Revisiting Mendelian disorders through exome sequencing.

TitleRevisiting Mendelian disorders through exome sequencing.
Publication TypeJournal Article
Year of Publication2011
AuthorsKu C-S, Naidoo N, Pawitan Y
JournalHuman genetics
Date Published2011 Apr
KeywordsAbnormalities, Multiple, Exons, Face, Genetic Diseases, Inborn, Genetic Predisposition to Disease, Genome-Wide Association Study, Hematologic Diseases, Humans, Limb Deformities, Congenital, Mandibulofacial Dysostosis, Micrognathism, Mutation, Sequence Analysis, DNA, Vestibular Diseases

Over the past several years, more focus has been placed on dissecting the genetic basis of complex diseases and traits through genomei-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. Exomei 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 genesi 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.

Alternate JournalHum. Genet.
Citation Key929
PubMed ID21331778