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Systems biology ana...
Systems biology analysis of human genomes points to key pathways conferring spina bifida risk
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- Aguiar-Pulido, Vanessa (författare)
- Weill Cornell Medicine
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- Wolujewicz, Paul (författare)
- Weill Cornell Medicine
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- Martinez-Fundichely, Alexander (författare)
- Weill Cornell Medicine
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- Elhaik, Eran (författare)
- Lund University,Lunds universitet,Molekylär cellbiologi,Biologiska institutionen,Naturvetenskapliga fakulteten,Bioinformatik,Forskargrupper vid Lunds universitet,Molecular Cell Biology,Department of Biology,Faculty of Science,Bioinformatics,Lund University Research Groups
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- Thareja, Gaurav (författare)
- Weill Cornell Medicine, Qatar
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- Abdel Aleem, Alice (författare)
- Weill Cornell Medicine, Qatar
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- Chalhoub, Nader (författare)
- Weill Cornell Medicine, Qatar
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- Cuykendall, Tawny (författare)
- Weill Cornell Medicine
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- Al-Zamer, Jamel (författare)
- Hamad Medical Corporation
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- Lei, Yunping (författare)
- Baylor College of Medicine
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- El-Bashir, Haitham (författare)
- Hamad Medical Corporation
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- Musser, James M (författare)
- Methodist Hospital Houston
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- Al-Kaabi, Abdulla (författare)
- Weill Cornell Medicine, Qatar
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- Shaw, Gary M (författare)
- Stanford University School of Medicine
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- Khurana, Ekta (författare)
- Weill Cornell Medicine
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- Suhre, Karsten (författare)
- Weill Cornell Medicine, Qatar
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- Mason, Christopher E (författare)
- Weill Cornell Medicine
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- Elemento, Olivier (författare)
- Weill Cornell Medicine
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- Finnell, Richard H (författare)
- Baylor College of Medicine
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- Ross, M Elizabeth (författare)
- Weill Cornell Medicine
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(creator_code:org_t)
- 2021-12-16
- 2021
- Engelska 10 s.
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 118:51
- Relaterad länk:
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http://dx.doi.org/10...
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https://doi.org/10.1...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Spina bifida (SB) is a debilitating birth defect caused by multiple gene and environment interactions. Though SB shows non-Mendelian inheritance, genetic factors contribute to an estimated 70% of cases. Nevertheless, identifying human mutations conferring SB risk is challenging due to its relative rarity, genetic heterogeneity, incomplete penetrance, and environmental influences that hamper genome-wide association studies approaches to untargeted discovery. Thus, SB genetic studies may suffer from population substructure and/or selection bias introduced by typical candidate gene searches. We report a population based, ancestry-matched whole-genome sequence analysis of SB genetic predisposition using a systems biology strategy to interrogate 298 case-control subject genomes (149 pairs). Genes that were enriched in likely gene disrupting (LGD), rare protein-coding variants were subjected to machine learning analysis to identify genes in which LGD variants occur with a different frequency in cases versus controls and so discriminate between these groups. Those genes with high discriminatory potential for SB significantly enriched pathways pertaining to carbon metabolism, inflammation, innate immunity, cytoskeletal regulation, and essential transcriptional regulation consistent with their having impact on the pathogenesis of human SB. Additionally, an interrogation of conserved noncoding sequences identified robust variant enrichment in regulatory regions of several transcription factors critical to embryonic development. This genome-wide perspective offers an effective approach to the interrogation of coding and noncoding sequence variant contributions to rare complex genetic disorders.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
Nyckelord
- Case-Control Studies
- Genetic Predisposition to Disease
- Genome, Human
- Genome-Wide Association Study
- Humans
- Spinal Dysraphism/genetics
- Systems Biology
- Transcription Factors/genetics
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Aguiar-Pulido, V ...
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Wolujewicz, Paul
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Martinez-Fundich ...
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Elhaik, Eran
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Thareja, Gaurav
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Abdel Aleem, Ali ...
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visa fler...
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Chalhoub, Nader
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Cuykendall, Tawn ...
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Al-Zamer, Jamel
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Lei, Yunping
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El-Bashir, Haith ...
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Musser, James M
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Al-Kaabi, Abdull ...
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Shaw, Gary M
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Khurana, Ekta
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Suhre, Karsten
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Mason, Christoph ...
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Elemento, Olivie ...
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Finnell, Richard ...
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Ross, M Elizabet ...
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