German program using whole genome sequencing to diagnose rare diseases and cancer risk

By Jane Byrne

- Last updated on GMT

© GettyImages/Gio_tto
© GettyImages/Gio_tto

Related tags Rare disease Cancer Diagnostics whole genome sequencing

A program at the University Hospital of Tübingen is the first in Germany to use whole genome sequencing (WGS) to improve the diagnosis of rare diseases and hereditary cancers.

The program is led by Professors Tobias Haack and Olaf Riess from the Institute of Medical Genetics and Applied Genomics. While they will use whole genomes to diagnose rare conditions, they will also use the information to generate scores for the risk of common diseases based on genomic data - polygenic risk scores. A polygenic risk score is a risk estimation of developing a disease based on the total number of genetic changes related to that disease. They say that this data will help identify individuals that may benefit from personalized healthcare management.

Spotlight on clinical utility of WGS

Illumina will support the new investigator-initiated study, called the Ge-Med Project, with sequencing, analysis, and health economic expertise. It sees the program as being very advanced in terms of the use of genomic data in disease prediction and prevention management.

It is leading within Europe,” ​Dr Sven Schaffer, head of scientific affairs, Illumina, told BioPharma Reporter.

“We know that WGS outperforms panel testing and whole exome sequencing in expert hands for research and diagnostic purposes. This has been shown in various meaningful studies worldwide and there are good data about it. Whether it enables a more accurate diagnosis in a routine clinical setting is a different question. There is currently limited research to inform practice about the broad clinical utility of first line genome sequencing across the different diseases and the implications for the hospital and the laboratory.

“Dr Riess and his team are bringing WGS to the patient in a real routine setting. While there are a few other projects dealing with the implementation of whole genome sequencing in the clinic – in Spain and in Sweden - the Tübingen program is the first one in Germany and one of the broadest in terms of patient profiling in Europe, with the team planning to enroll all patients with rare diseases as well as familial cancer cases.”

Sensitivity of WGS

Germany recently removed the prior authorization requirement for sequencing analysis by public health Insurers, meaning that the entire population now has better access to diagnostic approaches using whole genome testing, and programs such as this one in Tubingen will catapult the use of genomics in healthcare, said Illumina.

Previously, the Institute used whole exome sequencing for the diagnosis of rare disease conditions, which involves sequencing only around 1% of the genome known to contain the coding regions that provide instructions for making proteins.

The move to WGS is based on a two-year feasibility study by the Institute, supported by Illumina, which found that WGS provided improved diagnosis in the clinic in indications such as retina diseases - as many as 75% of genetic eye diseases were accurately diagnosed during the pilot project using WGS, including some forms of disease that could only be identified by sequencing the entire genome. 

It was also more effective in diagnosing rare childhood cancers and conditions that cause developmental delay in children.

“The success was such that we saw increased sensitivity of around 10% compared to whole exome sequencing, and we have, as a result, decided to switch completely to WGS for all indications now,”​ Professor Riess told us.

According to current estimates, in Germany alone, a rare disease directly affects about four million people. It is predicted that, in the majority of cases, the underlying cause is genetic in origin.  

Range of disease coverage

The team will be extending the use of WGS for diagnostic purposes as part of the Ge-Med Project to include indications such as neurological diseases, dystonia, ataxia and paraplegia, tissue connective diseases as well as cardiomyopathies, kidney, and rare liver diseases, said the project lead.

The program will not only be evaluating children but is being extended to adult patients as well.  

Indeed, Professor Riess said WGS will bring a lot of advantages in relation to the evaluation of hereditary cancer risk, another strand to this program at the Institute.

Familial breast cancer is generally associated with an early age of diagnosis and a higher frequency of disease among family members. Over the past two decades a number of genes have been identified that are unequivocally associated with breast cancer (BC) risk but there remain a significant proportion of families that cannot be accounted for by these specific genes. In fact, polygenic factors are thought to account for an additional 18% of the familial relative risk of breast cancer, with those at the highest level of polygenic risk distribution having a least a twofold increased risk of the disease. Hence the interest in providing a PRS for at-risk women with uninformative genetic test results.

Copy number variants (CNVs) are a form of genetic variation yet to be fully explored for their contribution to family BC, and WGS allows for detection of CNVs far more efficiently than any other enrichment protocols, said Professor Riess.

“We would like to implement polygenic risk scores in terms of genomic health implications [in Germany], in relation to breast cancer, diabetes and, eventually, cardiovascular diseases,” ​he said. 

Related topics Markets & Regulations

Related news

Show more

Follow us