Despite Evolution, Genetic Diseases Persist Interview with:

Carlos Eduardo G. Amorim PhD Columbia University Department of Systems Biology Irving Cancer Research Center

Dr. Amorim

Carlos Eduardo G. Amorim PhD
Columbia University Department of Systems Biology
Irving Cancer Research Center What is the background for this study?

Response: More generally, we were interested in understanding the determinants of the frequencies of mutations that cause disease in humans.

More specially, we wanted to test if a long-standing theory in population genetics (namely mutation-selection balance) was a good explanation for the observed frequencies of disease mutations in humans. What are the main findings?

Response:  We find that the frequencies of disease mutations can be explained by a balance between their rate of introduction (by replication errors or DNA damage) and the rate that they are purged by natural selection (i.e. When the carrier dies because of the disease).

We also described the effect of other factors (besides rate of introduction and natural selection) on the frequencies of disease mutations. e.g. Demography, gene interactions, relaxation of natural selection etc.

Finally, we also show that the medical literature on Mendelian (monogenic) diseases is biased towards mutations that are segregating in high frequency. That means that there are many disease mutations to be discovered, but they are segregating in low frequencies (making it difficult for us to find them). What should clinicians and patients take away from your report?

Response: I like to think that this paper bridges population genetics to medical genetics. I hope our work may be useful for researches in the future to design more efficient strategies to find disease mutations.

We also show the power the new massive datasets in human genetics have to elucidate mechanisms of medical importance and to test theories in population genetics. And one last thing: we show that the mutation-selection balance model applies to humans. This theory has been used since decades, but was never formally tested. What recommendations do you have for future research as a result of this study?

Response: Maybe that one should be aware that disease mutations sometimes are more prevalent than what we’d expect them to be. Is there anything else you would like to add?

Response: Some questions are still not answered and I’d like to answer them in the future. One is why some genes harbor more detrimental mutations than others? Another one is: why some individuals are able to tolerate fatal mutations and others not? Thank you for your contribution to the community.


The population genetics of human disease: The case of recessive, lethal mutations

Carlos Eduardo G. Amorim ,Ziyue Gao,Zachary Baker,José Francisco Diesel,Yuval B. Simons,Imran S. Haque,Joseph Pickrell ,Molly Przeworski

  • PLOS Genetics Published: September 28, 2017

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.







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