title: Use of variable simple sequence motifs as genetic markers: application to study of myotonic dystrophy.
abstract: Among the many classes of repetitive elements present in the human genome, the ubiquitous "simple sequence motifs" (SSMs) composed of [A]n, [TG]n, [AG]n or codon-tandem repeats form a major source of genetic variation. Here we report a detailed molecular-genetic study of a "variable simple sequence motif" (VSSM) in the apolipoprotein C2 (apoC2) gene, which maps to the 19q13.2 region in the vicinity of the myotonic dystrophy (DM) locus. By combining in vitro DNA-amplification using the polymerase chain reaction and high-resolution gel electrophoresis, we could demonstrate a high degree of allelic variation with at least ten alleles, which differ in the number of repeated [TG] or [AG] dinucleotide units. Similar results were found for the somatostatin I gene locus. To evaluate the usefulness of SSM-length polymorphisms as genetic markers, the apoC2-VSSM was employed for linkage analysis in DM families. Our results establish that the orientation of the apolipoprotein gene cluster on 19q is cenapoE-apoC2-ter and indicate that the many thousands of structurally similar VSSMs in the human genome represent a rich source of highly informative genetic and diagnostic markers.
authors.affiliation: Department of Human Genetics, Radboud Hospital, University Nijmegen, The Netherlands.
authors.forename: H J
authors.initials: HJ
authors.lastname: Smeets
authors.forename: H G
authors.initials: HG
authors.lastname: Brunner
authors.forename: H H
authors.initials: HH
authors.lastname: Ropers
authors.forename: B
authors.initials: B
authors.lastname: Wieringa
mesh_terms: D053304:Apolipoprotein C-II; D001056:Apolipoproteins C / Q000235:genetics; D002888:Chromosomes, Human, Pair 19; D005260:Female; D005819:Genetic Markers; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D005810:Multigene Family; D009223:Myotonic Dystrophy / Q000235:genetics*; D015345:Oligonucleotide Probes; D010375:Pedigree; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D012091:Repetitive Sequences, Nucleic Acid
chemical_list: D053304:Apolipoprotein C-II; D001056:Apolipoproteins C; D005819:Genetic Markers; D015345:Oligonucleotide Probes