Abstract
Myotonic dystrophy type 1 (DM1) is an autosomal dominant neuromuscular disorder caused by a CTG trinucleotide expansion at the DM1 locus. In this study, we investigated the frequency distribution of various CTG repeats in normal alleles and haplotyped the normal and expanded DM1 locus in a group of Taiwanese people. In the 496 normal chromosomes examined, up to 18 alleles with different CTG lengths from 5 to 30 repeats were found and the frequency of (CTG)>18 alleles was only 1.4% (7/496), predicting a low prevalence of DM1. In addition, there is no absolute association between (CTG)5–19 alleles and Alu insertion/deletion polymorphism observed on normal chromosomes. All DM1 alleles examined, however, were found to be associated with the Alu insertion. Further detailed genetic analysis demonstrated that at least eight haplotypes, including a new haplotype (L), were present in the Taiwanese population and that all DM1 alleles were with the same haplotype (haplotype A) as that identified in Canadian and Japanese DM1 populations. These findings support the notion that the out-of-Africa DM1 alleles were originated by stepwise expansion from a pool of large-sized normal chromosomes with haplotype A.
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Acknowledgements
We are grateful to the normal and DM1 volunteers for their cooperation; Dr. Chuan Li for the valuable comments. This work was supported by grants from the National Science Council of the Republic of China (NSC 89-2320-B040-068 and NSC89-2320-B-040-063), the Chung Shan Medical and Dental College Research Fund CSMC-89-OM-A-075.
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Pan, H., Lin, HM., Ku, WY. et al. Haplotype analysis of the myotonic dystrophy type 1 (DM1) locus in Taiwan: implications for low prevalence and founder mutations of Taiwanese myotonic dystrophy type 1. Eur J Hum Genet 9, 638–641 (2001). https://doi.org/10.1038/sj.ejhg.5200684
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DOI: https://doi.org/10.1038/sj.ejhg.5200684
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