Linkage analysis in familial amyotrophic lateral sclerosis

T. Siddique*, M. A. Pericak-Vance, B. R. Brooks, R. P. Roos, W. Y. Hung, J. P. Antel, T. L. Munsat, K. Phillips, K. Warner, M. Speer, W. B. Bias, N. A. Siddique, A. D. Roses

*Corresponding author for this work

Research output: Contribution to journalArticle

57 Scopus citations

Abstract

Familial amyotrophic lateral sclerosis (FALS) constitutes 5 to 10% of cases of ALS and, in most families, ite inheritance is consistent with an autoeomal dominant trait with age-dependent penetrance. The biochemical abnormality underlying the disorder is unknown. We analyzed DNA from 131 members of 6 multigenerational ALS families, which included 13 affected members, for genetic linkage to 39 expreased and DNA markers, using the techniques of 2-point linkage analysis, multilocus linkage analysis, and exclusion mapping. We identified FALS families with structures suitable for linkage, by computer simulation techniques. A DNA bank established to provide optimum use of available FALS families provided DNA from immortalized lymphobht cell lines and frozen postmortem tissue. We could not link FALS to any of the markers studied, but excluded chromosome regions unlikely to be a locus of the FALS gene. With the help of this exclusion data, we will concentrate on regions of the human genome that remain unexcluded.

Original languageEnglish (US)
Pages (from-to)919-925
Number of pages7
JournalNeurology
Volume39
Issue number7
DOIs
StatePublished - Jul 1989

ASJC Scopus subject areas

  • Clinical Neurology

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    Siddique, T., Pericak-Vance, M. A., Brooks, B. R., Roos, R. P., Hung, W. Y., Antel, J. P., Munsat, T. L., Phillips, K., Warner, K., Speer, M., Bias, W. B., Siddique, N. A., & Roses, A. D. (1989). Linkage analysis in familial amyotrophic lateral sclerosis. Neurology, 39(7), 919-925. https://doi.org/10.1212/wnl.39.7.919