Horse genome sequence and analysis published in Science

November 05, 2009

An international team of researchers has decoded the genome of the domestic horse Equus caballus, revealing a genome structure with remarkable similarities to humans and more than one million genetic differences across a variety of horse breeds. In addition to shedding light on a key part of the mammalian branch of the evolutionary tree, the work also provides a critical starting point for mapping disease genes in horses.

"Horses and humans suffer from similar illnesses, so identifying the genetic culprits in horses promises to deepen our knowledge of disease in both organisms," said senior author Kerstin Lindblad-Toh, scientific director of vertebrate genome biology at the Broad Institute of MIT and Harvard and a professor of comparative genomics at Uppsala University in Sweden. "The horse genome sequence is a key enabling resource toward this goal."

For centuries, horses have been close human companions. The animals were first domesticated 4,000 to 6,000 years ago and were harnessed primarily for power and transportation. Over time, as machines have become the chief sources of agricultural and industrial muscle, those roles have shifted to mainly sports and recreational activities.

Predating this coexistence, humans and horses share an evolutionary history that has implications for the health of both species. Like other mammals, the two species share much of the same DNA. Moreover, horses suffer from more than 90 hereditary diseases that show similarities to those in humans. Recognizing the need for genomic tools to foster biomedical research on horses as well as humans, a research consortium led by scientists at the Broad Institute of MIT and Harvard launched a project three years ago to decode the horse's genetic blueprint. The effort was based on a ten-year collaboration among an international group of scientists to exploit genomic technologies for the benefit of equine health known as the Horse Genome Project.

"We are especially grateful to our collaborators in the horse genetics community who participated in this project," said Lindblad-Toh. "We really could not have done this work without them."

To generate a high-quality genome sequence, the researchers analyzed DNA from an adult female Thoroughbred named Twilight. The horse's DNA was decoded using conventional capillary DNA sequencing technology (known as Sanger sequencing) to reveal a genome that is roughly 2.7 billion letters, or nucleotides, in size -- slightly larger than the genome of the domestic dog, and smaller than both the human and cow genomes.

A remarkable feature of the horse genome is the small number of chromosomal rearrangements that have occurred in horses relative to humans. During the course of evolution, parts of chromosomes can get shuffled to other locations in the genome, or they can remain in their original ancestral order, like beads on a string -- a situation known as "synteny." More than half of the horse chromosomes show synteny with a single human chromosome. This is in contrast to dogs, where the figure is less than one-third.

Another intriguing result to emerge from the horse genome analysis pertains to chromosomes and something called the "centromere." If you imagine chromosomes as X-shaped, centromeres are the central constrictions where the arms of the 'X' come together.

More than just a nexus, centromeres ensure that cells inherit copies of each chromosome during cellular division. Despite this essential role, relatively little is known about them. It is clear that they contain highly repetitive DNA sequences, but what is less clear is which comes first, the centromere or its repeats.

Lindblad-Toh and her colleagues, including Elena Giulotto of Pavia University in Italy, were surprised to uncover a region on horse chromosome 11 that contains a developing centromere, already functional, but frozen in a young state. Analyses of this budding centromere revealed no repetitive DNA, suggesting that centromeres appear first and their repeats appear later

"We don't know a lot about centromeres, particularly because they have proven so difficult to analyze by DNA sequencing," said first author Claire Wade, a former researcher at the Broad Institute and the Center for Human Genetic Research at Massachusetts General Hospital who is now a professor at the University of Sydney in Australia. "This result helps address some important questions about how centromeres evolve."

In addition to sequencing the genome of a Thoroughbred horse, the researchers also examined DNA from a variety of other horse breeds, including the American quarter horse, Andalusian, Arabian, Belgian draft horse, Hanoverian, Hakkaido, Icelandic horse, Norwegian fjord horse, and Standardbred breeds. The team surveyed the extent of genetic variation both within and across breeds to create a catalog of more than one million single-letter genetic differences (called "single nucleotide polymorphisms" or SNPs).

