Journal article

Revisiting Mendelian disorders through exome sequencing.

Toplak N, Frenkel J, Ozen S, Lachmann H, Woo P, Koné-Paut I, De Benedetti F, Neven B, Hofer M, Dolezalova P, Kümmerle-Deschner J, Touitou I, Hentgen V, Simon A, Girschick H, Rose C, Wouters C, Vesely R, Arostegui J, Stojanov S, Ozgodan H, Martini A, Ruperto N, Gattorno M ...see all

Annals of the Rheumatic Diseases, vol. 71, issue 7 (2012) pp. 1177-1182 Published by BMJ Publishing Group Ltd

  • 1

    Readers

    Mendeley users who have this article in their library.
  • N/A

    Citations

    Citations of this article.
Sign in to save reference

Abstract

Over the past several years, more focus has been placed on dissecting the genetic basis of complex diseases and traits through genome-wide association studies. In contrast, Mendelian disorders have received little attention mainly due to the lack of newer and more powerful methods to study these disorders. Linkage studies have previously been the main tool to elucidate the genetics of Mendelian disorders; however, extremely rare disorders or sporadic cases caused by de novo variants are not amendable to this study design. Exome sequencing has now become technically feasible and more cost-effective due to the recent advances in high-throughput sequence capture methods and next-generation sequencing technologies which have offered new opportunities for Mendelian disorder research. Exome sequencing has been swiftly applied to the discovery of new causal variants and candidate genes for a number of Mendelian disorders such as Kabuki syndrome, Miller syndrome and Fowler syndrome. In addition, de novo variants were also identified for sporadic cases, which would have not been possible without exome sequencing. Although exome sequencing has been proven to be a promising approach to study Mendelian disorders, several shortcomings of this method must be noted, such as the inability to capture regulatory or evolutionary conserved sequences in non-coding regions and the incomplete capturing of all exons.

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document

Authors

  • Natasa Toplak

  • Joost Frenkel

  • Seza Ozen

  • Helen J Lachmann

  • Patricia Woo

  • Isabelle Koné-Paut

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free