Tight linkage between myotonic dystrophy and apolipoprotein E genes revealed with allele-specific oligonucleotides.
In 16 families with myotonic dystrophy (DM) a novel approach based on use of allele-specific oligonucleotides has been employed to study the linkage relationship between the apolipoprotein E (APOE) gene and DM. Synthetic oligonucleotides, designed to discriminate between APOE alleles epsilon 3 and epsilon 4, enabled us to distinguish heterozygous carriers in a hybridization assay. In a subset of families, the relevant segment of the APOE gene was enzymatically amplified to increase the sensitivity of the method. For DM and APOE, a maximum lod score (zmax of 7.47 was obtained at a recombination frequency (theta) of 0.047 (male theta = female theta). No recombination (maximum lod score of 5.61 at theta = 0.0) was found between APOE and the apolipoprotein CII (APOC2) gene. These results suggest that, in addition to APOC2, APOE is a useful marker for presymptomatic DM diagnosis.
Smeets
B
B
Department of Human Genetics, Radboud Hospital, University of Nijmegen, The Netherlands.
Poddighe
J
J
Brunner
H
H
Ropers
H H
HH
Wieringa
B
B
D000483:Alleles; D000595:Amino Acid Sequence; D001057:Apolipoproteins E / Q000235:genetics*; D001483:Base Sequence; D004247:DNA / Q000097:blood / Q000235:genetics; D005784:Gene Amplification; D005796:Genes; D008040:Genetic Linkage; D006801:Humans; D008969:Molecular Sequence Data; D009223:Myotonic Dystrophy / Q000097:blood / Q000235:genetics*; D009693:Nucleic Acid Hybridization; D009838:Oligodeoxyribonucleotides; D011110:Polymorphism, Genetic
D001057:Apolipoproteins E; D009838:Oligodeoxyribonucleotides; D004247:DNA