Revisiting Mendelian disorders through exome sequencing.
Summary of "Revisiting Mendelian disorders through exome sequencing."
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.
Department of Epidemiology and Public Health, Centre for Molecular Epidemiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore, firstname.lastname@example.org.
This article was published in the following journal.
Name: Human genetics
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/21331778
- DOI: http://dx.doi.org/10.1007/s00439-011-0964-2
Medical and Biotech [MESH] Definitions
High-throughput Nucleotide Sequencing
Techniques of nucleotide sequence analysis that increase the range, complexity, sensitivity, and accuracy of results by greatly increasing the scale of operations and thus the number of nucleotides, and the number of copies of each nucleotide sequenced. The sequencing may be done by analysis of the synthesis or ligation products, hybridization to preexisting sequences, etc.
Disorders of verbal and nonverbal communication caused by receptive or expressive LANGUAGE DISORDERS, cognitive dysfunction (e.g., MENTAL RETARDATION), psychiatric conditions, and HEARING DISORDERS.
State in which an individual perceives or experiences a sensation of unreality concerning the self or the environment; it is seen in disorders such as schizophrenia, affection disorders, organic mental disorders, and personality disorders. (APA, Thesaurus of Psychological Index Terms, 8th ed.)
Conditions characterized by disturbances of usual sleep patterns or behaviors. Sleep disorders may be divided into three major categories: DYSSOMNIAS (i.e. disorders characterized by insomnia or hypersomnia), PARASOMNIAS (abnormal sleep behaviors), and sleep disorders secondary to medical or psychiatric disorders. (From Thorpy, Sleep Disorders Medicine, 1994, p187)
Mendelian Randomization Analysis
The use of the GENETIC VARIATION of known functions or phenotypes to correlate the causal effects of those functions or phenotypes with a disease outcome.
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