Author Interviews, Autism, Genetic Research, NIH / 16.08.2016
Better, Cheaper Assay for Fragile X Syndrome Detection
MedicalResearch.com Interview with:
Karen Usdin, Ph. D.
Senior Investigator
Chief, Gene Structure and Disease Section
Laboratory of Cell and Molecular Biology
National Institute of Diabetes, Digestive and Kidney Diseases
National Institutes of Health
Bethesda MD 20892
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Our laboratory is interested in the causes and consequences of the unusual repeat expansion mutation that causes the Fragile X-related disorders. However these disorders are challenging to study, in part because the repeat tract is difficult to amplify by PCR. This makes monitoring of repeat length, as well as other factors we are interested in such as methylation status and the presence of AGG interruptions, quite difficult.
In our experience, both repeat number and methylation status are very variable in patient stem cells and in disease-relevant cell types derived from them. This variability arises because the repeat is prone to both expansion and contraction and because at different times there can be selection for smaller alleles or against unmethylated ones. Thus the frequent monitoring of repeat length and methylation status is critical for work with patient cells, particularly when those cells are to be used for drug screening or to examine the consequences of expansion.
While other assays are available to determine one or more of these parameters, some are cumbersome to use or lack the necessary robustness and sensitivity, whilst others are prohibitively expensive for routine laboratory work. We thus saw a need for assays that are robust, sensitive and cost-effective for preclinical studies.
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