Trinucleotide repeats in the human genome: size distributions for all possible triplets and detection of expanded disease alleles in a group of Huntington disease individuals by the repeat expansion detection method
| Autor: | Uta Francke, N. Carolyn Schanen, Farid F. Chehab, Sigrun Hofferbert |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
Adult
Male congenital hereditary and neonatal diseases and abnormalities Population Biology Sensitivity and Specificity Genome Cell Line Gene Frequency Trinucleotide Repeats Huntington's disease Genetics medicine Humans Allele education Molecular Biology Allele frequency Alleles In Situ Hybridization Genetics (clinical) education.field_of_study Genome Human General Medicine medicine.disease nervous system diseases Huntington Disease Microsatellite Female Human genome Trinucleotide repeat expansion |
| Zdroj: | Human Molecular Genetics. 6:77-83 |
| ISSN: | 1460-2083 |
| DOI: | 10.1093/hmg/6.1.77 |
| Popis: | Using a modified Repeat Expansion Detection (RED) assay, that was optimized for individual oligonucleotides, unrelated individuals were systematically screened for maximal repeat sizes of each of the ten possible trinucleotide repeats. Cloned trinucleotide repeats were generated and used as standards for the detectability of single copy trinucleotide repeat fragments. When the size distributions of trinucleotide repeats were compared to previously reported data, significant differences were found for the CTT repeat, which corresponds to the expanded GAA repeat in Friedreich ataxia, as well as for ATT, CCT and GTT repeats. Since 30-35% of normal individuals have CTG/CAG trinucleotide repeat sizes of 180 bp or more, we investigated the question whether small-scale CTG/CAG repeat expansions are detectable on a population basis by using the RED technique. We blindly screened 20 HD probands with CAG expansions of the HD gene, ranging in size between 120 and 174 bp, and found that a shift to larger CAG size ranges is clearly detectable when comparing the distribution of maximal repeat sizes in the disease group to a control group. Our study, therefore, demonstrates that the application of the RED assay to a population of probands and a population of controls allows the detection of small-scale CTG/CAG repeat expansions in the size range of the expanded HD gene and present in a single allele. We also provide standards and control data for the detection of other trinucleotide repeat expansions. |
| Databáze: | OpenAIRE |
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