Genome-wide investigation identifies a rare copy-number variant burden associated with human spina bifida
| العنوان: | Genome-wide investigation identifies a rare copy-number variant burden associated with human spina bifida |
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| المؤلفون: | Karsten Suhre, Alice AbdelAleem, Olivier Elemento, Gary M. Shaw, Vanessa Aguiar-Pulido, Vidya Nair, Richard H. Finnell, M. Elizabeth Ross, Paul Wolujewicz, Gaurav Thareja |
| المصدر: | Genetics in Medicine |
| بيانات النشر: | Nature Publishing Group US, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, DNA Copy Number Variations, Biology, Genome, Polymorphism, Single Nucleotide, Article, Structural variation, 03 medical and health sciences, Exon, 0302 clinical medicine, medicine, Humans, Copy-number variation, Gene, Spinal Dysraphism, Genetics (clinical), Genetics, Neural tube defect, Genetic disorder, medicine.disease, Genetic architecture, 030104 developmental biology, Case-Control Studies, 030217 neurology & neurosurgery, Genome-Wide Association Study |
| الوصف: | Purpose Next-generation sequencing has implicated some risk variants for human spina bifida (SB), but the genome-wide contribution of structural variation to this complex genetic disorder remains largely unknown. We examined copy-number variant (CNV) participation in the genetic architecture underlying SB risk. Methods A high-confidence ensemble approach to genome sequences (GS) was benchmarked and employed for systematic detection of common and rare CNVs in two separate ancestry-matched SB case–control cohorts. Results SB cases were enriched with exon disruptive rare CNVs, 44% of which were under 10 kb, in both ancestral populations (P = 6.75 × 10−7; P = 7.59 × 10−4). Genes containing these disruptive CNVs fall into molecular pathways, supporting a role for these genes in SB. Our results expand the catalog of variants and genes with potential contribution to genetic and gene–environment interactions that interfere with neurulation, useful for further functional characterization. Conclusion This study underscores the need for genome-wide investigation and extends our previous threshold model of exonic, single-nucleotide variation toward human SB risk to include structural variation. Since GS data afford detection of CNVs with greater resolution than microarray methods, our results have important implications toward a more comprehensive understanding of the genetic risk and mechanisms underlying neural tube defect pathogenesis. |
| اللغة: | English |
| تدمد: | 1530-0366 1098-3600 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5e7e94a17e489d96cd787e1ac1c387fd http://europepmc.org/articles/PMC8257499 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....5e7e94a17e489d96cd787e1ac1c387fd |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15300366 10983600 |
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