Genetic epidemiology of the Fragile X region
Genetic epidemiology of the Fragile X region
Prevalence of the disease in both its full mutation and premutation states was estimated. Confirmation that premutation alleles predispose to premature ovarian failure in this sample was extended to show the absence of any correlation between repeat size and age of onset. The data were investigated for evidence of a parent of origin effect at FMR1 and no supporting evidence was found. Phenotypic effects of the expanded repeat were shown to extend into the intermediate sized repeat range causing cognitive deficit. Combining evidence for phenotypic effects being associated with premutations and intermediates suggests there may be a spectrum of disorders related to the FMR1 triplet expansion in a manner analogous to some other triplet repeat diseases.
Haplotype data were investigated to study linkage disequilibrium in the region. Microsatellite haplotype groups were formulated and marker by marker allelic association was used to describe linkage disequilibrium in the area. This process yields information on regional recombination hot and cold spots. Results indicate a marker density of one SNP per one hundred kilobases should be informative for mapping in this area. Association of expanded FMR1 alleles with other expansion mutations in the area were investigated and shown to be positive. Properties of the associated haplotypes were examined and we speculate on the possibility of concatenated mutation being the responsible mechanism.
The first linkage disequilibrium map of this region was created using a panel of single nucleotide polymorphisms (SNPs) and confirmed the region to have a relatively low level of recombination compared to an estimated genome average. Detailed information on recombination in the FMR1 region was used to conduct a phylogenetic study using the SNP data. Resultant trees are described and annotated and offer a highly detailed and informative grouping system for fragile X haplotypes.
University of Southampton
Ennis, Sarah
87e595ad-64d8-4897-99f8-c9b258fbe214
2003
Ennis, Sarah
87e595ad-64d8-4897-99f8-c9b258fbe214
Ennis, Sarah
(2003)
Genetic epidemiology of the Fragile X region.
University of Southampton, Doctoral Thesis.
Record type:
Thesis
(Doctoral)
Abstract
Prevalence of the disease in both its full mutation and premutation states was estimated. Confirmation that premutation alleles predispose to premature ovarian failure in this sample was extended to show the absence of any correlation between repeat size and age of onset. The data were investigated for evidence of a parent of origin effect at FMR1 and no supporting evidence was found. Phenotypic effects of the expanded repeat were shown to extend into the intermediate sized repeat range causing cognitive deficit. Combining evidence for phenotypic effects being associated with premutations and intermediates suggests there may be a spectrum of disorders related to the FMR1 triplet expansion in a manner analogous to some other triplet repeat diseases.
Haplotype data were investigated to study linkage disequilibrium in the region. Microsatellite haplotype groups were formulated and marker by marker allelic association was used to describe linkage disequilibrium in the area. This process yields information on regional recombination hot and cold spots. Results indicate a marker density of one SNP per one hundred kilobases should be informative for mapping in this area. Association of expanded FMR1 alleles with other expansion mutations in the area were investigated and shown to be positive. Properties of the associated haplotypes were examined and we speculate on the possibility of concatenated mutation being the responsible mechanism.
The first linkage disequilibrium map of this region was created using a panel of single nucleotide polymorphisms (SNPs) and confirmed the region to have a relatively low level of recombination compared to an estimated genome average. Detailed information on recombination in the FMR1 region was used to conduct a phylogenetic study using the SNP data. Resultant trees are described and annotated and offer a highly detailed and informative grouping system for fragile X haplotypes.
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Published date: 2003
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Local EPrints ID: 464963
URI: http://eprints.soton.ac.uk/id/eprint/464963
PURE UUID: 439a6b88-59b3-480d-a0d5-e543e3ac4e32
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Date deposited: 05 Jul 2022 00:13
Last modified: 05 Jul 2022 00:13
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Author:
Sarah Ennis
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