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

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Research output: Contribution to journalArticle

339 Citations (Scopus)

Abstract

Background. Amyotrophic lateral sclerosis is a progressive neurologic disorder that commonly results in paralysis and death. Despite more than a century of research, no cause of, cure for, or means of preventing this disorder has been found. In a minority of cases, it is familial and inherited as an autosomal dominant trait with age-dependent penetrance. In contrast to the sporadic form of amyotrophic lateral sclerosis, the familial form provides the opportunity to use molecular genetic techniques to localize an inherited defect. Furthermore, such studies have the potential to discover the basic molecular defect causing motor-neuron degeneration. gene causing this disease to four DNA markers on the long arm of chromosome 21. Multipoint linkage analyses demonstrated linkage between the gene and these markers. The maximum lod score — 5.03 — was obtained 10 centimorgans distal (telomeric) to the DNA marker D21S58. There was a significant probability (P<0.0001 ) of genetic-locus heterogeneity in the families. 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. (N Engl J Med 1991; 324:1381–4.)

Original languageEnglish (US)
Pages (from-to)1381-1384
Number of pages4
JournalNew England Journal of Medicine
Volume324
Issue number20
DOIs
StatePublished - May 16 1991
Externally publishedYes

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Chromosomes, Human, Pair 21
Genetic Loci
Genetic Heterogeneity
Genes
Genetic Markers
Lod Score
Genetic Techniques
Nerve Degeneration
Penetrance
Amyotrophic Lateral Sclerosis
Motor Neurons
Nervous System Diseases
Paralysis
Molecular Biology
Amyotrophic lateral sclerosis 1
Research

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

@article{d0fb797f97ac4ef18b0ecacdfd00497b,
title = "Linkage of a Gene Causing Familial Amyotrophic Lateral Sclerosis to Chromosome 21 and Evidence of Genetic-Locus Heterogeneity",
abstract = "Background. Amyotrophic lateral sclerosis is a progressive neurologic disorder that commonly results in paralysis and death. Despite more than a century of research, no cause of, cure for, or means of preventing this disorder has been found. In a minority of cases, it is familial and inherited as an autosomal dominant trait with age-dependent penetrance. In contrast to the sporadic form of amyotrophic lateral sclerosis, the familial form provides the opportunity to use molecular genetic techniques to localize an inherited defect. Furthermore, such studies have the potential to discover the basic molecular defect causing motor-neuron degeneration. gene causing this disease to four DNA markers on the long arm of chromosome 21. Multipoint linkage analyses demonstrated linkage between the gene and these markers. The maximum lod score — 5.03 — was obtained 10 centimorgans distal (telomeric) to the DNA marker D21S58. There was a significant probability (P<0.0001 ) of genetic-locus heterogeneity in the families. 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. (N Engl J Med 1991; 324:1381–4.)",
author = "Collaborators and Teepu Siddique and Figlewigz, {Denise A.} and Pericak-Vance, {Margaret A.} and Haines, {Jonathan L.} and Guy Rouleau and Jeffers, {Anita J.} and Peter Sapp and Hung, {wu Yen} and Jacqueline Bebout and Diane Mckenna-Yasek and Gang Deng and Horvitz, {H. Robert} and Gusella, {James F.} and Brown, {Robert H.} and Roses, {Allen D.} and Roos, {Raymond P.} and Williams, {David B.} and Mulder, {Donald W.} and Watkins, {Paul C.} and Noore, {Faizur Rahman} and Garth Nicholson and Rosalyn Reed and Brooks, {Benjamin R.} and Barry Festoff and Antel, {Jack P.} and Rup Tandan and Munsat, {Theodore L.} and Laing, {Nigel G.} and John Halperin and Norris, {Forbes H.} and {Van den Bergh}, R. and Lorry Swerts and Tanzi, {Rudolph E.} and Burk Jubelt and Mathews, {Katherine D.} and Bosch, {E. Peter}",
year = "1991",
month = "5",
day = "16",
doi = "10.1056/NEJM199105163242001",
language = "English (US)",
volume = "324",
pages = "1381--1384",
journal = "New England Journal of Medicine",
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publisher = "Massachussetts Medical Society",
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}

