The Magnificent World of Genetics Interactions

ONLINE POST in ENGLISH, commissioned | AMP Student 2016;18

As I began my research in Genetics, I realized this is a beautiful field, full of complexity but with a lot of marvelous interactions. As Medical students, I think it is crucial for the future clinicians to acquire knowledge in Human and Basic Genetics. Genetics is the basis of everything (afterwards, the environment changes us, starting from the intrauterine environment, our behaviors and life styles throughout life modify our genetic background but Genetics is the raw material that we are made of).

I observed during these years that in order to go into the Genetics core we need to contact with a lot of scientists in different areas, with different medical specialists and several other professionals.

Besides Human Genetics, I devoted myself to
the study of Statistical Genetics, which can be very awkward for some people but in fact the design and the analysis of the research projects is paramount to take conclusions in Biomedical Sciences studies.

dna-163466_1280Statistics is not the awful tool, a kind of torture that most of the students think when they first contact with this discipline. In fact, it is challenging and obliges us to be attentive, to be demanding with our patients’ sample, with the clinical diagnostic that it is performed, with all the confounding bias that can
affect conclusions and that can be crucial for the development of new therapeutic strategies

As an example of the essential interactions that arise within a genetic study, the current focus of our research group is Familial Amyloid Polyneuropathy (FAP), an autosomal dominant systemic amyloidosis, described by Professor Corino de Andrade in Portugal in 1952. It is due to a point mutation in the transthyretin (TTR) gene and more than 100 mutations have been found in the TTR gene. The V30M is the most common mutation found in the Portuguese patients but although they carry the same mutation, they present a wide variability in age-at-onset which shows that other genetic or epigenetic factors may be present, modifying disease’s onset. This can have important clinical implications in genetic counselling of offspring and in follow-up of mutation carriers. Therefore, our team involves specialists in neurology and amyloidosis, clinical genetics, applied mathematics, statistical genetics, genetic epidemiology and molecular biology. Our group was able to show in 2014 (Lemos et al, JNNP, 2014) that anticipation of age-at-onset is a true biological phenomenon by using precise statistical and epidemiology tools, combined with an accurate clinical diagnostic performed by the team of neurologists. Another example is the clinical evaluation of one- and two-year treatment at Unidade Corino de Andrade, CHP, of FAP patients with Tafamidis, the drug that has been shown to stabilize TTR and prevent amyloid deposition (Coelho et al, Orphanet J Rare Dis, 2015). Within this study, several analytical tools were used and statistical approaches in order to evaluate Tafamidis efficacy and safety, concluding that Tafamidis stabilized 69% of patients treated for one year and 57% of patients treated for two years.

Also, one of our PhD students is currently in the United States studying an animal model (C.elegans), in order to find genes that can be modifiers of FAP phenotype and that can recapitulate the phenotype in patients. Another PhD student is analyzing variants in candidate-genes using DNA samples from patients and published recently a paper describing her first results (Santos et al, EJHG, 2015).

Therefore, from my personal experience to have the opportunity to show you, medical students, a little bit of the wonderful world of genetics and to motivate you for medical research is a challenge that I hope all of you are ready to take!

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