GemQual project. Both populations, RoBoGen and GemQual, were genotyped for about 70 SNP markers.
The SNP information was subsequently included in the QTL analysis of the RoBoGen population. The conclusion from these analyses was that none of the analysed SNPs explained the QTL effects and thus could be eliminated as candidates for the causal genetic variation. However, the use of these mutations as markers in the linkage analysis together with some additional microsatellite markers, again allowed a substantial reduction of the QTL confidence interval. The high level of information currently being derived from the bovine genome sequence and annotation projects will speed up the identification of the causal mutation in the QTL regions narrowed by this project. Additional markers genotyped in the final period of the Fellowship are being currently analysed.
As the RoBoGen population had also been characterised for a range of other traits in addition to the beef traits other analyses were performed in order to map QTL influence these other phenotypic traits (e.g. coat colour features, temperament traits, and meat fatty acid composition).