A linkage study of Machado-Joseph disease - refining the localisation of the gene

Journal Article · Thu Sep 01 04:00:00 EDT 1994 · American Journal of Human Genetics

OSTI ID:134692

Gaspar, C; Twist, E C; Maciel, P ^[1]

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1. McGill Univ., Quebec (Canada); and others

Machado-Joseph disease (MJD) is an autosomal dominant neurodegenerative ataxia originally described in families of Azorean-Portuguese descent. It is believed to be due to the mutation of a single, as yet unidentified gene which has been mapped using genetic linkage analysis to a 29 cM region of chromosome 14q24.3-q32 in five Japanese families. The aim of this study was to refine the localization of the MJD gene by typing additional markers in this 29 cM interval. Blood was collected and DNA isolated from 355 individuals including 171 affected persons who are part of 6 Portuguese/Azorean, 6 American/Azorean and 1 Brazilian kindred. Pedigrees were typed with highly polymorphic di- and tetranucleotide repeat markers spanning the 29 cM region of chromosome 14q containing the gene. Markers tested include D14S74, D14S55, D14S124, D14S48, D14S128, D14S68, D14S256, AFM343vfl, D14S45, and D14S51. Linkage between the MJD locus and the markers was analyzed using the computer programs LIPED and LINKAGE. In addition, haplotype analysis of all 13 families was carried out. To date, the maximum cumulative two point lod score of 14.34 at a recombination fraction of 0.05 has been obtained with the marker AFM343vfl. From haplotype analysis, D14S68 and AFM343vfl have been identified as flanking markers. Thus the region of chromosome 14q containing the MJD gene has been narrowed from an interval of 29 cm to approximately 11 cM.

• OSTI ID: 134692
• Report Number(s): CONF-941009--
• Journal Information: American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: Suppl.3 Vol. 55; ISSN AJHGAG; ISSN 0002-9297
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
BIOLOGICAL MARKERS
DOMINANT MUTATIONS
GENES
GENETIC MAPPING
GENETICS
HEREDITARY DISEASES
HUMAN CHROMOSOME 14
L CODES
NERVOUS SYSTEM DISEASES
NUCLEOTIDES
PATIENTS
RESOLUTION
STATISTICS