The genetics of amyotrophic lateral sclerosis

doi:10.1017/CBO9780511544873.052

51 - The genetics of amyotrophic lateral sclerosis

from Part IX - Motor neuron diseases

Published online by Cambridge University Press: 04 August 2010

Anthony E. Lang and

Ammar Al-Chalabi and

M. Flint Beal: Affiliation:
Cornell University, New York
Anthony E. Lang: Affiliation:
University of Toronto
Albert C. Ludolph: Affiliation:
Universität Ulm, Germany
Ammar Al-Chalabi: Affiliation:
Department of Neurology, Institute of Psychiatry, London, UK
Robert H. Brown: Affiliation:
Cecil B. Day Neuromuscular Laboratory, Massachusetts General Hospital East, Charlestown, MA, USA

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Summary

Models of inheritance

The genetics of a disease such as amyotrophic lateral sclerosis (ALS) require some flexibility in thinking about familiality compared with the genetics of isolated cases. About 10% of the time, an individual who develops ALS also has first-degree relatives who have been affected. For the remainder, the disease is said to be sporadic, but detailed investigation of the family tree may occasionally reveal that cousins or other more distant relatives have been affected. ALS can therefore be seen as a disease with an inheritance pattern that lies on a continuum from sporadic disease, to familial clustering to clear Mendelian familiality. For simplicity we have maintained the conventional separation of familial and sporadic disease, but as will become obvious, this distinction is largely artificial.

Familial ALS and the first descriptions

The concepts of genetics were coming into being at about the same time as the earliest descriptions of motor neuron diseases. Mendel presented his classic paper in 1865 (Mendel, 1865) in which he described his famous sweet pea hybridization experiments. He did not use the term gene or genetic to describe the heritable units but called them “formative elements.” Cambridge Professor of Biology William Bateson coined the term “genetics” (from the Greek “to generate”) in 1905 when applying for a university chair in a letter to the Cambridge zoologist, Adam Sedgwick. He wrote, “Such a word is badly wanted and if it were desirable to coin one, Genetics might do.”

Type: Chapter
Information: Neurodegenerative Diseases
Neurobiology, Pathogenesis and Therapeutics
, pp. 758 - 771

DOI: https://doi.org/10.1017/CBO9780511544873.052 [Opens in a new window]

Publisher: Cambridge University Press

Print publication year: 2005

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References

Abalkhail, H., Mitchell, J., Habgood, J., Orrell, R. & Belleroche, J. (2003). A new familial amyotrophic lateral sclerosis locus on chromosome 16q12.1–16q12.2. Am. J. Hum. Genet., 73, 383–9CrossRef Google Scholar PubMed

Ahmad-Annuar, A., Shah, P., Hafezparast, M.et al. (2003). No association with common Caucasian genotypes in exons 8, 13 and 14 of the human cytoplasmic dynein heavy chain gene (DNCHC1) and familial motor neuron disorders. Amyotroph. Lateral Scler. Other Motor Neuron Disord., 4, 150–7CrossRef Google Scholar PubMed

Al-Chalabi, A., Andersen, P. M., Chioza, B.et al. (1998). Recessive amyotrophic lateral sclerosis families with the D90A SOD1 mutation share a common founder: evidence for a linked protective factor. Hum. Mol. Genet., 7, 2045–50CrossRef Google Scholar

Al-Chalabi, A., Andersen, P. M., Nilsson, P.et al. (1999). Deletions of the heavy neurofilament subunit tail in amyotrophic lateral sclerosis. Hum. Mol. Genet., 8, 157–64CrossRef Google Scholar PubMed

Al-Chalabi, A., Enayat, Z. E., Bakker, M. C.et al. (1996). Association of apolipoprotein E epsilon 4 allele with bulbar-onset motor neuron disease. Lancet, 347, 159–60CrossRef Google Scholar PubMed

Al-Chalabi, A., Hansen, V. K., Simpson, C. L.et al. (2003a). Variants in the ALS2 gene are not associated with sporadic amyotrophic lateral sclerosis. NeurogeneticsCrossRef Google Scholar

