Gene Variation Is Responsible for Dog Sizes

Investigators have found that variation in one gene--IGF-1, which codes for a protein hormone called insulin-like growth factor 1, is very strongly associated with small stature across different dog breeds

In their study, scientists explored the genetic basis for size variation among dogs by comparing the DNA of various small dog breeds, including Chihuahuas, Toy Fox Terriers, and Pomeranians, to an array of larger dog breeds, including Irish Wolfhounds, Saint Bernards, and Great Danes. The branch of the canine family tree that includes domestic dogs diverged from that of the gray wolf more than 15,000 years ago. Due to selective breeding by humans throughout history, dogs today exhibit an extremely wide range of body types and behaviors. In fact, dogs exhibit the greatest diversity in body size of any mammalian species.

An international team led by scientists from the U.S. National Human Genome Research Institute (NHGRI; Bethesda, MD, USA), part of the U.S. National Institutes of Health (NIH; Bethesda, MD, USA), identified the genetic variant that is the major contributor to small size in dogs. The findings appear in the April 6, 2007, issue of the journal Science.

The identification and characterization of a key genetic variant that accounts for differences in dog size is particularly exciting because the underlying gene is present in all dogs and other diverse species, including humans, said Eric Green, M.D., Ph.D., scientific director of the NHGRI Division of Intramural Research. Discoveries like this illustrate the exciting promise of genomics research for understanding the inheritance of a wide range of traits, including those that have an impact on health and disease.

We have been intrigued by the population structure of dogs, which over the years have been selectively bred, allowing us to more readily analyze the genetic causes of particular traits than is possible in humans, said the study's senior author, Elaine A. Ostrander, Ph.D., chief of NHGRI's Cancer Genetics Branch. Nearly all of what we learn from studying body structure, behavior, and disease susceptibility in dogs helps us understand some aspect of human health and biology.

The researchers analyzed DNA from more than 3,000 dogs from 143 breeds to pinpoint a specific gene sequence variant, or haplotype, associated with small size in the canine genetic code. Nearly all of the small dogs studied shared this genetic variant, implicating it as a major influence on stature in dogs.

Based on their genomic analysis, the researchers also concluded that the small size trait emerged relatively early in the history of domestic dogs. They hypothesize that small size may have facilitated the rapid diversification among domestic dog breeds by making it easier for humans to maintain them in the crowded confines of developing villages and cities, as well as making them more transportable during trade and migration.

By learning how genes control body size in dogs, we are apt to learn something about how skeletal body size is genetically programmed in humans. We also will increase our data set of genes likely to play a role in diseases such as cancer, in which regulation of cell growth has been lost, said Dr. Ostrander, noting that the role of the IGF-1 gene family in prostate cancer susceptibility has already been well established.


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