How Big Is The HD Population? - from Horizon #100, Spring 2001

“Population genetics” is the study of variation in natural populations. It has been used to examine questions ranging from the origins of humans to the evolution of the AIDS virus. Now researchers at the University of British Columbia and Kyushu University in Japan have applied ideas inspired by population genetics to the challenge of understanding the occurrence of Huntington disease.

Using a new mathematical model to measure “mutational flow”, Dr. Daniel Falush and his colleagues have concluded that new mutations in the Huntington’s gene occur more frequently than has been suspected until now.

“Approximately 10% of individuals who develop clinical disease,” says Dr. Daniel Falush, “have parents who, on the basis of their own health history, would not have been considered to be carriers of HD.”

Working in collaboration with Dr. Michael Hayden and his research group, Dr. Falush also suggests in the February 2001 issue of the American Journal of Human Genetics that current estimates of the size of the HD population are probably too low. The difficulties of recognizing the disease in individuals with fewer than 44 CAG repeats — largely because of the likelihood of late onset — have led to “systematic underascertainment”.

The investigators conclude that “clinicians should not assume that HD is rare outside families known to be affected or that most cases have onset at under 50 years of age.” — RM/DF

See D. Falush, E. Almqvist, R. Brinkman, Y. Iwasa, and M. Hayden (2001). Measurement of mutational flow implies both a high new-mutation rate for Huntington disease and substantial underascertainment of late-onset cases. Am J Hum Genet 68:373-385.