July/August 2007

Guide Dogs

By sequencing the dog genome, the Broad Institute has accelerated the search for mutations involved in human diseases. Now a push to sequence more mammals may reveal how our own genome works.

By Katherine Bourzac, SM '04

Credit: Bob O’Connor

Multimedia •  View images of the Broad Insitute and their work.

The ideal boxer dog is strong, squarely built, smooth. Breeders prize it for its chiseled head. "The beauty of the head depends upon the harmonious proportion of muzzle to skull," read the American Kennel Club's standards for the breed. "The blunt muzzle is one third the length of the head from the occiput to the tip of the nose, and two thirds the width of the skull." Intelligent and alert, a boxer conveys grace with every movement.

The structure of the genome underlying the boxer's graceful build is also "gorgeous," says ­Kerstin Lindblad-Toh, the molecular biologist who led the effort to sequence the dog genome. As codirector of the program in genome sequencing and analysis at the Broad Institute for genomic medicine, Lindblad-Toh has also overseen projects involving the mouse and the opossum, so she's well qualified to assess the boxer's genomic beauty. The source of that beauty is a relative lack of genetic diversity, the result of a hundred years of tightly controlled breeding for traits like harmoniously proportioned skulls. The genetic homogeneity within dog breeds, and the narrowness of the differences between them, mean the dog genome holds valuable clues to the causes of common diseases in both dogs and humans.

The dog genome is about 2.4 billion bases long, but ­Lindblad-­Toh's group was able to sequence it in just six months. The Broad Institute, jointly run by MIT and ­Harvard University, is a genetic powerhouse, able to sequence 60 billion bases (the letters in the genomic alphabet) with 99 percent accuracy each year--the equivalent of several Human Genome Projects. It has a greater sequencing capacity than nearly any other public or academic facility in the world.

Today, much of that capacity is allocated to the Broad's mammalian-genome project. The Broad is one of three research centers funded by the National Institutes of Health in a major effort to bring the number of mammals whose genomes have been sequenced up to around 30 within the next few years. (The other two centers are at the Baylor College of Medicine in Houston and the Washington University School of Medicine in St. Louis.) Lindblad-Toh is overseeing sequencing and analysis projects for more than 20 animals at the Broad, providing resources for researchers who rely on animal models when studying human diseases. Her team's efforts will shed more light on how our own genome is regulated and fill in gaps in our understanding of human evolutionary history. Ultimately, this work could help answer some compelling questions: What makes a mammal a mammal, a primate a primate--and what makes us human?