Broken genome can be the cause of a broken mind, shows Olli Pietiläinen
Schizophrenia is a highly heritable and relatively common mental disorder, 1-2% of the population being diagnosed of having this disease. The main aim of Olli Pietiläinen’s thesis, was to study the role of large chromosomal copy number variants in schizophrenia.

In his thesis, M.Sc. Olli Pietiläinen was able to show that a small proportion of the genetic risk of schizophrenia is due to rare, large chromosomal deletions. The identified deletions overlapped several genes that have a role in neuronal development. Furthermore, the phenotypic spectrum of the symptoms associated with these deletions was shown to vary from mental disorders to learning difficulties. The genetic findings together suggest that schizophrenia is as biological as any other somatic disorder and that it can be regarded to be one form of neurodevelopmental disorder.

– The genetic findings support the theory that part of the biological etiology for different psychiatric disorders is shared. This challenges the current categorized clinical view, said Olli, who is a PhD student at FIMM and at Hjelt Institute (University of Helsinki) and also affiliated with the National Institute for Health and Welfare.

His thesis, entitled “Rare Genomic Deletions Underlying Schizophrenia and Related Neurodevelopmental Disorders”, was supervised by prof. Aarno Palotie, prof. Jaana Suvisaari and the late Academician of Science Leena Palotie.

Olli has an interesting and a somewhat unusual background for a medical geneticist. He has studied chemistry as his major subject which led to a situation where a little bit creativity was needed to find a suitable Master’s thesis topic.

Olli entered his research career almost immediately after starting his university studies. In 2004, he worked as a summer student in Leena Palotie’s psychiatric disease laboratory. He was very inspired by the topic, fellow students and, naturally, Leena Palotie herself. Thus the decision was easy – he wanted to continue with this project. This path has led him from KTL (National Public Health Institute) to FIMM and to Sanger Institute where he spent a couple of years.

– To me, clearly the most important finding of this thesis work is the topoisomerase III beta (TOP3B) gene deletion that was published in Nature Neuroscience last summer. Actually, I identified the deletion already several years ago. At that point we didn’t, however, have enough proof to show that the deletion is truly associated with the schizophrenia phenotype, said Olli.

– Furthermore, the field is much more responsive now than a couple of years ago for this kind of results due to the “new rise” of rare, high impact variants behind complex diseases. The publication is a nice example of the importance of international visibility and collaboration and the value of the well phenotyped Finnish cohorts. The German researchers who performed the functional studies stumbled into our online abstract. With their help we were able to report the interesting biochemical roles of this particular topoisomerase.

Since early childhood it has been clear to Olli that he wants to be a scientist. When one of his relatives got a stroke and was paralyzed, young Olli announced that when he grows up, he wants to find a way to get people to walk again.

– For me, being a scientist means that it is possible to find something completely new that, in the best case, will eventually benefit patients. It is also important for me that in this job I can utilize a broad range of skills. For example, I enjoy ranting about genes and how they function. Being a Finn studying genetics in Finnish population has of course its own thrill to it. We are genetically very fascinating population with our own peculiar genetic makeup. The genetic structure of Finns was also crucial in identifying the TOP3B deletion described in my thesis.

Olli will continue his scientific career as a Postdoctoral Researcher at the Harvard Stem Cell Institute, in the group of Kevin Eggan. He wants to dig into the biological mechanisms behind psychiatric disease more deeply.

– Since brains are composed of so many different cell types it is not straightforward to select the correct target cell type for functional studies. This will be an interesting challenge, but hey, I like challenges!

The public examination of M.Sc. Olli Pietiläinen's doctoral dissertation, "Rare Genomic Deletions Underlying Schizophrenia and Related Neurodevelopmental Disorders" will take place on 19 December at 1 pm in the Lecture Hall 2, Haartman Institute (Haartmaninkatu 3). His opponent is Professor Cathryn Lewis (King's College London) is the opponent and Professor Samuli Ripatti the Custos. 

The dissertation is available in electronic form through the E-thesis service