The objective of the present proposal is to evaluate a novel method for the genetic fine-mapping of Quantitative Trait Loci (QTL) underlying economically important traits, in livestock, based on within-and across-breed identity-by-descent (IBD).
Major efforts are presently being devoted to the genetic mapping of QTL underlying production traits in the different livestock species. Results of the first whole genome scans in pigs (Andersson et al., Science, 263:1771-1774, 1994) and cattle (Georges et al., Genet;cs 139:907-920, 1995) convincingly demonstrate that tbis endeavours will very likely be succesful and yield a large number of mapped loci in the near future. This opens the way towards the exploitation of these results in more efficient Marker Assisted Selection schemes, another intense area of animal science research. The increasing palticipation of the concerned industries in these projects testifies of their growing interest in what is likely to become a indispensable tool in future breeding programs aimed at increasing the efficiency of animal production.
Efficient utilisation of the mapped QTL in breeding programs, however, as well as the ultimate positional cloning of the corresponding genes, requires a higher mapping resolution than what is presently being achieved. Within the constraints of the present experimental designs, Quantitative Trait Loci (QTL) are often mapped to support intervals that are several tens of centimorgan large, corresponding to several tens of millions of base pairs and several hundreds if not thousands of possible candidate genes.
To overcome the resolution limits of the present QTL mapping methods, we therefore propose to evaluate a novel strategy to fine-map QTL segregating in outbred populations. The proposed strategy exploits the identity-by-descent of QTL alleles with large substitution effects, both within- and across-breeds. The within-breed component of ther project assumes that QTL alleles with large effects are often genetically homogeneous or IBD within breeds. These IBD QTL alleles are expected to be flanked by an IBD chromosome segment, of a size that will reflect the number of generations to a common ancestor or coalescence . The across-breed component assumes that different breeds share IBD QTL alleles that have migrated between these breeds where they have been maintained by artificial selection. Likewise, across-breed IBD QTL alleles are expected to be flanked by IBD chromosome segments, of a size that will reflect the number of generations to a common ancestor or coalescence . The number of generations to coalescence is expected to be higher in the across-breed approach, therefore allowing for a superior mapping resolution. Identifying such IBD segment in chromosomal areas where conventional QTL mapping strategies have shown evidence for QTL, would unambiguously map the QTL at a reslution that would be extremely difficult and costly to achieve using conventional strategies.
This strategy therefore proposes to take advantage of the breed diversity characterizing the European (and potentially other) continents and is a concrete justification of the programs aimed at the conservation of livestock biodiversity.
The specific objective of the EURIBMS project is the evaluation of the efficacy of the proposed QTL fine-mapping method in a pilot experiment focusing on a QTL with major effect on milk yield and composition mapping to bovine chromosome 6 (Georges et al., Genetics 139:907-920, 1995). The choice of this QTL was dictated because (i) the genuine nature of this QTL has been confirmed in several independent studies (ref.), (ii) the QTL has a major effect on the studied traits which facilitates the identification of segregating sire-families, and (iii) it is the only QTL to date that has been shown to segregate in different breeds (ref.). The partnership reatizes that the traits that are affected by this QTL are economically not the most relevant ones for application of MAS. This project is meant as an evaluation of the proposed method, that if succesful will be applicable to QTL affecting other traits. All partners are actively involved in mapping QTL affecting production efficiency, product quality and disease resistance in cattle.
This project will yield a high resolution genetic and physical map of the corresponding region on bovine chromosome 6.