Genetic Linkage Evidence for a Familial Alzheimer's Disease Locus on Chromosome 14

Gerard D. Schellenberg(University of Washington), Thomas D. Bird(Veterans Health Administration), Ellen M. Wijsman(University of Washington Medical Center), Harry T. Orr(University of Minnesota), Leojean Anderson(University of Washington), Ellen Nemens(University of Washington), June White(University of Minnesota), Lori L. Bonnycastle(University of Washington), James L. Weber(Marshfield Clinic), María Elisa Alonso(Instituto Nacional de Neurología y Neurocirugía), Huntington Potter(Harvard University), Leonard L. Heston(Mental Illness Research, Education and Clinical Centers), George M. Martin(University of Washington)
Science
October 23, 1992
10.1126/science.1411576
Cited by 945

Abstract

Linkage analysis was used to search the genome for chromosomal regions harboring familial Alzheimer's disease genes. Markers on chromosome 14 gave highly significant positive lod scores in early-onset non-Volga German kindreds; a Zmax of 9.15 (theta = 0.01) was obtained with the marker D14S43 at 14q24.3. One early-onset family yielded a lod score of 4.89 (theta = 0.0). When no assumptions were made about age-dependent penetrance, significant results were still obtained (Zmax = 5.94, theta = 0.0), despite the loss of power to detect linkage under these conditions. Results for the Volga German families were either negative or nonsignificant for markers in this region. Thus, evidence indicates a familial Alzheimer's disease locus on chromosome 14.

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