WALTEX · Positional cloning of the gene causing the muscular hypertrophy of Texel sheep

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Project objective

Belgian Texel sheep are characterized by an inherited muscular hypertrophy, controlled by a major locus mapped to the pericentric region of sheep chromosome 2. The purpose of this project is to identify the corresponding gene and mutation. Knowledge of t his gene will allow for more effective marker assisted selection, will open possibilities for targeted development of drugs that could be useful in the treatment of muscle wasting, and will identify a potential target for engineering using transgenic te chniques. Identification of the causal gene and mutation will be achieved by means of positional cloning. To that end we will first improve the genetic and comparative map of the region. Bovine BAC libraries will be screened with available microsatellit es in the region of interest. Fingerprinting contigs (FPC) including the positive BACs will be identified by searching the ICE database compiled by the Genome Sequence Centre, Vancouver, Canada (http://www.bcgsc.bc.ca/). Novel microsatellites will be iso lated from the corresponding BACs. BAG ends will be sequenced and BLAST searches will be performed against the human genomic sequences to identify orthologous anchorpoints. BAC ends corresponding to the extremities of FPC will be used as probes to scree n the BAG libraries, thereby completing the contig of the region by \\\FPC walking\\\". Genetic fine-mapping will be accomplished with the new markers by exploiting linkage in the available F2 pedigree, and by exploiting linkage disequilibrium analysis within the Belgian Texel population (all double-muscled Belgian Texel are expected to share a common haplotype spanning the causal gene). We will identify (b)ovine cDNAs orthologous to the genes mapping to the corresponding human region using the EGO d atabase available from TIGR (http://www.tigr.org/), and assemble spotted cDNA microarrays including all these positional candidates."

Original text from CORDIS.

Participants

• UNIVERSITE DE LIEGE · LIEGECoordinatorBelgium

Links

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