Haplotype analysis of the DM1 locus in the Serbian population.
OBJECTIVE
Analysis of the CTG-repeat number and three biallelic markers, Alu(+/-), HinfI(+/-), and TaqI(+/-), in the DMPK gene in healthy and myotonic dystrophy type 1 (DM1) Serbian individuals. Also, the consideration of haplotypes in the light of the proposed models of CTG-repeat evolution and origin of the DM1 mutation.


METHODS
Markers were analyzed by PCR and haplotypes were obtained on 203 unrelated normal chromosomes and 24 unrelated DM1 chromosomes.


RESULTS
A strong linkage disequilibrium was detected between the three biallelic markers alone (P <0.0001) and between distinct CTG-repeat size classes and reconstructed haplotypes. Greater than 98% of normal chromosomes contain (+++) and (- - -) haplotypes. The (+++) haplotype is the most common, while the (CTG)(9-17) are the most frequent alleles. We found a complete association of (+++) haplotype with (CTG)(> or =18) and mutated alleles.


CONCLUSIONS
(CTG)(9-17)/(+++) haplotype is the ancestral haplotype and DM1 mutation occurred on (CTG)(18-35)/+++ chromosome.
Krndija
D
D
Faculty of Biology, University of Belgrade, Belgrade, Serbia and Montenegro.
Savić
D
D
Mladenović
J
J
Rakocević-Stojanović
V
V
Apostolski
S
S
Todorović
S
S
Romac
S
S
D016022:Case-Control Studies; D005260:Female; D005819:Genetic Markers; D006239:Haplotypes; D006801:Humans; D008297:Male; D009223:Myotonic Dystrophy / Q000235:genetics*; D065636:Myotonin-Protein Kinase; D010375:Pedigree; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D018911:Trinucleotide Repeats; D015022:Yugoslavia
C585517:DMPK protein, human; D005819:Genetic Markers; D065636:Myotonin-Protein Kinase; D017346:Protein Serine-Threonine Kinases