Al-Chalabi, A., Scheffler, M. D., Smith, B. N.et al. (2003b). Ciliary neurotrophic factor genotype does not influence clinical phenotype in amyotrophic lateral sclerosis. Ann. Neurol., 54, 130–4CrossRef Google Scholar

Alexander, M. D., Traynor, B. J., Miller, N.et al. (2002). “True” sporadic ALS associated with a novel SOD-1 mutation. Ann. Neurol., 52, 680–3CrossRef Google Scholar PubMed

Andersen, P. M., Forsgren, L., Binzer, M.et al. (1996). Autosomal recessive adult-onset amyotrophic lateral sclerosis associated with homozygosity for Asp90Ala CuZn-superoxide dismutase mutation. A clinical and genealogical study of 36 patients. Brain, 119, 1153–72CrossRef Google Scholar PubMed

Andersen, P. M., Nilsson, P., Ala-Hurula, V.et al. (1995). Amyotrophic lateral sclerosis associated with homozygosity for an Asp90Ala mutation in CuZn-superoxide dismutase. Nat. Genet., 10, 61–6CrossRef Google Scholar PubMed

Andersen, P. M., Nilsson, P., Keranen, M. L.et al. (1997). Phenotypic heterogeneity in motor neuron disease patients with CuZn-superoxide dismutase mutations in Scandinavia. Brain, 10, 1723–37CrossRef Google Scholar

Andersen, P. M., Sims, K. B., Xin, W. W.et al. (2003). Sixteen novel mutations in the Cu/Zn superoxide dismutase gene in amyotrophic lateral sclerosis: a decade of discoveries, defects and disputes. Amyotroph. Lateral Scler. Other Motor Neuron Disord., 4, 62–73CrossRef Google Scholar PubMed

Bachus, R., Bader, S., Gessner, R. & Ludolph, A. C. (1997). Lack of association of apolipoprotein e epsilon 4 allele with bulbar-onset motor neuron disease. Ann. Neurol., 41, 417CrossRef Google Scholar PubMed

Bateson, W. (1906). Address. In Third Conference on Hybridisation, Cambridge, UK

Beckman, G. (1973). Population studies in northern Sweden. VI. Polymorphism of superoxide dismutase. Hereditas, 73, 305–10CrossRef Google Scholar PubMed

Ben Hamida, M., Hentati, F. & Ben Hamida, C. (1990). Hereditary motor system diseases (chronic juvenile amyotrophic lateral sclerosis). Conditions combining a bilateral pyramidal syndrome with limb and bulbar amyotrophy. Brain, 113, 347–63CrossRef Google Scholar PubMed

Chance, P. F., Rabin, B. A., Ryan, S. G.et al. (1998). Linkage of the gene for an autosomal dominant form of juvenile amyotrophic lateral sclerosis to chromosome 9q34. American Journal of Human Genetics, 62, 633–40CrossRef Google Scholar PubMed

Charcot, J. M. & Joffroy, A. (1869). Deux cas d'atrophie musculaire progressive avec lesions de la substance grise et des faisceaux antero-lateraux de la moelle epiniere. Arch. Physiol., Neurol. Pathol., 2, 744Google Scholar

Chen, Y. Z., Beunett, C. L., Huynh, H. M.et al. (2004). DNA/RNA helicase gene mutations in a form of juvenile amyotrophic lateral sclerosis (ALS4). Am. J. Hum. Genet., 74(6), 1128–35CrossRef Google Scholar

Corcia, P., Mayeux-Portas, V., Khoris, J.et al. (2002). Abnormal SMN1 gene copy number is a susceptibility factor for amyotrophic lateral sclerosis. Ann. Neurol., 51, 243–6CrossRef Google Scholar PubMed

Crow, J. F. (2000). The origins, patterns and implications of human spontaneous mutation. Nat. Rev. Genet., 1, 40–7CrossRef Google Scholar PubMed

