Preparation and validation of the first WHO international genetic reference panel for Fragile X syndrome
| Autor: | Trent Burgess, Rob Elles, David E. Barton, Malcolm Hawkins, J. Ross Hawkins, Chris Burns, Anna O'Grady, K. E. Wright, Jennifer Boyle, Elaine Gray, Simon C Ramsden, Michael Sweeney, Paul Metcalfe, Melanie Moore, Glyn Stacey |
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| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Male
Herpesvirus 4 Human Genotype Genetic Reference Panel Biology World Health Organization Article Fragile X Mental Retardation Protein 03 medical and health sciences medicine Genetics Humans Genetic Testing Lymphocytes Allele Genotyping FMR1 Genetics (clinical) Cell Line Transformed 030304 developmental biology Genetic testing 0303 health sciences Fragile X Tremor/Ataxia Syndrome medicine.diagnostic_test 030305 genetics & heredity DNA Reference Standards medicine.disease Human genetics 3. Good health Doenças Genéticas Fragile X syndrome Certified Reference Materials Fragile X Syndrome Mutation Female Erratum |
| Zdroj: | European Journal of Human Genetics; Vol 19 Europe PubMed Central |
| ISSN: | 1018-4813 |
| DOI: | 10.1038/ejhg.2010.135 |
| Popis: | Fragile X syndrome is the most common inherited form of mental retardation. It is caused by expansion of a trinucleotide (CGG)n repeat sequence in the 5′ untranslated region of the FMR1 gene, resulting in promoter hypermethylation and suppression of FMR1 transcription. Additionally, pre-mutation alleles in carrier males and females may result in Fragile X tremor ataxia syndrome and primary ovarian insufficiency, respectively. Fragile X is one of the most commonly requested molecular genetic tests worldwide. Quality assessment schemes have identified a wide disparity in allele sizing between laboratories. It is therefore important that clinical laboratories have access to characterized reference materials (RMs) to aid accurate allele sizing and diagnosis. With this in mind, a panel of genotyping RMs for Fragile X syndrome has been developed, which should be stable over many years and available to all diagnostic laboratories. Immortalized cell lines were produced by Epstein–Barr virus transformation of lymphocytes from consenting patients. Genomic DNA was extracted in bulk and RM aliquots were freeze-dried in glass ampoules. Twenty-one laboratories from seventeen countries participated in a collaborative study to assess their suitability. Participants evaluated the samples (blinded, in triplicate) in their routine methods alongside in-house and commercial controls. The panel of five genomic DNA samples was endorsed by the European Society of Human Genetics and approved as an International Standard by the Expert Committee on Biological Standardization at the World Health Organization. |
| Databáze: | OpenAIRE |
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