PMID: 11929851Apr 4, 2002Paper

Age and insertion site dependence of repeat number instability of a human DM1 transgene in individual mouse sperm

Human Molecular Genetics
Yun ZhangM L Meistrich

Abstract

Precise measurement of germline repeat number mutations is important for understanding the molecular etiology of expanded trinucleotide repeat diseases. We used single genome-equivalent PCR of sperm DNA to measure the mutation frequencies in two lines of Dmt transgenic mice containing an expanded CTG.CAG tract on an identical genetic background. Single genome-equivalent PCR indicated that apparent mutational spectra derived in other investigations from PCR of bulk sperm DNA were largely the consequence of PCR stutter and not mutations. Here we show that sperm from 8-week-old Dmt-D mice had a significantly higher mutation frequency (change of >1 repeat) (14.2%) than those of Dmt-E mice of the same age (5.5%), in agreement with pedigree analysis. Furthermore, the mutation frequency in sperm of Dmt-D mice increased significantly with age (28.0% at 17 weeks). The age dependence of the degree of expansion implies that mutations accumulate with time in spermatogenic stem cells. Similar rates of expansion per spermatogenic cycle in man would yield the large expansions observed in human diseases such as myotonic dystrophy type 1. Pedigree data showed a significant age-dependent bias toward repeat contraction in female transmissions and...Continue Reading

Citations

Nov 8, 2003·Trends in Molecular Medicine·Christopher E Pearson
Nov 25, 2003·Nucleic Acids Research·Elisabeth PiñeiroAntonia Velázquez
Jan 1, 2004·Molecular and Cellular Biology·Cédric SavouretGeneviève Gourdon
Mar 8, 2013·PLoS Genetics·Stéphanie ToméChristopher E Pearson
Mar 5, 2014·Asian Journal of Andrology·Ali A DabajaDarius A Paduch
Jan 21, 2009·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Judith R BrouwerBen A Oostra
Oct 6, 2005·Nature Reviews. Genetics·Christopher E PearsonJohn D Cleary
Feb 16, 2020·The Journal of Biological Chemistry·Alexandra N Khristich, Sergei M Mirkin
May 15, 2018·Clinical Genetics·L E Almaguer-MederosL Velázquez-Pérez
Jan 29, 2021·The Journal of Biological Chemistry·Alexandra N Khristich, Sergei M Mirkin
Mar 31, 2007·Science·Mark E Fortini

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