Linkage disequilibrium detected between dystrophia myotonica and APOC2 locus in the Finnish population

Abstract

Three polymorphic loci APOC2, CKMM and p134C were used to haplotype 15 Finnish dystrophia myotonica (DM) families representing about one third of all DM patients in this isolated population. Compound APOC2 and CKMM haplotypes reveal linkage disequilibrium: 90% of DM chromosomes co-occur with the haplotypes that occur in 31% of normal chromosomes only. The same disequilibrium is present when only polymorphisms occurring at the APOC2 locus are used. Surprisingly, no statistically significant linkage disequilibrium was discovered at the CKMM locus alone. Of the meiotic events, 84% were informative when both APO2 and CKMM loci were used. When studied selectively, 60% of meiotic events were informative at the APOC2 locus, whereas CKMM alone resulted in 65% meiotic informativeness. The distal marker p134C was found to have an unfortunately low information content in our population.

3? creatine kinase (M-type) polymorphisms linked to myotonic dystrophy in Italian and Spanish populations

“…Our analysis confirms tight linkage of CKMM to DM as previously shown in other populations (Brunner et al 1989: Nokelainen et al 1990Yamaoka et al 1990). Present data also support evidence of DM genetic homogeneity in different ethnic groups (Takemoto et al 1990) and are relevant for counselling and prenatal diagnsosis of this disease in south European populations.…”

“…Haplotypes were assigned by hand according to segregation analysis. Allelic associations and linkage disequilibrium quantification were evaluated essentially according to Nokelainen et al (1990). Two-point linkage analysis was performed using the MLINK program [Version 5.03, updated by Ott (1985)] assuming a gene frequency of 1/10000 for the mutant DM allele.…”

“…Linkage studies and informativity of C K M M in D M families from North America, Canada, The Netherlands and Finland have been reported. They provide suitable information for D M diagnostic programs (Brunner et al 1989;Nokelainen et al 1990; Y a m a o k a et al. 1990).…”

Report of the committee on the genetic constitution of chromosome 19

“…"south" of D19S63. Linkage disequilibrium between DM and several proximal marker loci in the Finnish and the Franco-Canadian population (Korneluk and de Jong, 1991;Nokelainen et al, 1990;Morissette et al, 1991) has been explained as resulting from founder effects Thibault et al, 1991). Unexpectedly, however, strong linkage disequilibria have also been observed with probe pDIO (D19S63; (Harley et al, 1991b)) in the British and, subsequently, with the D19S112 marker in the Dutch population (Smeets, 1991) but not with markers outside the ERCC1-D19S51 interval.…”

The DM mutation; diagnostic applications in the Finnish population

“…The presence of linkage disequilibrium between the marker haplotypes and the disease phenotype could further strengthen the diagnostic reliability of this method in a given population. Moreover, such linkage disequilibrium had been demonstrated in the French-Canadian population (Laberge 1989, in the Finnish population (Nokelainen et al 1990) and in an outbred European population , Cob0 et al 1992, making diagnostic application of these polymorphisms relevant.…”