What Is Whole Genome Sequencing? What Is It For

Whole Genome Sequencing is a powerful tool that allows us to deeply analyze our genetic code. This technique helps us accurately detect any genetic alteration that could directly impact our quality of life. Its primary use is in the diagnosis of genetic conditions, including inherited diseases and genetic syndromes.

What is the full Whole Genome Sequencing for?

About 85% of human genetic diseases or conditions are related to changes in the DNA sequence, which modify the structure of the proteins that constitute the correct functioning of our metabolism. These changes often cause syndromes, a set of metabolic characteristics that somehow affect the correct performance of our body. Due to their multisystemic nature, these syndromes share many similarities, so giving an accurate diagnosis only from a clinical approach is complicated.

Whole Genome Sequencing allows us to detect promptly which genetic alterations are present and, in this way, give them the most appropriate diagnosis and treatment.

Whole Genome Sequencing as a rapid and inexpensive diagnostic test

Thanks to a new study, researchers have found that Whole Genome Sequencing offers a reliable, fast, and inexpensive diagnosis of heterogeneous diseases.  

Scientists found that the exome-based test outperforms the widespread Sanger sequencing method. Deoxyribonucleic acid (DNA) is used as a template to obtain a set of fragments whose length varies by a single base. These fragments are then separated by size, and then the bases at the ends are identified so that the original DNA sequence is recreated. The main advantages of Whole Genome Sequencing are that it is fast and inexpensive.

According to the fundamental genomic analysis of the department of the genetics, collaborators examined genome sequences of 262 patients suffering from 6 different heterogeneous diseases: intellectual disability, blindness, deafness, motor disorders, cancer and oxidative phosphorylation (Oxphos). Five hundred genomesequences were analyzed in the study. In cases of intellectual disability, the genomes of the father, mother, and child were evaluated, while for other diseases, only the data of the patient’s genome were filtered.

The odds of finding a causal mutation in a single gene are low. But they are high in a pool of more than 100 genes, as shown by results for patients. Thanks to Whole Genome Sequencing, up to twenty thousand genes can be analyzed with a single generic test. Because of its high throughput and lower costs, more can be analyzed with less money. But before applying the test on a larger scale in our laboratory, we had to make sure that it would give us reliable diagnostic results.

What are Exons DNA sequences

Exons are short DNA sequences that represent the regions of genes that are translated into proteins. The human genome contains about 180,000 exons, which make up about 1% of it. According to experts in the field, the regions of the exons contain around 85% of all the mutations responsible for diseases. However, the Whole Genome Sequencing only allows identifying the conditions when they affect the function of the proteins.The method covers 500 base pairs per analysis, while the most innovative sequencing techniques allow examining millions of sequencing reactions per analysis.

Before there were no guidelines for Whole Genome Sequencing, it was created with diagnostic workflows, measures and standards. What criteria did we have to set before we could announce the result? What kind of informed consent was necessary? How could we organize the confirmation of our results? These were all questions that needed to be answered and we engaged in discussions with numerous clinical geneticists, researchers and ethicists before we got down to business.

Apart from the observations in intellectual disability and blindness cases, they confirmed causal relationships of mutations in about 20% of cases of deafness, in between 15% and 20% of cases of motor disorders, and about 25 % of Oxphos cases. Although in many cases it is not possible to treat their diseases, it should be borne in mind that most of these patients have to travel a long and worrying path through different practices and hospitals until they receive a diagnosis.

Why use Whole Genome Sequencing

Whole Genome Sequencing can shorten this process and also simplify the work of clinical staff by not having to decide which specific gene to analyze, a very complicated decision as there are a hundred or more genes involved in each disease. In Whole Genome Sequencing techniques, all causative genetic mutations are examined at the same time, allowing an accurate diagnosis to be made quickly. Even if there is no specific treatment, the mere fact of having a diagnosis can help parents, patients, and healthcare professionals to make informed decisions regarding treatment and care and also to plan their future. Genetic diagnosis is only gaining importance in the clinical setting, and we believe that, as it develops, the genome-based technique will be one of the first to be considered by a physician when they suspect a particular condition.