塞尔维亚人群中DM1基因座的单倍型分析。

Haplotype analysis of the DM1 locus in the Serbian population.

作者信息

Krndija D, Savić D, Mladenović J, Rakocević-Stojanović V, Apostolski S, Todorović S, Romac S

机构信息

Faculty of Biology, University of Belgrade, Belgrade, Serbia and Montenegro.

出版信息

Acta Neurol Scand. 2005 Apr;111(4):274-7. doi: 10.1111/j.1600-0404.2005.00402.x.

DOI:10.1111/j.1600-0404.2005.00402.x

PMID:15740580

Abstract

OBJECTIVES

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.

MATERIALS AND 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.

摘要

目的

分析健康塞尔维亚人和1型强直性肌营养不良症（DM1）患者的DMPK基因中的CTG重复序列数量以及三个双等位基因标记Alu(+/-)、HinfI(+/-)和TaqI(+/-)。同时，根据提出的CTG重复序列进化模型和DM1突变起源来考虑单倍型。

材料与方法

通过聚合酶链反应（PCR）分析标记，并在203条无关的正常染色体和24条无关的DM1染色体上获得单倍型。

结果

单独的三个双等位基因标记之间（P <0.0001）以及不同的CTG重复序列大小类别与重建的单倍型之间检测到强烈的连锁不平衡。超过98%的正常染色体包含（+++）和（---）单倍型。（+++）单倍型最为常见，而（CTG）(9 - 17)是最常见的等位基因。我们发现（+++）单倍型与（CTG）（≥18）及突变等位基因完全相关。