Journal Article

The Role of Size, Sequence and Haplotype in the Stability of <i>FRAXA</i> and <i>FRAXE</i> Alleles during Transmission

Anna Murray, James N. Macpherson, Michelle C. Pound, Andrea Sharrock, Sheila A. Youings, Nick R. Dennis, Nicky McKechnie, Paul Linehan, Newton E. Morton and Patricia A. Jacobs

in Human Molecular Genetics

Volume 6, issue 2, pages 173-184
Published in print February 1997 | ISSN: 0964-6906
Published online February 1997 | e-ISSN: 1460-2083 | DOI:
The Role of Size, Sequence and Haplotype in the Stability of FRAXA and FRAXE Alleles during Transmission

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Factors involved in the stability of trinucleotide repeats during transmission were studied in 139 families in which a full mutation, premutation or intermediate allele at either FRAXA or FRAXE was segregating. The transmission of alleles at FRAXA, FRAXE and four microsatellite loci were recorded for all individuals. Instability within the minimal and common ranges (0–40 repeats for FRAXA, 0–30 repeats for FRAXE) was extremely rare; only one example was observed, an increase in size at FRAXA from 29 to 39 repeats. Four FRAXA and three FRAXE alleles in the intermediate range (41–60 repeats for FRAXA, 31–60 repeats for FRAXE) were unstably transmitted. Instability was more frequent for FRAXA intermediate alleles that had a tract of pure CGG greater than 37 although instability only occurred in two of 13 such transmissions: the changes observed were limited to only one or two repeats. Premutation FRAXA alleles over 100 repeats expanded to a full mutation during female transmission in 100% of cases, in agreement with other published series. There was no clear correlation between haplotype and probability of expansion of FRAXA premutations. Instability at FRAXA or FRAXE was more often observed in conjunction with a second instability at an independent locus suggesting general genomic instability as a possible mechanism by which at least some FRAXA and FRAXE mutations arise.

Journal Article.  7289 words.  Illustrated.

Subjects: Genetics and Genomics

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