In a first proof-of-principle of the power of trait mapping in horses, the researchers harnessed the SNP catalog to localize the candidate mutation in the Leopard Complex or "Appaloosa spotting," in which horses' coats are mottled with striking patches of white, either with or without colored spots. Horses carrying this trait often suffer from a form of night blindness, a disorder that also afflicts humans. The researchers narrowed the list of genetic suspects in horses to 42 associated SNPs, including two candidate mutations residing near a gene involved in pigmentation.

"This demonstrates the utility of the horse for disease gene mapping," said Wade. "By making these resources freely available to the scientific community, we hope that many new results will flow from them in the coming years."
-end-
The research was funded by the National Human Genome Research Institute as well as the Dorothy Russell Havemeyer Foundation, the Volkswagen Foundation, the Morris Animal Foundation and the Programmi di Ricerca Scientifica di Rilevante Interesse Nazionale.

Paper cited:

Wade et al. Genome sequence, comparative analysis, and population genetics of the domestic horse. Science DOI: 10.1126/science.1178158

A full list of authors and collaborating institutions can be found on the journal's website.

About the Broad Institute of MIT and Harvard

The Eli and Edythe L. Broad Institute of MIT and Harvard was founded in 2003 to empower this generation of creative scientists to transform medicine with new genome-based knowledge. The Broad Institute seeks to describe all the molecular components of life and their connections; discover the molecular basis of major human diseases; develop effective new approaches to diagnostics and therapeutics; and disseminate discoveries, tools, methods and data openly to the entire scientific community.

Founded by MIT, Harvard and its affiliated hospitals, and the visionary Los Angeles philanthropists Eli and Edythe L. Broad, the Broad Institute includes faculty, professional staff and students from throughout the MIT and Harvard biomedical research communities and beyond, with collaborations spanning over a hundred private and public institutions in more than 40 countries worldwide. For further information about the Broad Institute, go to www.broadinstitute.org.

Broad Institute of MIT and Harvard

Related DNA Articles from Brightsurf:

A new twist on DNA origami
A team* of scientists from ASU and Shanghai Jiao Tong University (SJTU) led by Hao Yan, ASU's Milton Glick Professor in the School of Molecular Sciences, and director of the ASU Biodesign Institute's Center for Molecular Design and Biomimetics, has just announced the creation of a new type of meta-DNA structures that will open up the fields of optoelectronics (including information storage and encryption) as well as synthetic biology.

Solving a DNA mystery
''A watched pot never boils,'' as the saying goes, but that was not the case for UC Santa Barbara researchers watching a ''pot'' of liquids formed from DNA.

Junk DNA might be really, really useful for biocomputing
When you don't understand how things work, it's not unusual to think of them as just plain old junk.

Designing DNA from scratch: Engineering the functions of micrometer-sized DNA droplets
Scientists at Tokyo Institute of Technology (Tokyo Tech) have constructed ''DNA droplets'' comprising designed DNA nanostructures.

Does DNA in the water tell us how many fish are there?
Researchers have developed a new non-invasive method to count individual fish by measuring the concentration of environmental DNA in the water, which could be applied for quantitative monitoring of aquatic ecosystems.

Zigzag DNA
How the cell organizes DNA into tightly packed chromosomes. Nature publication by Delft University of Technology and EMBL Heidelberg.

Scientists now know what DNA's chaperone looks like
Researchers have discovered the structure of the FACT protein -- a mysterious protein central to the functioning of DNA.

DNA is like everything else: it's not what you have, but how you use it
A new paradigm for reading out genetic information in DNA is described by Dr.

A new spin on DNA
For decades, researchers have chased ways to study biological machines.

From face to DNA: New method aims to improve match between DNA sample and face database
Predicting what someone's face looks like based on a DNA sample remains a hard nut to crack for science.

Read More: DNA News and DNA Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.