A novel locus for familial amyotrophic lateral sclerosis, on chromosome 18q - PubMed (original) (raw)

A novel locus for familial amyotrophic lateral sclerosis, on chromosome 18q

Collette K Hand et al. Am J Hum Genet. 2002 Jan.

Erratum in

Abstract

Amyotrophic lateral sclerosis (ALS) is an adult-onset degenerative disorder characterized by the death of motor neurons in the cortex, brain stem, and spinal cord. Despite intensive research the basic pathophysiology of ALS remains unclear. Although most cases are sporadic, approximately 10% of ALS cases are familial (FALS). Mutations in the Cu/Zn superoxide dismutase (SOD1) gene cause approximately 20% of FALS. The gene(s) responsible for the remaining 80% of FALS remain to be found. Using a large European kindred without SOD1 mutation and with classic autosomal dominant adult-onset ALS, we have identified a novel locus by performing a genome scan and linkage analysis. The maximum LOD score is 4.5 at recombination fraction 0.0, for polymorphism D18S39. Haplotype analysis has identified a 7.5-cM, 8-Mb region of chromosome 18q21, flanked by markers D18S846 and D18S1109, as a novel FALS locus.

PubMed Disclaimer

Figures

Figure 1

Figure 1

Informative section of pedigree Fr017. Individuals available for typing are indicated by the generated genotype data. The markers examined are shown. Alleles in parentheses are inferred. All inferred haplotypes were reconstructed on the basis of minimal recombinations. A solid black bar indicates the disease haplotype. A thin black line denotes an unknown or unphased haplotype. Key recombinants (IV:37 and IV:67) are indicated by an asterisk (*). Alleles given refer to the Fondation Jean Dausset CEPH alleles, when available. Information is shown only for relevant individuals. To preserve confidentiality, the sex of all individuals has been disguised; in addition, six unaffected haplotype carriers have been omitted from the pedigree.

References

Electronic-Database Information

    1. Center for Medical Genetics, Marshfield Medical Research Foundation, http://research.marshfieldclinic.org/genetics/ (for genetic maps)
    1. Cooperative Human Linkage Center, The, http://lpg.nci.nih.gov/CHLC/
    1. Fondation Jean Dausset CEPH, www.cephb.fr
    1. GenBank Overview, http://www.ncbi.nlm.nih.gov/Genbank/GenbankOverview.html (for TXNL gene [accession number NM_004786])
    1. Genome Database, The, http://www.gdb.org

References

    1. Al Chalabi A, Leigh PN (2000) Recent advances in amyotrophic lateral sclerosis. Curr Opin Neurol 13:397–405 - PubMed
    1. Anderson MA, Gusella JF (1984) Use of cyclosporin A in establishing Epstein-Barr virus-transformed human lymphoblastoid cell lines. In Vitro 20:856–858 - PubMed
    1. Andreassen OA, Ferrante R, Klivenyi P, Klein AM, Shinobu LA, Epstin CJ, Beal MF (2000) Partial deficiency of manganese superoxide dismutase exacerbates a transgenic mouse model of amyotrophic lateral sclerosis. Ann Neurol 47:447–455 - PubMed
    1. Bedlack RS, Strittmatter WJ, Morgenlander JC (2000) Apolipoprotein E and neuromuscular disease: a critical review of the literature. Arch Neurol 57:1561–1565 - PubMed
    1. Boukaftane Y, Khoris J, Moulard B, Salachas F, Meininger V, Malafosse A, Camu W, Rouleau GA (1998) Identification of six novel SOD1 gene mutations in familial amyotrophic lateral sclerosis. Can J Neurol Sci 25:192–196 - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources