Author:
Annear Dale J.,Vandeweyer Geert,Elinck Ellen,Sanchis-Juan Alba,French Courtney E.,Raymond Lucy,Kooy R. Frank
Abstract
AbstractExpanded CGG-repeats have been linked to neurodevelopmental and neurodegenerative disorders, including the fragile X syndrome and fragile X-associated tremor/ataxia syndrome (FXTAS). We hypothesized that as of yet uncharacterised CGG-repeat expansions within the genome contribute to human disease. To catalogue the CGG-repeats, 544 human whole genomes were analyzed. In total, 6101 unique CGG-repeats were detected of which more than 93% were highly variable in repeat length. Repeats with a median size of 12 repeat units or more were always polymorphic but shorter repeats were often polymorphic, suggesting a potential intergenerational instability of the CGG region even for repeats units with a median length of four or less. 410 of the CGG repeats were associated with known neurodevelopmental disease genes or with strong candidate genes. Based on their frequency and genomic location, CGG repeats may thus be a currently overlooked cause of human disease.
Funder
Marguerite-Marie Delacroix foundation
Fonds Wetenschappelijk Onderzoek - Vlaanderen
NIHR BioResource
Rosetrees Trust, Newton Trust, National Institute for Health Research (NIHR) for the Cambridge Biomedical Research Centre
Methusalem-OEC grant – “GENOMED”
Publisher
Springer Science and Business Media LLC
Reference49 articles.
1. Tang, H. et al. Profiling of short-tandem-repeat disease alleles in 12,632 human whole genomes. Am. J. Hum. Genet. 101, 700–715 (2017).
2. McMahon, K. et al. Neurogenetics in the genome era. In Swaiman’s Pediatric Neurology (ed. Swaiman, K. et al) 257–267 (Elsevier, Amsterdam, 2017).
3. Nelson, D. L., Orr, H. T. & Warren, S. T. The unstable repeats–three evolving faces of neurological disease. Neuron 77, 825–843 (2013).
4. Hagerman, R. J. et al. Fragile X syndrome. Nat. Rev. Dis. Primers 3, 17065 (2017).
5. Willemsen, R. & Kooy, R. F. Clinics, diagnosis, epidemiology, molecular mechanics, and models. In Fragile X Syndrome: From Genetics to Targeted Treatment. (ed. Willemsen, R. & Kooy, R.) 3–18 (Elsevier, Amsterdam, 2017).
Cited by
30 articles.
订阅此论文施引文献
订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献