Cudkowicz, M. E., McKenna-Yasek, D., Sapp, P. E.et al. (1997). Epidemiology of mutations in superoxide dismutase in amyotrophic lateral sclerosis [see comments]. Ann. Neurol., 41 (2), 210–21CrossRef Google Scholar

Devon, R., Helm, J., Rouleau, G.et al. (2003). The first nonsense mutation in alsin results in a homogeneous phenotype of infantile-onset ascending spastic paralysis with bulbar involvement in two siblings. Clin. Genet., 64, 210–15CrossRef Google Scholar

Dhaliwal, G. K. & Grewal, R. P. (2000). Mitochondrial DNA deletion mutation levels are elevated in ALS brains. NeuroReport, 11, 2507–2509CrossRef Google Scholar PubMed

Ding, H., Schwarz, D. S., Keene, A.et al. (2003). Selective silencing by RNAi of a dominant allele that causes amyotrophic lateral sclerosis. Aging Cell, 2, 209–17CrossRef Google Scholar PubMed

Drory, V. E., Birnbaum, M., Korczyn, A. D. & Chapman, J. (2001). Association of APOE varepsilon4 allele with survival in amyotrophic lateral sclerosis. J. Neurol. Sci., 190, 17–20CrossRef Google Scholar

Eymard-Pierre, E., Lesca, G., Dollet, S.et al. (2002). Infantile-onset ascending hereditary spastic paralysis is associated with mutations in the alsin gene. Am. J. Hum. Genet., 71, 518–27CrossRef Google Scholar PubMed

Figlewicz, D. A., Krizus, A., Martinoli, M. G.et al. (1994). Variants of the heavy neurofilament subunit are associated with the development of amyotrophic lateral sclerosis. Hum. Mol. Genet., 3, 1757–61CrossRef Google Scholar PubMed

Giess, R., Beck, M., Goetz, R., Nitsch, R. M., Toyka, K. V. & Sendtner, M. (2000). Potential role of LIF as a modifier gene in the pathogenesis of amyotrophic lateral sclerosis. Neurology, 54, 1003–5CrossRef Google Scholar PubMed

Giess, R., Braga, M., Holtmann, B., Tokya, K. & Sendtner, M. (2001). A CNTF null mutation as a potential modifier to disease onset in familial ALS with a mutation in the SOD-1 gene and transgenic SOD-1 mutant mice. J. Neurol., 248, 41–2Google Scholar

Giess, R., Goetz, R., Schrank, B., Ochs, G., Sendtner, M. & Toyka, K. (1998). Potential implications of a ciliary neurotrophic factor gene mutation in a German population of patients with motor neuron disease. Muscle Nerve, 21, 236–83.0.CO;2-#>CrossRef Google Scholar

Giess, R., Holtmann, B., Braga, M.et al. (2002). Early onset of severe familial amyotrophic lateral sclerosis with a SOD-1 mutation: potential impact of CNTF as a candidate modifier gene. Am. J. Hum. Genet., 70, 1277–86CrossRef Google Scholar PubMed

Graham, A. J., Macdonald, A. M. & Hawkes, C. H. (1997). British motor neuron disease twin study. [Review] [60 refs]. J. Neurol, Neurosurg. Psychiatr., 62, 562–9CrossRef Google Scholar

Hadano, S., Hand, C. K., Osuga, H.et al. (2001). A gene encoding a putative GTPase regulator is mutated in familial amyotrophic lateral sclerosis 2. Nat. Genet., 29, 166–73CrossRef Google Scholar PubMed

Hafezparast, M., Klocke, R., Ruhrberg, C.et al. (2003). Mutations in dynein link motor neuron degeneration to defects in retrograde transport. Science, 300, 808–12CrossRef Google Scholar PubMed

Hand, C. K., Mayeux-Portas, Y., Khoris, J.et al. (2001). Compound heterozygous D90A and D96N SOD1 mutations in a recessive amyotrophic lateral sclerosis family. Ann. Neurol., 49(2), 267–713.0.CO;2-D>CrossRef Google Scholar

