UCL  IRIS
Institutional Research Information Service
UCL Logo
Please report any queries concerning the funding data grouped in the sections named "Externally Awarded" or "Internally Disbursed" (shown on the profile page) to your Research Finance Administrator. Your can find your Research Finance Administrator at https://www.ucl.ac.uk/finance/research/rs-contacts.php by entering your department
Please report any queries concerning the student data shown on the profile page to:

Email: portico-services@ucl.ac.uk

Help Desk: http://www.ucl.ac.uk/ras/portico/helpdesk
Publication Detail
Characterisation and Validation of Insertions and Deletions in 173 Patient Exomes
  • Publication Type:
    Journal article
  • Publication Sub Type:
    Journal Article
  • Authors:
    Lescai F, Bonfiglio S, Bacchelli C, Chanudet E, Waters A, Sisodiya SM, Kasperavičiute D, Williams J, Harold D, Hardy J, Kleta R, Cirak S, Williams R, Achermann JC, Anderson J, Kelsell D, Vulliamy T, Houlden H, Wood N, Sheerin U, Tonini GP, Mackay D, Hussain K, Sowden J, Kinsler V, Osinska J, Brooks T, Hubank M, Beales P, Stupka E
  • Publication date:
    14/12/2012
  • Journal:
    PLoS ONE
  • Volume:
    7
  • Issue:
    12
  • Status:
    Published
Abstract
Recent advances in genomics technologies have spurred unprecedented efforts in genome and exome re-sequencing aiming to unravel the genetic component of rare and complex disorders. While in rare disorders this allowed the identification of novel causal genes, the missing heritability paradox in complex diseases remains so far elusive. Despite rapid advances of next-generation sequencing, both the technology and the analysis of the data it produces are in its infancy. At present there is abundant knowledge pertaining to the role of rare single nucleotide variants (SNVs) in rare disorders and of common SNVs in common disorders. Although the 1,000 genome project has clearly highlighted the prevalence of rare variants and more complex variants (e.g. insertions, deletions), their role in disease is as yet far from elucidated. We set out to analyse the properties of sequence variants identified in a comprehensive collection of exome re-sequencing studies performed on samples from patients affected by a broad range of complex and rare diseases (N = 173). Given the known potential for Loss of Function (LoF) variants to be false positive, we performed an extensive validation of the common, rare and private LoF variants identified, which indicated that most of the private and rare variants identified were indeed true, while common novel variants had a significantly higher false positive rate. Our results indicated a strong enrichment of very low-frequency insertion/deletion variants, so far under-investigated, which might be difficult to capture with low coverage and imputation approaches and for which most of study designs would be under-powered. These insertions and deletions might play a significant role in disease genetics, contributing specifically to the underlining rare and private variation predicted to be discovered through next generation sequencing. © 2012 Lescai et al.
Publication data is maintained in RPS. Visit https://rps.ucl.ac.uk
 More search options
UCL Researchers Show More
Author
ICH Genetics & Genomic Medicine Prog
Author
ICH Development Bio & Cancer Prog
Author
ICH Genetics & Genomic Medicine Prog
Author
ICH Genetics & Genomic Medicine Prog
Author
Neurodegenerative Diseases
Author
Department of Neuromuscular Diseases
Author
ICH Genetics & Genomic Medicine Prog
Author
Clinical & Experimental Epilepsy
Author
ICH Development Bio & Cancer Prog
University College London - Gower Street - London - WC1E 6BT Tel:+44 (0)20 7679 2000

© UCL 1999–2011

Search by