Convergent myotonic dystrophy (DM) haplotypes on 19q13.3: Potential inconsistencies in human disease gene localization

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

OSTI ID:134132

Tsilfidis, C ^[1]; Whiting, E J ^[2]; Korneluk, R G ^[2]

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1. Eye Research Institute of Canada, Toronto (Canada)
2. Univ. of Ottawa (Canada)

Myotonic dystrophy (DM) is an autosomal dominant neuromuscular disease which has been shown to be caused by an unstable trinucleotide repeat located on chromosome 19q. We have conducted extensive haplotype analysis on 103 DM chromosome using thirteen 19q13.3 loci identifying 18 RFLPs, spanning a physical distance of 1.3 Mb containing the myotonic dystrophy gene. Three major haplotypes, H1, H2 and H3, comprising 45.6% of the DM chromosomes, were observed in our population. The later two haplotypes, observed exclusively on DM chromosomes of French Canadian origin, contain a 500 kb core region that is identical. The low frequency of this core on normal chromosomes (0.8%) is consistent with a mapping of the DM gene within this region. However, the DM mutation is found 160 kb distal to the point of divergence between these two haplotypes. In contrast, the 450 kb shared by haplotypes H1 and H2 contain the DM mutation. Further, analysis of the DM region using a polymorphic microsatellite GJ-VSSM2 located 15 kb telomeric to the DM gene revealed strong allelic association of allele V on DM chromosomes (present on 6% of normal and 88.2% of DM chromosomes). The fact that allele V was found on all DM chromosomes with the three major haplotypes is indicative of their common origin and includes the two French Canadian haplotypes which share a region proximal to the DM mutation. This analysis indicates that convergent haplotypes, in the absence of a more extensive linkage disequilibrium analysis, may lead to a spurious disease gene localization.

• OSTI ID: 134132
• 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
GENE MUTATIONS
GENES
GENETIC MAPPING
GENETICS
HEREDITARY DISEASES
HUMAN CHROMOSOME 19
INSTABILITY
MUSCLES
MUTATION FREQUENCY
NERVOUS SYSTEM DISEASES
NUCLEOTIDES
PATIENTS
RFLPS
STATISTICS