Starting in this month's newsletter we will be taking a closer look at the various team members that comprise the University of Chicago Genetic Services.  First up is Soma Das, Ph.D., Professor and Director of the DNA Diagnostic laboratory.  Dr. Das received her B.Sc. in Health Sciences from the University of Ife, Nigeria, followed by her M.Sc. in Medical Genetics from the University of Glasgow, and her Ph.D. in Biology from the University College London, UK.  Following a post-doctoral fellowship at the University of California, San Francisco, she completed her clinical molecular genetics fellowship at UCSF.  Dr. Das has been the director of the DNA diagnostic laboratory at the University of Chicago since 1996.

CT: Can you tell us more about your particular scholastic interests that led you to the field of Human/Molecular Genetics? 

SD: My interest in the field of human/molecular genetics actually started in my undergraduate days.  I was doing an undergraduate degree at the University of Ife, Nigeria, as part of medical school and did a thesis study in the genetics of hemoglobinopathies.  This got me interested in genetics and wanting to do more laboratory-based work.  I quit medical school and joined a masters program in medical genetics at the University of Glasgow and then went on to do my Ph.D. at the University College London.  The laboratory that I did my Ph.D. thesis work in was part of the Imperial Cancer Research Fund and I worked in the laboratory of Dr. Bryan Young at St. Bartholomew’s Hospital in London.  My thesis work was on the molecular characterization of the 11q23 translocation breakpoint in patients with leukemia and this continued to build on my interest in the field of human molecular genetics. I was then lucky enough to get a postdoctoral position with Dr. Jane Gitschier at the University of California San Francisco where I worked on mutation identification in patients with Menkes disease at the time the ATP7A gene was discovered in her lab.  It was at this time that I learned about the fellowship-training program in clinical molecular genetics and joined the program at UCSF.  This was actually perfect for me as it combined my clinical interests (my initial start in medical school) and interest in human/molecular genetics. 

CT: You have been Director of the Molecular Diagnostic Laboratory at the University of Chicago since 1996.  Can you tell us about those early days?  Did you come into this position with any specific vision or goals for the lab?

SD: During my clinical molecular genetics fellowship training, I was doing work on Menkes disease in Jane Gitschier’s research laboratory.  The gene for the disorder had just been identified and we were identifying mutations in patients enrolled in our research study.  This led to the question about how best to help such families who were now interested in carrier testing and prenatal testing options.  We looked around and approached molecular diagnostic laboratories about setting up testing for Menkes disease as the gene had now been identified.  However this was not something that clinical labs were set up to do at that time – the gene was large and there were no common mutations. How would results of novel changes be interpreted? How could the lab validate the test or do proficiency testing? In addition, it was a very rare condition and genetic testing would likely be costly.  This raised the question in my mind of how best to translate research findings of rare orphan genetic disorders (like Menkes disease) to the diagnostic arena.  When I came to the University of Chicago this was what I wanted to do.  I wanted to set up a lab that would focus on the diagnostics of rare orphan genetic diseases.  Such labs did not exist at that time and I reasoned that even though these were rare conditions, there were hundreds of these rare conditions and combined would result in a lot of patients/families for whom such testing would be beneficial. This necessitated the development of an infrastructure and guidelines by which to do testing for such disorders where patients were likely to have their own novel and private mutations.

CT: The field of molecular diagnostic testing has moved forward at a very rapid pace.  How have the lab and the field of molecular diagnostic testing changed over the last 17 years? 

SD: So much has changed in these past 17 years.  When I started the lab, DNA sequencing as a diagnostic tool was a novelty.  Testing was performed for specific mutations with a clear establishment to disease.  Sequencing genes to look for new mutations raised questions as to how to interpret novel changes and their implication to disease.  Gene sequencing is now the standard in diagnostic testing and I feel privileged to have been part of the development of this process.  Over the years the laboratory has developed single gene and gene panel sequencing for a wide range of orphan genetic conditions in addition to performing exon-level array CGH for the detection of intragenic deletions/duplications in these genes to enable comprehensive mutation analysis for these disorders.  The development of new high throughput technologies has had a tremendous impact on the field of molecular diagnostics and has been the main contributor to the rapid pace of the changes in molecular diagnostics.   Entire exomes are now being sequenced in some diagnostic labs!  We need to take advantage of these new technologies to allow the development of more comprehensive and more cost-effective diagnostic testing.  However, we need to do this in a responsible manner.

CT: What do you think is the greatest challenge facing molecular diagnostic testing now and in the near future?

SD: One of the greatest challenges facing molecular diagnostics now is how best to use the deluge of data that can now be generated by whole genome and exome sequencing of patient samples.  Where should the line be drawn as to what results should be returned back to patients from such studies?  We also have a lot to learn about what all the results mean and we need to have a better understanding of how to interpret such findings in order to help our patients in the most responsible and best possible way.