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CTG Expansion & Haplotype Analysis in DM1 Gene in Healthy Iranian Population

Published online by Cambridge University Press:  02 December 2014

Bahareh Shojasaffar ,
Neda Moradin ,
Kimia Kahrizi ,
Ana Maria Cobo  and
Hossein Najmabadi
Bahareh Shojasaffar
Affiliation:
Genetics Research Center, University of Social Welfare & Rehabilitation Sciences, Tehran, Iran
Neda Moradin
Affiliation:
Genetics Research Center, University of Social Welfare & Rehabilitation Sciences, Tehran, Iran
Kimia Kahrizi
Affiliation:
Genetics Research Center, University of Social Welfare & Rehabilitation Sciences, Tehran, Iran
Ana Maria Cobo
Affiliation:
Molecular Diagnostic Unit, Hospital Donostia, San Sebastian, Spain
Hossein Najmabadi
Affiliation:
Genetics Research Center, University of Social Welfare & Rehabilitation Sciences, Tehran, Iran
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Abstract

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Myotonic dystrophy type 1 (DM1) is due to an unstable expansion of CTG repeat in the DMPK gene (19q13.3). The CTG repeat is highly polymorphic (5 to 37) in healthy individuals. According to the hypothesis that expanded (CTG)n alleles originated from larger normal alleles, there may exist a correlation between the prevalence of DM1 and the frequency of large size normal alleles. Strong linkage disequilibrium between different length alleles and the three biallelic markers, Alu, Hinf1 and Taq1, has been reported.

Objective:

To determine the distribution of normal alleles, the frequency of larger normal alleles and analysis of the three biallelic markers, in healthy Iranian controls.

Material and Methods:

Polymerase chain reaction (PCR) was conducted on two hundred unrelated healthy individuals from different ethnic groups living in Iran to determine the size of the alleles. Markers were analyzed by PCR/RFLP on 174 chromosomes from other control healthy individuals.

Results:

Our data reveals that 23.7% of alleles had 5 CTG repeats and 7.2% of alleles had >18 CTG repeats. The analysis of haplotypes revealed that 75% of CTG5 and 80% of CTG>18 had the (+++) haplotype.

Conclusion:

The frequency of alleles with CTG>18 in Iran is similar to that of Western Europe and Japan.

Résumé:

<span class='bold'>RÉSUMÉ:</span>

La dystrophie myotonique de type 1 (DM1) est due à une expansion instable d’une répétition CTG dans le gène DMPK (19q13.3). La répétition CTG est très polymorphe (de 5 à 37 répétitions) chez les sujets sains. En se basant sur l’hypothèse selon laquelle les allèles porteurs d’une expansion (CTG)n proviennent d’allèles normaux de grande taille, il pourrait exister une corrélation entre la prévalence de la DM1 et la fréquence des allèles normaux de grande taille. Un déséquilibre de liaison marqué entre des allèles de différentes tailles et trois marqueurs bisalléliques, Alu, Hinfl et Taq1 a été rapporté.

<span class='bold'><span class='italic'>Objectif:</span></span>

Le but de l’étude était de déterminer la distribution des allèles normaux ainsi que la fréquence des allèles normaux de grande taille et d’analyser ces trois marqueurs bisalléliques chez des sujets témoins iraniens en santé.

<span class='bold'><span class='italic'>Matériels et méthodes:</span></span>

La taille des allèles a été déterminée par réaction en chaîne de la polymérase (PCR) chez deux cents sujets iraniens en santé, non apparentés, appartenant à différents groupes ethniques vivant en Iran. Cent soixantequatorze chromosomes provenant de sujets témoins en santé ont été analysés par PCR/RFLP pour identifier les marqueurs.

<span class='bold'><span class='italic'>Résultats:</span></span>

Selon nos données, 23,7% des allèles avaient 5 répétitions CTG et 7,2% des allèles avaient plus de 18 répétitions. L’analyse d’haplotype a montré que 75% des allèles porteurs de 5 CTG et 80% des allèles porteurs de plus de 18 CTG étaient également porteurs de l’haplotype (+++). Conclusion : La fréquence des allèles porteurs de plus de 18 CTG est semblable à celle qu’on retrouve en Europe de l’Ouest et au Japon.

Type
Original Articles
Information
Canadian Journal of Neurological Sciences , Volume 35 , Issue 2 , May 2008 , pp. 216 - 219
Copyright
Copyright © The Canadian Journal of Neurological 2008

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