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Hosler, B A; Siddique, T; Sapp, P C; Sailor, W; Huang, M C; Hossain, A; Daube, J R; Nance, M; Fan, C; Kaplan, J; Hung, W Y; McKenna-Yasek, D; Haines, J L; Pericak-Vance, M A; Horvitz, H R; Brown, Jr, R H
JAMA, 10/2000, Letnik: 284, Številka: 13Journal Article
Occasionally, 2 or more major neurodegenerative diseases arise simultaneously. An understanding of the genetic bases of combined disorders, such as amyotrophic lateral sclerosis (ALS) with frontotemporal dementia (FTD), will likely provide insight into mechanisms of these and related neurodegenerative diseases. To identify loci that contain genes whose defects cause ALS. A genome-wide linkage analysis of 2 data sets from an ongoing study begun in the mid-1980s at 4 university research centers. An initial subset of 16 families (549 people) potentially informative for genetic analysis, in which 2 or more individuals were diagnosed as having ALS, identified from a Boston data set of 400 families and 4 families potentially informative (244 people) subsequently identified from a Chicago data set of more than 300 families to test a hypothesis based on findings from the Boston families. Linkage calculations assuming autosomal dominant inheritance with age-dependent penetrance (a parametric logarithm-of-odds lod score of 1.0 or greater required for further study of a potential locus); crossover analysis involving the ALS-FTD locus. In a set of families in which persons develop both ALS and FTD or either ALS or FTD alone, a genetic locus that is linked to ALS with FTD located between markers D9S301 and D9S167 was identified on human chromosome 9q21-q22. Families with ALS alone did not show linkage to this locus. Crossover analysis indicates this region covers approximately 17 cM. These data suggest that a defective gene located in the chromosome 9q21-q22 region may be linked to ALS with FTD. JAMA. 2000;284:1664-1669.
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