Hand, C. K., Khoris, J., Salachas, F.et al. (2002). A novel locus for familial amyotrophic lateral sclerosis, on chromosome 18q. Am. J. Hum. Genet., 70, 251–6CrossRef Google Scholar PubMed

Hayward, C., Brock, D. J., Minns, R. A. & Swingler, R. J. (1998). Homozygosity for Asn86Ser mutation in the CuZn-superoxide dismutase gene produces a severe clinical phenotype in a juvenile onset case of familial amyotrophic lateral sclerosis [letter]. J. Med. Genet., 35, 174CrossRef Google Scholar

Hayward, C., Colville, S., Swingler, R. J. & Brock, D. J. (1999). Molecular genetic analysis of the APEX nuclease gene in amyotrophic lateral sclerosis. Neurology, 52, 1899–901CrossRef Google Scholar PubMed

Hentati, A., Bejaoui, K., Pericak Vance, M. A.et al. (1994). Linkage of recessive familial amyotrophic lateral sclerosis to chromosome 2q33–q35. Nat. Genet., 7, 425–8CrossRef Google Scholar PubMed

Hentati, A., Ouahchi, K., Pericak-Vance, M. A.et al. (1998). Linkage of a commoner form of recessive amyotrophic lateral sclerosis to chromosome 15q15–q22 markers [In Process Citation]. Neurogenetics., 2, 55–60CrossRef Google Scholar

Hosler, B. A., Siddique, T., Sapp, P. C.et al. (2000). Linkage of familial amyotrophic lateral sclerosis with frontotemporal dementia to chromosome 9q21–q22. J. Am. Med. Assoc., 284, 1664–9CrossRef Google Scholar PubMed

Imura, T., Shimohama, S., Kawamata, J. & Kimura, J. (1998). Genetic variation in the ciliary neurotrophic factor receptor alpha gene and familial amyotrophic lateral sclerosis [letter]. Annals of Neurology, 43, 275CrossRef Google Scholar

Jackson, M., Al-Chalabi, A., Enayat, Z. E., Chioza, B., Leigh, P. N. & Morrison, K. E. (1997). Copper/zinc superoxide dismutase 1 and sporadic amyotrophic lateral sclerosis: analysis of 155 cases and identification of a novel insertion mutation. Ann. Neurolog., 42, 803–7CrossRef Google Scholar PubMed

Jackson, M., Morrison, K. E., Al-Chalabi, A., Bakker, M. & Leigh, P. N. (1996). Analysis of chromosome 5q13 genes in amyotrophic lateral sclerosis: homozygous NAIP deletion in a sporadic case. Ann. Neurol., 39, 796–800CrossRef Google Scholar

Jones, C. T., Swingler, R. J. & Brock, D. J. (1994). Identification of a novel SOD1 mutation in an apparently sporadic amyotrophic lateral sclerosis patient and the detection of Ile113Thr in three others. Hum. Mol. Genet., 3(4), 649–50CrossRef Google Scholar

Kato, M., Aoki, M., Ohta, M.et al. (2001). Marked reduction of the Cu/Zn superoxide dismutase polypeptide in a case of familial amyotrophic lateral sclerosis with the homozygous mutation. Neurosci. Lett., 312, 165–8CrossRef Google Scholar

Kisby, G. E., Milne, J. & Sweatt, C. (1997). Evidence of reduced DNA repair in amyotrophic lateral sclerosis brain tissue. NeuroReport, 8, 1337–40CrossRef Google Scholar PubMed

Lacomblez, L., Doppler, V., Beucler, I.et al. (2002). APOE: a potential marker of disease progression in ALS. Neurology, 58, 1112–14CrossRef Google Scholar PubMed

Lambrechts, D., Storkebaum, E., Morimoto, M.et al. (2003). VEGF is a modifier of amyotrophic lateral sclerosis in mice and humans and protects motoneurons against ischemic death. Nat. Genet., 34, 383–94CrossRef Google Scholar PubMed

