Linkage of a Gene Causing Familial Amyotrophic Lateral Sclerosis to Chromosome 21 and Evidence of Genetic-Locus Heterogeneity

Abstract

The localization of a gene causing familial amyotrophic lateral sclerosis provides a means of isolating this gene and studying its function. Insight gained from understanding the function of this gene may be applicable to the design of rational therapy for both the familial and sporadic forms of the disease.

Mutational analysis of the Cu/Zn superoxide dismutase gene in 23 familial and 69 sporadic cases of amyotrophic lateral sclerosis in Belgium

“…12 A mutation in the SOD1 gene in seven of 11 Belgian families (64%) is a high figure, compared with other previously published, larger studies, eg 13% in Canada or 20% in the UK, 13,14 but it is closer to the 50% in the Scottish series 15 and in agreement with the results of the original linkage analysis whereby in 55% of the FALS families linkage to markers on chromosome 21 was found. 16 The most common mutation in the US, A4V, was not found in the Belgian population. 17 L38V and G93C have not (yet) been detected in other populations.…”

A mathematically designed STS primer without any mismatches for direct sequencing of cosmid DNA clones

“…Human chromosomes have been well characterized genetically as part of an effort to identify the many genes that are potentially involved in important inherited disorders (Scoggin and Patterson, 1982;Siddique et al, 1991;St. George-Hyslop et al, 1987).…”

Decreased Intracellular Superoxide Levels Activate Sindbis Virus-induced Apoptosis

“…Moreover, genetic studies indicate that inherited mutations in antioxidant defenses may also induce neuropathology (29,30). For example, a subset of patients with a familial form of amyotrophic lateral sclerosis have been found to carry mutations in the gene encoding the antioxidant enzyme, copper/zinc superoxide dismutase (Cu,Zn-SOD) (29,31,32). Mutations in the Cu,Zn-SOD gene appear to diminish the threshold for activation of apoptosis in neurons, and antioxidants can restore the threshold for activation of cell death to levels seen in cells carrying wild type Cu,Zn-SOD (33).…”