Analyzing the ancient origins of rare genetic diseases

It's another busy day for Dr. Atil Bisgin at the Çukurova University hospital in Adana, Turkey. Despite the high pressure of his work, his calm composure is reassuring as he stands near the entrance of the hospital, where his life’s work is stored and lies cooling: A cache of over 50,000 samples spanning the Eurasian continent from patients afflicted with rare genetic diseases. Today, over 8,000 rare diseases affect the world population and still lack effective treatment. Most rare diseases are of genetic origin and are very severe – even life threatening – and remain undiagnosed in the critical stages.

The intrinsic challenges facing the medical community are a general lack of knowledge of diagnosing and treating rare diseases due to a multitude of factors, including limited reported patients and the technological capacity to analyse large amounts of data. This in turn leads to patients receiving an extremely delayed diagnosis since technologies and processes remain at a bottleneck.

Located in the south of Turkey, the ancient city of Adana is a picturesque hub only a few kilometers away from the Syrian border, where civilizations such as the Phoenicians, Assyrians, Persians, Macedonians, Romans, Byzantines Seljuks and the Ottoman Empire once ruled. The region’s rich cultural heritage has been profoundly influenced by its role as a former station along the Anatolian-Arabian trade routes, a factor which significantly effects Bisgin’s work today. “Adana’s unique location has greatly influenced the population living here for centuries and impacts our current work in the clinic,” says Bisgin. “For thousands of years, it’s been a place where European and Middle Eastern cultures have interacted. From a genetic point of view, it's very exciting,” he says.

For example the types of cancer found in the region’s citizens often show a wide variety of mutations rarely found elsewhere. Many samples from the university hospital in Adana come from patients in Iraq or Syria, which lack a cohesive medical infrastructure due to the region’s many conflicts. According to Bisgin, this group shows a completely different genetic picture than that in multicultural Turkey. “Particularly in remote areas,” he says, “parts of the population show only minor genetic variance, which is why the inhabitants are more frequently affected by hereditary diseases, sometimes even by several at once.” Samples from such patients are added every day, benefiting not only the patients when their data is interpreted, but also enriching the database.

Turkey is now considered one of the largest markets for sequencing technology, and as the largest laboratory in the region, Bisgin's team processes all samples from the university hospital, as well as those from other nearby hospitals and institutes. They are even supplied with samples from other European countries, clinics and research institutions via FedEx. Due to the quantity of data being processed, Bisgin’s laboratory is challenged with analyzing a large number of very rare cases, as well as recommending the most promising therapeutic approaches.

To keep up with the demand, Bisgin's laboratory is filled with state-of-the-art equipment, including PCR and next-generation sequencing systems, that run around the clock. Many of these samples contain rare mutations or are from patients with hereditary diseases that require individual investigative work. In the past, analyzing such an extensive range of complex biological data would have been out of the question, but QIAGEN Digital Insights solutions provide the tools to handle large-scale data to identify genetic mutations and sequences, to help diagnose disease.

QIAGEN’s systems allow him to create his workflows, regardless of the number of samples. The quality of the panels also helps; with 64 genes, the spectrum is broad. Using liquid biopsy, Bisgin can examine all kinds of samples for DNA and RNA. However, the most important part for him is not the equipment, but the bioinformatics tools. “Anyone who, like us, processes tens of thousands of samples per year can only do this with effective computer science. QIAGEN offers valuable solutions that enable us to easily manage our raw data. One of the major advantages for me is to be able to access our data at any time, and from any place, even in the plane,” says Bisgin.

Bisgin uses QIAGEN Ingenuity Variant Analysis and QIAGEN Clinical Insights to conduct his work on finding cures for rare disease with the help of applications like Analysis Universal and Interpret. “I can access thousands of patient data simultaneously and correlate them with additional data sets through access to global platforms,” he says. “For example, we can compare results with the Mediterranean panel for breast cancer, search for comparable mutations and infer resistance to certain therapies,” he explains. Bisgin considers this access to worldwide databases – and the massive number of references – to be exceedingly important. “We could never build up that amount of data ourselves, so we depend on this global data from QIAGEN´s bioinformatics,” he says.

Bisgin adds that while he often trusts his gut feeling when it comes to patients, he always verifies his hunches by using bioinformatics tools. The tools also enable him to collaborate with bioinformatics experts in both Europe and the US via QIAGEN's expert boards to create the most thorough workflows and results. “It provides a way to produce better statements for doctors, such as whether surgery might be preferable to chemotherapy for a particular patient,” he says.

To Bisgin, uncovering a cure for rare diseases is more than a job, it’s his dedicated passion, one he shares with his team. “Sometimes we work until midnight,” he admits, “as some deadlines simply can’t be pushed back. But I don't want to burn them out either.” To promote both a balance at work and help build empathy for their patients, Bisgin organizes a monthly movie night at the lab for all the employees. The movies they watch are related to their work in some way and put the entire picture of disease into perspective. Diseases are extremely stressful on the patients and their families – the movies depict real life scenarios and help provide a better understanding of what the patients and their families go through when disease strikes. “Everyone here should know who we work for and why our work is so important,” says Bisgin.