NEW YORK (GenomeWeb News) – Members of the Horse Genome Project reported today in Science that they have completed a high quality draft genome for the domestic horse Equus caballus. The work stems from a decade-long international collaboration with about three years devoted to horse genome sequencing, assembly, and annotation.
The team used Sanger sequencing to tackle the genome of a Thoroughbred mare named Twilight, generating a draft sequence that covers more than 95 percent of the horse genome at nearly seven times coverage. The genome is already proving useful for comparative genomic and population studies of the horse. And, researchers say, it contains hints that will likely be valuable for future studies of horse — and human — diseases.
The researchers selected the mare from Cornell Medical School's research herd because they expected her to be somewhat more inbred than horses from other breeds, senior author Kerstin Lindblad-Toh, a comparative genomics researcher at Uppsala University and scientific director of vertebrate genome biology at the Broad Institute, told GenomeWeb Daily News.
Using Sanger sequencing, the team generated 2.5 to 2.7 gigabases of sequence data covering more than 95 percent of the horse genome to about 6.8 times depth.
Their subsequent analyses suggest the horse genome is highly repetitive: 46 percent of the assembly contains repetitive sequences.
In contrast, less than one percent of the genome is comprised of segmental duplications. Likewise, the genome contained relatively few large rearrangements. In fact, the team found that more than half of horse chromosomes — 17 of 32 — are completely syntenic with human chromosomes.
They predict the genome contains 20,322 protein-coding genes, including more than 16,600 human gene orthologues. Gene families that have undergone expansion in the horse include keratin and opsin genes, which the researchers speculated might relate to processes such as hoof formation and visual perception, respectively.
The team was also intrigued to find a centromere on chromosome 11 missing the repeats usually present in mature centromeres, Lindblad-Toh noted. Based on their subsequent experiments, they concluded that the centromere had formed before the repeat sequences normally associated with centromeres and was evolutionarily new.
"We don't know a lot about centromeres, particularly because they have proven so difficult to analyze by DNA sequencing," lead author Claire Wade, formerly of the Broad Institute and now a researcher at the University of Sydney, said in a statement. "This result helps address some important questions about how centromeres evolve."
And since some cancer cells seem to contain newly formed centromeres, Lindblad-Toh added, understanding centromere formation may eventually inform some human cancer studies.
She and her colleagues say the horse genome holds information that could be useful for understanding other human diseases too. Since horses get a range of conditions that resemble human health problems such as inflammatory disease, infertility, and muscle disorders, the team explained, horses could be useful for modeling such conditions.
"Horses and humans suffer from similar illnesses, so identifying the genetic culprits in horses promises to deepen our knowledge of disease in both organisms," Lindblad-Toh said in a statement.
By genotyping about 1,000 SNPs in a dozen horse populations, the researchers have already started unraveling haplotype and genetic diversity patterns between horse breeds that could aid such studies.
And in a preliminary proof-of-principle study, the team used their million marker SNP map — developed through comparisons of several different horse breeds, including Thoroughbreds, American quarter horses, Andalusians, Arabians, Belgian draft horses, Hanoverians, Hakkaido, Icelandic horses, Norwegian fjord horses, and Standardbreds — to find dozens of SNPs linked to a "Appaloosa spotting," a white spotting pattern that frequently occurs in horses that also have night blindness.
"Our results demonstrate that horse population history has led to across-breed haplotype sharing, increasing the feasibility of across-breed mapping," the team concluded. "Mapping projects in the horse are likely to accelerate in the coming years and will identify mutations in genes related to morphology, immunology, and metabolism, which may benefit human health."