Research could find new mutations associated with narcolepsy | AGÊNCIA FAPESP

Research could find new mutations associated with narcolepsy Presentation to workshop held by Brazilian Initiative on Precision Medicine (BIPMed) reinforces importance of sharing scientific data to identify genetic causes of diseases (photo: Felipe Maeda / Agência FAPESP)

Research could find new mutations associated with narcolepsy

December 19, 2018

By André Julião  |  Agência FAPESP – A group of researchers affiliated with the Federal University of São Paulo (UNIFESP) in Brazil has achieved what is probably the first whole-genome sequencing of DNA from “identical” (monozygotic) twins, one of whom has type 1 narcolepsy.

Narcolepsy is a neurological disorder that affects the sleep cycle, causing excessive daytime sleepiness and instability during deep or rapid eye movement (REM) sleep. Type 1 narcolepsy is characterized by cataplexy, a sudden involuntary loss of muscle function that can cause hazardous falls.

Patients with type 1 narcolepsy present with low levels of the neuropeptide hypocretin. Neither cataplexy nor a low level of hypocretin is present in type 2 narcolepsy.

The twins’ complete genomes were sequenced by a team led by Renata Carmona e Ferreira in collaboration with Fernando Morgadinho dos Santos Coelho, both of whom are professors in the Neurology Department of UNIFESP’s Medical School (Escola Paulista de Medicina, EPM), and by members of the Medical Genomics and Precision Medicine Laboratory led by Professor Marcelo Ribeiro da Silva Briones.

Preliminary findings of the research were presented during the 6th Workshop of the Brazilian Initiative on Precision Medicine (BIPMed), held on November 7, 2018, at the headquarters of FAPESP, which supports this initiative.

“Identical twins are great for studies of this kind of occurrence, as a large proportion of their DNA is identical, so the relatively small discordant part is potentially what leads to narcolepsy in one and not the other,” Ferreira told Agência FAPESP.


As soon as the research data are published, they will be made available via BIPMed, an initiative created in 2015 by five of the Research, Innovation and Dissemination Centers (RIDCs) funded by FAPESP. BIPMed is a database containing the genomes of healthy people and others with specific diseases. It is steadily growing and now contains genomes linked to epileptic encephalopathies, craniofacial anomalies, breast cancer, hereditary hearing loss, and neurofibromatosis. Sequences linked to lupus will be added in 2019.

More than 900,000 genetic variants are currently deposited in the database. The United States, Brazil and China are the countries that use it most.

“BIPMed aims to help implement precision medicine in Brazil, acting as a catalyst for collaboration among scientists, physicians, health authorities, hospitals and society,” said Iscia Lopes-Cendes, a professor at the University of Campinas’s Medical Science School (FCM-UNICAMP) and a member of BIPMed’s steering committee.

Another research project was presented by Briones, who studied the effect of variations in certain genes on drug metabolism. “In order to do precision medicine we have to know how the patient processes a drug in the body. Only then can we be sure of administering the right dose,” he said in his presentation.

The dose must be reduced if the patient is a poor metabolizer. In this case, it takes more time for the drug to be eliminated, and the drug can have toxic effects. On the other hand, a fast metabolizer needs a higher dose so that the body absorbs a sufficient amount of the drug to work as expected. These two groups each account for between 10% and 15% of the population. “If you think of Brazil, that’s about 20 million people, hardly a trivial number,” Briones said.


Large genetic databases provide clues to human evolution and adaptation in the Americas. Geneticist Tábita Hünemeier, a professor at the University of São Paulo’s Bioscience Institute (IB-USP), presented part of her research to the workshop; her research is funded by FAPESP and retraces the steps of the first Americans based on the genetic traits of their living descendants.

“Our results strongly suggest a signature of natural selection in all 53 Native American populations studied, including a strong signal in Amazonian populations that are extremely different from the Inuit with regard to culture, environment and diet,” she said in her presentation. The Inuit are indigenous people inhabiting the Arctic areas of Greenland, Canada and Alaska.

“In our opinion, this genetic profile suggests a single and very strong adaptive event that occurred in Beringia before the range expansion of the ancestors of the First Americans within the American continent and Greenland,” she added. Beringia, or the Bering Land Bridge, joined present-day Alaska to eastern Siberia at times during the ice age and is a postulated route of human migration to the Americas from Asia approximately 20,000 years ago.

“This event was linked to metabolic adaptations to diet and cold weather, which were constant during the Beringian standstill,” said Hünemeier, who was a member of the group that reinterpreted the history of the Lagoa Santa people (find out more at

Fátima Nunes, Full Professor at the University of São Paulo (USP), presented on sharing data across science databases in Brazil and worldwide as part of so-called Open Science (learn more at

For Victor Pylro, a professor at the Federal University of Lavras (Minas Gerais State) and coordinator of the Brazilian Microbiome Project, collaborative databases such as BIPMed facilitate networking by researchers and are fundamental to the advance of science.


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