Our aim was to determine if the high frequency of metachromatic leukodystrophy (MLD) in Navajo Indians of the Southwestern United States is the result of a "genetic bottleneck" that occurred in the mid 19th century. Navajo Nation, Indian Health Service, and other national databases were queried for Native American patients with MLD. Pedigrees, including birth location, were established by interviewing relatives. We found that cases of MLD and their ancestors are clustered in a portion of the western Navajo Nation to which a small number of Navajo fled after armed conflict with the United States Army in the 1860s. The observed incidence of MLD on the western Navajo Nation is 1/2,520 live births, with an estimated carrier frequency of 1/25 to 1/50. No cases were observed in the eastern part of the Navajo Nation over a period of 18 years (60,000 births). The high incidence of MLD in the western Navajo Nation appears to be the result of a genetic bottleneck and probable founder effect from the mid 19th century: This mechanism may also explain the high incidence of a number of other unique, heritable disorders among the Navajo. The history of the Navajo may also be relevant to other American Indian and Alaskan Native groups that have undergone severe population reduction since the arrival of Europeans in North America.
Copyright 2001 Wiley-Liss, Inc.