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

In: New England Journal of Medicine, Vol. 324, No. 20, 16.05.1991, p. 1381-1384.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Linkage of a Gene Causing Familial Amyotrophic Lateral Sclerosis to Chromosome 21 and Evidence of Genetic-Locus Heterogeneity

AU - Collaborators

AU - Siddique, Teepu

AU - Figlewigz, Denise A.

AU - Pericak-Vance, Margaret A.

AU - Haines, Jonathan L.

AU - Rouleau, Guy

AU - Jeffers, Anita J.

AU - Sapp, Peter

AU - Hung, wu Yen

AU - Bebout, Jacqueline

AU - Mckenna-Yasek, Diane

AU - Deng, Gang

AU - Horvitz, H. Robert

AU - Gusella, James F.

AU - Brown, Robert H.

AU - Roses, Allen D.

AU - Roos, Raymond P.

AU - Williams, David B.

AU - Mulder, Donald W.

AU - Watkins, Paul C.

AU - Noore, Faizur Rahman

AU - Nicholson, Garth

AU - Reed, Rosalyn

AU - Brooks, Benjamin R.

AU - Festoff, Barry

AU - Antel, Jack P.

AU - Tandan, Rup

AU - Munsat, Theodore L.

AU - Laing, Nigel G.

AU - Halperin, John

AU - Norris, Forbes H.

AU - Van den Bergh, R.

AU - Swerts, Lorry

AU - Tanzi, Rudolph E.

AU - Jubelt, Burk

AU - Mathews, Katherine D.

AU - Bosch, E. Peter

PY - 1991/5/16

Y1 - 1991/5/16

N2 - Background. Amyotrophic lateral sclerosis is a progressive neurologic disorder that commonly results in paralysis and death. Despite more than a century of research, no cause of, cure for, or means of preventing this disorder has been found. In a minority of cases, it is familial and inherited as an autosomal dominant trait with age-dependent penetrance. In contrast to the sporadic form of amyotrophic lateral sclerosis, the familial form provides the opportunity to use molecular genetic techniques to localize an inherited defect. Furthermore, such studies have the potential to discover the basic molecular defect causing motor-neuron degeneration. gene causing this disease to four DNA markers on the long arm of chromosome 21. Multipoint linkage analyses demonstrated linkage between the gene and these markers. The maximum lod score — 5.03 — was obtained 10 centimorgans distal (telomeric) to the DNA marker D21S58. There was a significant probability (P<0.0001 ) of genetic-locus heterogeneity in the families. 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. (N Engl J Med 1991; 324:1381–4.)

AB - Background. Amyotrophic lateral sclerosis is a progressive neurologic disorder that commonly results in paralysis and death. Despite more than a century of research, no cause of, cure for, or means of preventing this disorder has been found. In a minority of cases, it is familial and inherited as an autosomal dominant trait with age-dependent penetrance. In contrast to the sporadic form of amyotrophic lateral sclerosis, the familial form provides the opportunity to use molecular genetic techniques to localize an inherited defect. Furthermore, such studies have the potential to discover the basic molecular defect causing motor-neuron degeneration. gene causing this disease to four DNA markers on the long arm of chromosome 21. Multipoint linkage analyses demonstrated linkage between the gene and these markers. The maximum lod score — 5.03 — was obtained 10 centimorgans distal (telomeric) to the DNA marker D21S58. There was a significant probability (P<0.0001 ) of genetic-locus heterogeneity in the families. 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. (N Engl J Med 1991; 324:1381–4.)

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U2 - 10.1056/NEJM199105163242001

DO - 10.1056/NEJM199105163242001

M3 - Article

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JO - New England Journal of Medicine

JF - New England Journal of Medicine

SN - 0028-4793

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