Lasker, G. W. (1968). The occurrence of identical (isonymous) surnames in various relationships in pedigrees: a preliminary analysis of the relation of surname combinations to inbreeding. Am. J. Hum. Genet., 20, 250–7Google Scholar PubMed

Lasker, G. W. (1977). A coefficient of relationship by isonymy: a method for estimating the genetic relationship between populations. Hum. Biol., 49, 489–93Google Scholar PubMed

Mawrin, C., Kirches, E. & Dietzmann, K. (2003). Single-cell analysis of mtDNA in amyotrophic lateral sclerosis: towards the characterization of individual neurons in neurodegenerative disorders. Pathol Res. Pract., 199, 415–18CrossRef Google Scholar PubMed

Maxwell, M. M., Pasinelli, P., Kazantsev, A. G. & Brown, R. H. Jr. (2004). RNA interference-mediated silencing of mutant superoxide dismutase rescues cyclosporin A-induced death in cultured neuroblastoma cells. Proc. Natl Acad. Sci. USA, 101, 3178–83CrossRef Google Scholar PubMed

Mendel, G. (1865). Versuche uber Pflanzen-Hybriden (Experiments in Plant Hybridization). In Verhandlungen es naturforschenden Vereines in Brunn 4 (Natural History Society of Brunn 4) Bohemia, Czechoslovakia

Moreira, M. C., Klur, S., Watanabe, M.et al. (2004). Senataxin, the orthologue of a yeast RNA helicase, is mutant in ataxia-ocular apraxia 2. Nat. Genet., 36, 225–7CrossRef Google Scholar

Morton, N. E. (1955). Sequential tests for the detection of linkage. Am. J. Hum. Genet., 7, 277–318Google Scholar PubMed

Moulard, B., Salachas, F., Chassande, B.et al. (1998). Association between centromeric deletions of the SMN gene and sporadic adult-onset lower motor neuron disease. Ann. Neurol., 43, 640–4CrossRef Google Scholar PubMed

Moulard, B., Sefiani, A., Laamri, A., Malafosse, A. & Camu, W. (1996). Apolipoprotein E genotyping in sporadic amyotrophic lateral sclerosis, evidence for a major influence on the clinical presentation and prognosis. J. Neurol. Sci., 139, 34–7CrossRef Google Scholar

Mui, S., Rebeck, G. W., McKenna Yasek, D., Hyman, B. T. & Brown, R. H. Jr. (1995). Apolipoprotein E epsilon 4 allele is not associated with earlier age at onset in amyotrophic lateral sclerosis. Ann. Neurol., 38, 460–3CrossRef Google Scholar

Niemann, S., Joos, H., Meyer, T.et al. (2004). Familial ALS in Germany: origin of the R115G SOD1 mutation by a founder effect. J. Neurol. Neurosurg. Psychiatr., 75, 1186–8CrossRef Google Scholar PubMed

Nishimura, A. L., Mitne-Neto, M., Silva, H. C., Oliveira, J. R., Vainzof, M. & Zatz, M. (2004a). A novel locus for late onset amyotrophic lateral sclerosis/motor neurone disease variant at 20q13. J. med. Genet., 41, 315–20CrossRef Google Scholar

Nishimura, A. L., Mitne-Neto, M., Silva, H. C.et al. (2004b). A mutation in the vesicle-trafficking protein VAPB causes late-onset spinal muscular atrophy and amyotrophic lateral sclerosis. Am. J. Hum. Genet., 75 822–31CrossRef Google Scholar

Olkowski, Z. L. (1998). Mutant AP endonuclease in patients with amyotrophic lateral sclerosis. NeuroReport, 9, 239–42CrossRef Google Scholar PubMed

Orrell, R. W., Habgood, J. J., Belleroche, J. S. & Lane, R. J. M. (1997). The relationship of spinal muscular atrophy to motor neuron disease: Investigation of SMN and NAIP gene deletions in sporadic and familial ALS. J. Neurol. Sci., 145, 55–61CrossRef Google Scholar PubMed

