Why Small Dogs Are Small

Small Dogs

Soon after humans began domesticating dogs 12,000 to 15,000 years ago, they started breeding small canines. Now, scientists from the University of Utah and seven other institutions have identified a piece of doggy DNA that reduces the activity of a growth gene, ensuring that small breeds stay small.

The small piece of DNA is not a gene, but is known as a regulatory sequence. It is located on dog chromosome 15 next to a previously known gene named IGF1, for insulin-like growth factor 1. The gene and regulatory sequence together are known as a haplotype or variant, and that haplotype was found in all breeds of small dogs, showing it "is a major contributor to body size in all small dogs," the research team reports in the Friday, April 6 issue of the journal Science. The study is featured on Science's cover.

The scientists have not yet pinpointed the exact mutation in the regulatory DNA that reduces the IGF1 gene's output of a growth-inducing protein hormone. But finding the short stretch of DNA that keeps small dogs small serves as a model for how to track down genetic causes of complex, multigene traits, including human diseases such as heart disease, diabetes, arthritis and cancer, say study co-authors K. Gordon Lark and Kevin Chase, biologists at the University of Utah.

The IGF1 gene's hormone helps humans and other mammals grow from birth to adolescence. But in small dogs, one or more mutations in the DNA next to the IGF1 gene suppress the gene's activity, keeping small dogs from growing larger, says Lark, a distinguished professor emeritus of biology.

Medium and large dogs also have the IGF1 gene, but they do not have the same piece of DNA next to it, so their size is not restricted by that DNA, says Chase, a biology research specialist. Other yet-unidentified genes likely play a role in controlling the size of medium and large dogs, he adds.

Lark and Chase are among 21 authors of the new study, which was led by geneticists Elaine Ostrander and Nathan B. Sutter at the National Human Genome Research Institute, which is one of the National Institutes of Health in Bethesda, Md.