{"id":604,"date":"2020-09-10T00:02:40","date_gmt":"2020-09-09T21:02:40","guid":{"rendered":"https:\/\/f-genetics.com\/?post_type=test&p=604"},"modified":"2023-01-17T23:16:34","modified_gmt":"2023-01-17T20:16:34","slug":"exom-2","status":"publish","type":"test","link":"https:\/\/f-genetics.com\/en\/exom-2\/","title":{"rendered":"Exome sequencing"},"content":{"rendered":"

Technical overview<\/h2>
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Overview<\/div>
Indications<\/div>
Technology of testing<\/div>
Analysis options<\/div><\/div><\/div>
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\u2192<\/div>
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Exome sequencing is a targeted, next generation sequencing (NGS) method that is restricted to the areas of the genome that encode protein. Exome covers approximately 1% of the genome but contains about 85% of the disease-causing nucleotide sequence variants.<\/p>\n\n\n

For bioinformaticians trying to identify genes involved in more than 6,800 rare diseases among the plethora of findings, exome sequencing allows rapid and cost-effective identification of single-nucleotide polymorphisms<\/span> and indels (small insertions and deletions).<\/p>\n\n\n

Both inherited and de novo mutations<\/span> can be identified, which may explain the heritability of Mendelian and complex disorders. In some cases, exome analysis can detect copy number variation (CNV).<\/p>\n<\/div>\n\n\n\n

1%<\/span>of the genome is covered by the exome<\/span><\/p>\n\n\n

85%<\/span>of nucleotide sequence variants<\/span><\/p>\n\n\n

6800<\/span>rare diseases<\/span><\/p>\n<\/div>\n<\/div>\n<\/div>\n\n\n\n

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In diagnoses with clinical heterogeneity<\/p>\n\n\n\n

Examples: epilepsy, epileptic encephalopathies, muscular dystrophies\/muscle disorders, ataxia, neuropathies, cardiomyopathies, connective tissue dysplasias, immunodeficiencies, deafness, blindness when major syndrome-associated variants are excluded<\/p>\n<\/div>\n\n\n\n

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Atypical clinical manifestations or phenotypes. Clinically, it is difficult to isolate a specific gene or group of genes<\/p>\n\n\n\n

Example: Hereditary ataxias, atypical parkinsonism<\/p>\n<\/div>\n\n\n\n

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In genetically heterogeneous conditions where there's a high number of genes involved in the disease<\/p>\n\n\n\n

Examples: mental retardation and severe immunodeficiency, autism<\/p>\n<\/div>\n\n\n\n

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In the case of problematic heredity, when other genetic tests have failed to establish a diagnosis<\/p>\n\n\n\n

Example: patient with neuropsychiatric retardation and similarly affected siblings, with a negative chromosomal micro-matrix analysis.<\/p>\n<\/div>\n\n\n\n

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On the importance of clinical information<\/div>
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Different variants can be found during the interpretation of whole exome sequencing data - known pathogenic or benign, with unknown clinical significance or rare variants not previously described. In order to determine clinical significance and to match the variant found to a genetic disease, it is necessary to have as much clinical information about the proband and his or her immediate family members as possible. Withholding any clinical information, including the patient's family history, may affect the test results and their interpretation. Lack of clinical information may lead to exclusion of genetic variants that may be relevant to the patient and the assignment of incorrect clinical significance to identified variants.<\/p>\n<\/div><\/div>\n<\/div>\n\n\n\n

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DNA isolation \u2192 DNA library preparation \u2192 Region enrichment \u2192 Sequencing \u2192 Bioinformatics data processing<\/h3>\n\n\n\n
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\u00abTrio\u00bb<\/h3>\n\n\n\n
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Includes sequence analysis of the entire exome of the patient, the parents or other family members.<\/p>\n<\/div>\n\n\n\n

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The triple-pronged approach in exome sequencing improves diagnostic accuracy by facilitating the analysis of nucleotide sequence variants and enabling the detection of de novo<\/em> mutations that underlie many diseases with early manifestation and severe course.<\/p>\n<\/div>\n<\/div>\n\n\n\n

\u00abClinical exome\u00bb<\/h3>\n\n\n\n
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Sequencing exons of only those genes whose mutations lead to the development of known diseases<\/p>\n<\/div>\n\n\n\n

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More than 4,700 such genes have been described in the OMIM database so far. Although this type of analysis is cheaper, the list of genes is constantly being updated and is therefore less informative.<\/p>\n<\/div>\n<\/div>\n\n\n\n

Panel sequencing<\/h3>\n\n\n\n
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Based on the analysis of a group of genes combined into multigene panels. This type of diagnosis focuses on a specific syndromic indication.<\/p>\n<\/div>\n\n\n\n

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Randomised results are unlikely with this approach. Panels go out of use as new genes associated with the disease are discovered or atypical symptoms are identified that overlap with indications for the use of a particular panel.<\/p>\n<\/div>\n<\/div>\n\n\n\n

View a comparison table<\/div>
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\"\"Algorithm for molecular genetic diagnostics (ru) 493 KB, PDF<\/i><\/span><\/a><\/div>\n\t\t\t\t\t\t\t
\"\"Download page (ru) 2 MB, PDF<\/i><\/span><\/a><\/div>\n\t\t\t\n\t\t\t\t\t\t\t\t\t\t
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