Orrell, R. W., King, A. W., Lane, R. J. & Belleroche, J. S. (1995). Investigation of a null mutation of the CNTF gene in familial amyotrophic lateral sclerosis. J. Neurol. Sci., 132, 126–8CrossRef Google Scholar PubMed

Parboosingh, J. S., Meininger, V., McKenna-Yasek, D., Brown, R. H. Jr. & Rouleau, G. A. (1999). Deletions causing spinal muscular atrophy do not predispose to amyotrophic lateral sclerosis. Archives of Neurology, 56, 710–12CrossRef Google Scholar

Parboosingh, J. S., Rouleau, G. A., Meninger, V., McKenna Yasek, D., Brown, R. H. Jr. & Figlewicz, D. A. (1995). Absence of mutations in the Mn superoxide dismutase or catalase genes in familial amyotrophic lateral sclerosis. Neuromuscul. Disord., 5, 7–10CrossRef Google Scholar PubMed

Parekh-Olmedo, H., Krainc, D. & Kmiec, E. B. (2002). Targeted gene repair and its application to neurodegenerative disorders. Neuron, 33, 495–8CrossRef Google Scholar PubMed

Parton, M. J., Broom, W., Andersen, P. M.et al. (2002). D90A-SOD1 mediated amyotrophic lateral sclerosis: a single founder for all cases with evidence for a Cis-acting disease modifier in the recessive haplotype. Hum. Mutat., 20, 473CrossRef Google Scholar PubMed

Puls, I., Jonnakuty, C., LaMonte, B. H.et al. (2003). Mutant dynactin in motor neuron disease. Nat. Genet., 33, 455–6CrossRef Google Scholar PubMed

Radunovic, A. & Leigh, P. N. (1996). Cu/Zn superoxide dismutase gene mutations in amyotrophic lateral sclerosis: Correlation between genotype and clinical features. J. Neurol. Neurosurg. Psychiatr., 61, 565–72CrossRef Google Scholar PubMed

Rezania, K., Yan, J., Dellefave, L.et al. (2003). A rare Cu/Zn superoxide dismutase mutation causing familial amyotrophic lateral sclerosis with variable age of onset, incomplete penetrance and a sensory neuropathy. Amyotroph. Lateral Scler. Other Motor Neuron Disord., 4, 162–6CrossRef Google Scholar

Ro, L. S., Lai, S. L., Chen, C. M. & Chen, S. T. (2003). Deleted 4977-bp mitochondrial DNA mutation is associated with sporadic amyotrophic lateral sclerosis: a hospital-based case-control study. Muscle Nerve, 28, 737–43CrossRef Google Scholar PubMed

Rooke, K., Figlewicz, D. A., Han, F. Y. & Rouleau, G. A. (1996). Analysis of the KSP repeat of the neurofilament heavy subunit in familial amyotrophic lateral sclerosis. Neurology, 46, 789–90CrossRef Google Scholar

Rosen, D. R. (2004). A shared chromosome-21 haplotype among amyotrophic lateral sclerosis families with the A4V SOD1 mutation. Clin. Genet., 66, 247–50CrossRef Google Scholar PubMed

Rosen, D. R., Siddique, T., Patterson, D.et al. (1993). Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis [published erratum appears in Nature 1993 Jul 22;364(6435):362] [see comments]. Nature, 362, 59–62CrossRef Google Scholar

Rosso, S. M. & Swieten, J. C. (2002). New developments in frontotemporal dementia and parkinsonism linked to chromosome 17. Curr. Opin. Neurol., 15, 423–8CrossRef Google Scholar PubMed

Ruddy, D. M., Parton, M. J., Al-Chalabi, A.et al. (2003). Two families with familial amyotrophic lateral sclerosis are linked to a novel locus on chromosome 16q. Am. J. Hum. Genet., 73, 390–6CrossRef Google Scholar PubMed

