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.
Affiliation
Department of Epidemiology and Public Health, Centre for Molecular Epidemiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore, g0700040@nus.edu.sg.
Journal Details
This article was published in the following journal.
Name: Human genetics
ISSN: 1432-1203
Pages:
Links
- 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.
Communication Disorders
Disorders of verbal and nonverbal communication caused by receptive or expressive LANGUAGE DISORDERS, cognitive dysfunction (e.g., MENTAL RETARDATION), psychiatric conditions, and HEARING DISORDERS.
Depersonalization
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.)
Sleep Disorders
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.
PubMed Articles
Exome sequencing: an efficient strategy for identifying the causative genes of monogenic disorders.
The development of new generation sequencing technologies has brought new opportunities for the study of diseases. Exome sequencing has shown to be an effective, rapid, high performance technique that...
Exome sequencing in an SCA14 family demonstrates its utility in diagnosing heterogeneous diseases.
Genetic heterogeneity is common in many neurologic disorders. This is particularly true for the hereditary ataxias where at least 36 disease genes or loci have been described for spinocerebellar ataxi...
Accelerated aging syndromes represent a valuable source of information about the molecular mechanisms involved in normal aging. Here, we describe a progeroid syndrome that partially phenocopies Hutchi...
Exome Sequencing: The Sweet Spot Before Whole Genomes.
The development of massively-parallel sequencing technologies, coupled with new massively-parallel DNA enrichment technologies (genomic capture) has allowed the sequencing of targeted regions of the h...
Exome sequencing as a diagnostic tool in a case of undiagnosed juvenile-onset GM1-gangliosidosis.
OBJECTIVE: To utilize high-throughput sequencing to determine the etiology of juvenile-onset neurodegeneration in a 19-year-old woman with progressive motor and cognitive decline. METHODS: Exome seque...
Clinical Trials
Exome Sequencing in Autistic Spectrum Disorder
Background: - Research into the genetic causes of autism spectrum disorder (ASD) involves studies of the DNA of children with autism. New DNA sequencing technology allows research...
Whole Genome Medical Sequencing for Genome Discovery
Background: - A number of rare inherited diseases affect only a few patients, and the genetic causes of these conditions remain unknown. Researchers are studying the use of a new technolo...
Trisomy of Chromosome 21 Diagnosis by High Output Sequencing
Demonstrate that the High output shotgun sequencing of the foetal DNA in the maternal blood could allow a complete discrimination between the mothers of a trisomic fetus 21 or a DISOMIQUE...
Genetic etiology in schizophrenia is widely accepted. However, many chromosomal sites were shown to characterize the families of patients with schizophrenia. This is probably due to the hi...
ClinSeq: A Large-Scale Medical Sequencing Clinical Research Pilot Study
This study will examine genome sequencing in clinical research. Genome sequencing is a process in which researchers analyze (or sequence) part or all of the genome from a single person. Th...
