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. 2002 Jun;70(6):1532-44.
doi: 10.1086/340846. Epub 2002 May 3.

Paternally transmitted FMR1 alleles are less stable than maternally transmitted alleles in the common and intermediate size range

Amy K Sullivan  1 , Dana C Crawford, Elizabeth H Scott, Mary L Leslie, Stephanie L Sherman
Affiliations

Paternally transmitted FMR1 alleles are less stable than maternally transmitted alleles in the common and intermediate size range

Amy K Sullivan et al. Am J Hum Genet. 2002 Jun.

Abstract

Fragile X syndrome, a form of X-linked mental retardation, results from the hyperexpansion of a CGG trinucleotide repeat located in the 5' untranslated region of the fragile X mental retardation (FMR1) gene. Relatively little is known about the initial mutation that causes a stable allele to become unstable and, eventually, to expand to the full mutation. In the present study, we have examined 1,452 parent-child transmissions of alleles of common (< or =39 repeats) or intermediate (40-59 repeats) sizes to study the initial mutation events. Of these, 201 have been sequenced and haplotyped. Using logistic regression analysis, we found that parental origin of transmission, repeat size (for unsequenced alleles), and number of the 3' CGGs (for sequenced alleles) were significant risk factors for repeat instability. Interestingly, transmission of the repeat through males was less stable than that through females, at the common- and intermediate-size level. This pattern differs from that seen for premutation-size alleles: paternally transmitted alleles are far more stable than maternally transmitted alleles. This difference that depends on repeat size suggests either a different mutational mechanism of instability or an increase in selection against sperm as their repeat size increases.

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Figures

Figure 1
Figure 1
Percentages of unstable maternal and paternal transmissions and the corresponding predicted risk for instability, according to repeat size.
Figure 2
Figure 2
Percentages of unstable maternal and paternal transmissions and the corresponding predicted risk for instability based on the length of the 3′ end.
Figure 3
Figure 3
Magnitude of the change in repeat size of maternal and paternal unstable transmissions.
See this image and copyright information in PMC

References

Electronic-Database Information

    1. Online Mendelian Inheritance in Man (OMIM), http://www.ncbi.nlm.nih.gov/Omim/ (for fragile X syndrome [MIM 309550])

References

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