Proposal to sequence the genome of the domestic horse, Equus caballus

I. Introduction and Rationale for the Project We are applying to National Human Genome Research Institute (NHGRI) for funding to produce a draft-2X reference sequence for the genome of the horse that can be integrated with physical and genetic maps. A whole genome shotgun approach is ideal for this approximately 2.5-3.0 billion base pair genome since preliminary data suggests that the genome is not highly repetitive and that most repeats are sufficiently diverged to ensure a random representation and low level assembly of the whole genome with this approach. The fosmid library produced from the reference horse in connection with the shotgun sequencing procedure will also be a valuable tool for the applications described below. Another important part of the project should be discovery of single nucleotide polymorphisms (SNPs) generated by conducting further low coverage sequencing of horses from diverse breeds. These SNPs will be essential for investigations using haplotypes in horse populations with well-recorded, deep pedigrees and other quantitative trait loci (QTL) studies. Main points supporting inclusion of the horse among NHGRI-supported mammals with low-coverage full genome sequencing include: 1. The horse is proposed as the representative species of the order Perissodactyla. No other species from this order have yet been sequenced. The order includes both domesticated and wild species, some of which are highly endangered. Investigations of the horse genera have been especially important in evolutionary biology, particularly for the well-preserved fossil record and the karyotypic evidence of rapid chromosomal rearrangements for the genus Equus (MacFadden, 2005). 2. A distinguishing characteristic of the horse compared to other reference animals is its extensive breeding records. Horse breeders have maintained meticulous pedigree records for many horse breeds, some extending back over 300 years. Deep pedigree records coupled with excellent health and performance records provides excellent material for (QTL) studies. The cooperation of horse breeders with participants in the horse genome workshop has been excellent. 3. An organized international community of basic research scientists and veterinary clinicians work in the area of horse genetics. Scientists from over 25 laboratories meet regularly and have been collaborating on equine genome definition and application for the past decade. The major forums for meetings have been in connection with the USDA-NRSP8 program, the International Society for Animal Genetics and the Dorothy Russell Havemeyer Foundation Workshops on horse genomics. More than 150 multi-institutional publications have resulted from these collaborations. 4. Comparison with other mammalian genomes will …