Sapp, P. C., Hosler, B. A., McKenna-Yasek, D.et al. (2003). Identification of two novel loci for dominantly inherited familial amyotrophic lateral sclerosis. Am. J. Hum. Genet., 73, 397–403CrossRef Google Scholar PubMed

Siddique, T., Figlewicz, D. A., Pericak Vance, M. A.et al. (1991). Linkage of a gene causing familial amyotrophic lateral sclerosis to chromosome 21 and evidence of genetic-locus heterogeneity [published errata appear in N Engl J Med 1991 Jul 4;325(1):71 and 1991 Aug 15;325(7):524] [see comments]. N. Engl. J. Med., 324, 1381–4CrossRef Google Scholar

Siddique, T., Hong, S., Brooks, B.et al. (1998a). X-linked dominant locus for late-onset familial amyotrophic lateral sclerosis. Am. J. Hum. Genet.Google Scholar

Siddique, T., Pericak-Vance, M. A., Caliendo, J.et al. (1998b). Lack of association between apolipoprotein E genotype and sporadic amyotrophic lateral sclerosis. Neurogenetics, 1, 213–16CrossRef Google Scholar

Takahashi, R. (1995). Deficiency of human ciliary neurotrophic factor (CNTF) is not causally related to amyotrophic lateral sclerosis (ALS). Clin. Neurol., 35, 1543–5Google Scholar

Takahashi, R., Yokoji, H., Misawa, H., Hayashi, M., Hu, J. & Deguchi, T. (1994). A null mutation in the human CNTF gene is not causally related to neurological diseases. Nat. Genet., 7, 79–84CrossRef Google Scholar

Tandan, R., Robison, S. H., Munzer, J. S. & Bradley, W. G. (1987). Deficient DNA repair in amyotrophic lateral sclerosis cells. J. Neurol. Sci., 79, 189–203CrossRef Google Scholar PubMed

Tomblyn, M., Kasarskis, E. J., Xu, Y. & St Clair, D. K. (1998). Distribution of MnSOD polymorphisms in sporadic ALS patients. J. Mol. Neurosci., 10, 65–6CrossRef Google Scholar PubMed

Tomkins, J., Banner, S. J., McDermott, C. J. & Shaw, P. J. (2001). Mutation screening of manganese superoxide dismutase in amyotrophic lateral sclerosis. NeuroReport, 12, 2319–22CrossRef Google Scholar PubMed

Tomkins, J., Dempster, S., Banner, S. J., Cookson, M. R. & Shaw, P. J. (2000). Screening of AP endonuclease as a candidate gene for amyotrophic lateral sclerosis (ALS). NeuroReport, 11, 1695–7CrossRef Google Scholar

Tomkins, J., Usher, P., Slade, J. Y.et al. (1998). Novel insertion in the KSP region of the neurofilament heavy gene in amyotrophic lateral sclerosis (ALS). NeuroReport, 9, 3967–70CrossRef Google Scholar

Landeghem, G. F., Tabatabaie, P., Beckman, G., Beckman, L. & Andersen, P. M. (1999). Manganese-containing superoxide dismutase signal sequence polymorphism associated with sporadic motor neuron disease. Eur. J. Neurol., 6, 639–44CrossRef Google Scholar PubMed

Veldink, J. H., Berg, L. H., Cobben, J. M.et al. (2001). Homozygous deletion of the survival motor neuron 2 gene is a prognostic factor in sporadic ALS. Neurology, 56, 749–52CrossRef Google Scholar PubMed

Xiang, Y., Cole-Strauss, A., Yoon, K., Gryn, J. & Kmiec, E. B. (1997). Targeted gene conversion in a mammalian CD34+-enriched cell population using a chimeric RNA/DNA oligonucleotide. J. Mol. Med., 75, 829–35CrossRef Google Scholar

Yang, Y., Hentati, A., Deng, H. X.et al. (2001). The gene encoding alsin, a protein with three guanine-nucleotide exchange factor domains, is mutated in a form of recessive amyotrophic lateral sclerosis. Nat. Genet., 29, 160–5CrossRef Google Scholar