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Examination of factors associated with instability of the FMR1 CGG repeat.

Publication ,  Journal Article
Ashley-Koch, AE; Robinson, H; Glicksman, AE; Nolin, SL; Schwartz, CE; Brown, WT; Turner, G; Sherman, SL
Published in: Am J Hum Genet
September 1998

We examined premutation-female transmissions and premutation-male transmissions of the FMR1 CGG repeat to carrier offspring, to identify factors associated with instability of the repeat. First we investigated associations between parental and offspring repeat size. Premutation-female repeat size was positively correlated with the risk of having full-mutation offspring, confirming previous reports. Similarly, premutation-male repeat size was positively correlated with the daughter's repeat size. However, increasing paternal repeat size was associated also with both increased risk of contraction and decreased magnitude of the repeat-size change passed to the daughter. We hypothesized that the difference between the female and male transmissions was due simply to selection against full-mutation sperm. To test this hypothesis, we simulated selection against full-mutation eggs, by only examining premutation-female transmissions to their premutation offspring. Among this subset of premutation-female transmissions, associations between maternal and offspring repeat size were similar to those observed in premutation-male transmissions. This suggests that the difference between female and male transmissions may be due to selection against full-mutation sperm. Increasing maternal age was associated with increasing risk of expansion to the full mutation, possibly because of selection for smaller alleles within the offspring's soma over time; a similar effect of increasing paternal age may be due to the same selection process. Last, we have evidence that the reported association between offspring sex and risk of expansion may be due to ascertainment bias. Thus, female and male offspring are equally likely to inherit the full mutation.

Duke Scholars

Published In

Am J Hum Genet

DOI

ISSN

0002-9297

Publication Date

September 1998

Volume

63

Issue

3

Start / End Page

776 / 785

Location

United States

Related Subject Headings

  • X Chromosome
  • Trinucleotide Repeats
  • Sex Characteristics
  • Risk Assessment
  • Retrospective Studies
  • RNA-Binding Proteins
  • Prenatal Diagnosis
  • Nerve Tissue Proteins
  • Mutation
  • Maternal Age
 

Citation

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MLA
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Ashley-Koch, A. E., Robinson, H., Glicksman, A. E., Nolin, S. L., Schwartz, C. E., Brown, W. T., … Sherman, S. L. (1998). Examination of factors associated with instability of the FMR1 CGG repeat. Am J Hum Genet, 63(3), 776–785. https://doi.org/10.1086/302018
Ashley-Koch, A. E., H. Robinson, A. E. Glicksman, S. L. Nolin, C. E. Schwartz, W. T. Brown, G. Turner, and S. L. Sherman. “Examination of factors associated with instability of the FMR1 CGG repeat.Am J Hum Genet 63, no. 3 (September 1998): 776–85. https://doi.org/10.1086/302018.
Ashley-Koch AE, Robinson H, Glicksman AE, Nolin SL, Schwartz CE, Brown WT, et al. Examination of factors associated with instability of the FMR1 CGG repeat. Am J Hum Genet. 1998 Sep;63(3):776–85.
Ashley-Koch, A. E., et al. “Examination of factors associated with instability of the FMR1 CGG repeat.Am J Hum Genet, vol. 63, no. 3, Sept. 1998, pp. 776–85. Pubmed, doi:10.1086/302018.
Ashley-Koch AE, Robinson H, Glicksman AE, Nolin SL, Schwartz CE, Brown WT, Turner G, Sherman SL. Examination of factors associated with instability of the FMR1 CGG repeat. Am J Hum Genet. 1998 Sep;63(3):776–785.
Journal cover image

Published In

Am J Hum Genet

DOI

ISSN

0002-9297

Publication Date

September 1998

Volume

63

Issue

3

Start / End Page

776 / 785

Location

United States

Related Subject Headings

  • X Chromosome
  • Trinucleotide Repeats
  • Sex Characteristics
  • Risk Assessment
  • Retrospective Studies
  • RNA-Binding Proteins
  • Prenatal Diagnosis
  • Nerve Tissue Proteins
  • Mutation
  • Maternal Age