Whole Exome Sequencing (WES) Guide: For Patients and Families

Your doctor or genetic counselor may have recommended that you or a family member have a test called Whole Exome Sequencing (WES). This guide has been prepared to help you learn more about WES. If you have questions about the information in this guide, please contact your doctor or genetic counselor.

Genetics

In all humans, almost every cell in our body contains about 20,000 genes; we inherit half of our genes from our mother and the other half from our father. Genes are the blueprints (or instructions) that control everything in our body, including our development, growth and health.

Our genes are made of DNA (deoxyribonucleic acid) and are organized into exons and introns. Exons are the coding regions of the gene; exons contain the information used to make the proteins needed for normal growth, development and organ function. Introns, on the other hand, are the non-coding regions of the gene and often contain important information about when during development (for example, in early pregnancy or in adulthood) and in which part of the body (for example, the heart or brain) a gene should be used.

All of our genetic information, including introns and exons, is called the genome. Exons make up a very small part (about 1-2%) of our total genetic information. The exons alone are called the exome.

Everyone's exome shows some differences compared with another person's exome – this is what makes us all unique! However, sometimes one or more genetic differences, genetic variants, can prevent one or more genes from working normally or cause them to work differently than expected. In these cases, these genetic variants lead to genetic diseases.

What is whole exome sequencing?

Most of the genetic variants that cause genetic diseases are found in the exome. WES is a test that examines the genetic information contained in our 20,000 genes (and their many exons) in a single test. WES cannot reliably detect non-coding regions and repeat expansions; a negative result does not rule out a genetic cause. This differs from other genetic tests in which only one gene (or a few genes) is examined at a time.

WES is performed using a special technology called next-generation sequencing (NGS). A DNA sample is collected from a blood or saliva sample taken from the patient. The patient's DNA is then compared with a reference sample (a sample representing the 'normal' sequence of human DNA) to look for any differences between the patient's DNA and the reference DNA. If there are differences, they are reviewed by specialist laboratory geneticists and specialist doctors.

Who should have WES?

WES can be performed during pregnancy, in childhood or in adulthood. During pregnancy, WES is performed with genetic counselling when a structural anomaly is present and karyotype/microarray does not provide a diagnosis. WES may reveal variants of uncertain significance (VUS) and secondary findings; which findings will be reported is chosen in the consent form before the test, and genetic counselling should be received before and after the test. It is usually performed for one or more of the following reasons:

1. A genetic condition is suspected in you (or your child)
2. Your symptoms (or your child's symptoms) may be caused by many different genes
3. You (or your child) have a complex medical history affecting many organs and/or body systems
4. You (or your child) have had genetic testing before but the results were normal

Who should not have WES?

WES may not be the ideal test if you or your child have a condition that is unlikely to be genetic, or a genetic condition that is known or likely to be caused by a single gene. Talk to your doctor or genetic counselor to find out which test is right for you or your child.

Why should you choose Eurofins Biomnis?

1. 20 years of specialized medical biology laboratory experience, Lyon, France
2. Test with ISO 15189 accreditation
3. Authorized to perform constitutional genetic tests
4. Certified clinical pathologists, geneticists
5. Mastery of sequencing techniques in diagnostic practice since 2014
6. The only laboratory providing a turnkey solution for WES at no additional cost
7. Lib Twist, Seq Illumina 2x150 Novaseq 6000. Perf: # 98% at 30x on Refseq + 2 pb, sensibility > 99% (perf checked on GiaB, on refseq target +/-20 pb with >15 Mo pairs reads, and 95% covereged > 10X ). Exome with accreditation ISO 15189, CE-IVD pipeline, data on secured HPD server.

Our WES Panels;

1. Extended oncogenetic panel including breast/ovary and prostate, digestive, pancreatic, kidney, skin, lung and neuroendocrine panels (75 genes): ACD, APC, ATM, BAP1, BMPR1A, BRCA1, BRCA2, CDH1, CDK4, CDKN2A, CDKN2B, CHEK2, DLST, DNMT3A, EGFR, EGLN1, EGLN2, EPAS1, EPCAM, ERBB2, FH, FLCN, GOT2, HNF1B, HOXB13, LZTR1, MAX, MC1R, MDH2, MEN1, MERTK, MET, MITF, MLH1, MSH2, MSH6, MUTYH, NBN, NF1, NF2, PALB2, PBRM1, PMS2, POLD1, POLE, POT1, PRKN, PTCH1, PTCH2, PTEN, RAD51B, RAD51C, RAD51D, RET, RTEL1, SDHA, SDHAF2, SDHB, SDHC, SDHD, SETD2, SLC25A11, SMAD4, SMARCB1, STK11, STN1, SUFU, TERF2IP, TERT, TMEM127, TP53, TSC1, TSC2, VHL, WT1.
2. WES (Whole Exome Sequencing)