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

All humans have approximately 20.000 genes in almost every cell in the body; 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 bodies, including our development, growth and health.

Our genes are made of DNA (deoxyribonucleic acid) and are organised into exons and introns. Exons are the coding regions of a gene; they contain the information used to make the proteins needed for normal growth, development and organ function. Introns are the non-coding regions of a gene and generally contain important information about when during development (for example, in early pregnancy or 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 proportion of our total genetic information (approximately 1-2%). The exons alone are called the exome.

Every person's exome differs in some ways from another person's exome – this is what makes us all unique! However, sometimes one or more genetic differences, known as genetic variants, can prevent one or more genes from functioning normally or cause them to function differently than expected. In these cases, these genetic variants cause genetic diseases.

What is whole exome sequencing?

Most 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 or repeat expansions; a negative result does not rule out a genetic cause. This differs from other genetic tests, which examine only one gene (or a few genes) at a time.

WES is performed using a specialised technology called next-generation sequencing (NGS). DNA is extracted 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 identify any differences between the patient's DNA and the reference DNA. If differences are found, they are reviewed by specialist laboratory geneticists and specialist doctors.

Who should have WES?

WES can be performed during pregnancy, childhood or adulthood. During pregnancy, WES is performed with genetic counselling when a structural anomaly is present and karyotyping/microarray testing has not provided a diagnosis. WES may identify variants of uncertain significance (VUS) and secondary findings; which findings will be reported is selected on the consent form before testing, and genetic counselling should be provided before and after testing. It is usually performed for one or more of the following reasons:

1. You (or your child) are suspected of having a genetic condition
2. Many different genes could cause your symptoms (or your child's symptoms)
3. You (or your child) have a complex medical history affecting multiple organs and/or body systems
4. You (or your child) have previously had genetic testing, 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 if you or your child have a genetic condition known or likely to be caused by a single gene. Talk to your doctor or genetic counsellor to find out which test is appropriate for you or your child.

Why choose Eurofins Biomnis?

1. Specialised medical biology laboratory with 20 years of experience, Lyon, France
2. ISO 15189-accredited testing
3. Authorised to perform constitutional genetic testing
4. Certified clinical pathologists and genetic specialists
5. Expertise in sequencing techniques for diagnostic applications since 2014
6. The only laboratory providing a turnkey solution for WES at no additional charge
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)

*Click here for general information about the WES test.

**Click here for information on why to choose Biomnis Laboratory for WES testing.