Exome sequencing

Whole Exome Sequencing (WES)

Free shipping

Across Georgia

Up to 45 days

Test duration

Raw data provided

Free of charge, the format is .fastq

One time in your life

You can use the data for analysis when it`s necessary in the future

Exome sequencing overview

←

→

Genetic data is a sort of instruction for each body cell, that contains the mechanism of cell differentiation and functioning. This data is kept in the form of DNA molecules, which consist of four chemical compounds (bases) — adenine (A), thymine(T), cytosine (C) and guanine(G).

This sequence change can lead to misrepresentation of important data, disruption of normal cellular mechanisms and the development of diseases.

Sequentially connected to one another, these bases serve as keepers of information that is received from parents and is transmitted to children in a form understandable to our cells.

The human body consists of cells and cells contain DNA. Genes give information for the synthesis of all proteins in the organism

All the genetic data of organism is the genome, and it is recorded as a DNA molecule and represented by a sequence that is made up of over 3.2 billion bases. However, only 1% (30 million base pairs) of this sequence forms the exome.

Exome is only the part of the genome that is responsible for protein synthesis in the organism.

For clinical purposes, in most cases, data obtained as a result of the exome sequencing is sufficient.

More than 80% of all disease-associated mutations are mutations in the exome

Indications for the study

As a first-line research when it is assumed genetically heterogeneous diseases (several genes are presumably involved in a particular disease) and to clarify the prognosis of the course of the disease, for example:
- blindness,
- immunological disorders,
- complex dysmorphism,
- cardiomyopathy,
- metabolic disorders,
- connective tissue disorders,
- neuropsychiatric disorders,
- autism spectrum disorders,
- epilepsy.
When a delay in the development of undifferentiated genesis is recognised.
For children with multiple congenital anomalies, neuropsychiatric disorders and convulsions.
For a fetus with an abnormality detected by ultrasound, when molecular analysis (CMA) and cytogenetic test cannot give an ultimate diagnosis.
In the postnatal period conducting a comprehensive diagnosis in the postnatal period.

To interpret the results of exome sequencing, a consultation of a geneticist is required, regardless of the test result.

Characteristics of the study

The set of symptoms in some patients does not allow the clinician to establish an accurate diagnosis.

A step-by-step diagnostic strategy is often chosen, that makes a study difficult, time-consuming and expensive in such cases. Besides, delayed diagnosis can influence significantly on the quality of life and patient’s condition.

Learn more about routine molecular assays

Conventional molecular testing of patients with genetic disorders often relies on the study of a single gene or a panel (set) of genes.Though, it is estimated that up to half of the patients do not receive a diagnosis, and after such testing, it may take several years without establishing a definitive diagnosis.

With full-exome sequencing, there are most often several findings that are rare or even never met in other patients. Such variants are variants with uncertain clinical significance (VUS or VOUS). For them, one can only assume how «harmful» they can be, and treat them with extreme caution. Most of these rare variants do not lead to the appearance of any diseases.

In order to understand whether such a variation could cause the disease, it is extremely important to obtain specific and detailed clinical information from proband and relatives when performing exomic sequencing.

How does exome sequencing work in details?

Exome sequencing is a widely used next generation sequencing (NGS) method that reads certain parts of each gene that are considered to be most important for pathology recognition. The parts are called exons.

These «reads» contain large amounts of genetic sequence data that would take hundreds of hours to manually analyze.

For this reason, computer programs are used to quickly detect changes in the DNA sequence.

Tremendous list of identified variants is then «interpreted» by comparing the results with databases where known or suspected to be associated with genetic diseases variants are enumerate. Interpretation, as well as sequence analysis, is a comprehensive and time-consuming stage of exome sequencing, since it involves many specialist’s labor to determine the significance of each detected variant.

Exome sequencing process

Pros of exome sequencing

Exome sequencing reads simultaneously all protein-coding regions in the genome in comparison with panel sequencing, originally a more targeted genetic testing focused on a limited set of predefined genes.

Learn more about panel sequencing

Such sequencing is based on the analysis of a group of genes combined into multigene panels. This type of diagnosis is focused on a specific syndromic indication, random results are unlikely with this approach. Panels fall out of use as new disease-related genes are discovered or atypical symptoms are identified that overlap with indications for the use of a particular panel.

There is also a reduced exome analysis, «clinical exome», when only a subset of the coding sequences that are well studied in relation to monogenic diseases are looked at. Despite the fact that this type of analysis is cheaper, the list of genes associated with the development of diseases is constantly expanding, therefore, the «clinical exome» is less informative.

Exome sequencing is performed once in a lifetime

A re-analysis is not required, as the data can be reexamined by bioinformatic methods even years later in order to search for new data about the cause of the disease. This is due to the fact that publications with the identification of new diseases-associated genes are growing exponentially.

It is important that it is not always possible to find a «genetic cause» via whole exome sequencing. In this regard, in case of failure to obtain a result, the patient may be recommended genome sequencing.

Next generation sequencing (NGS): NGS — the term means the identification of the nucleotide sequence (the primary structure) of DNA or RNA. The technology allows to «read» several sections of the genome at once. The size of a each fragment read varies from 25 to 500 base pairs.
Genome: The genome is the totality of all hereditary material contained in the cell of an organism.
Clinical exome: The clinical exome is the totality of all exome genes whose clinical connection with diseases has been scientifically proven. It makes up about a quarter of the genes of the complete exome.
CMA molecular analysis: A molecular analysis of chromosomes using a genetic microarray (CMA — CHROMOSOMAL MICROARRAY ANALYSIS)), during which DNA is checked.
Monogenic diseases: Diseases whose etiology is based on a single gene mutation.
Panel sequencing: The study of coding regions of genes, that are mutated in specific groups of diseases (neurodegenerative diseases, connective tissue diseases, hereditary diseases of the gastrointestinal tract, eyes, kidneys, heart, etc.).
Proband: The patient in respect of whom exomic sequencing is performed in this case and a pedigree is compiled.
Genome sequencing: Determination of the entire DNA sequence, including non-coding regions. By this parameter, it differs from exome sequencing.
Cytogenetic test: Karyotype analysis, which allows to determine chromosomal changes in cells: the number and structure of chromosomes.
Exome: The part of the genome responsible for protein synthesis in the organism. The human exome corresponds to about 1% of the entire genome, or 30 million base pairs. An exome is a collection of all exons.
Exon: A district of a gene (DNA) carrying genetic information encoding the synthesis of a gene product (protein).