An international team of researchers has finished a comprehensive study aiming to identify novel, medically interesting, rare genetic variants. For this, they utilized a special isolated population, Finns. The findings, published online in PLOS Genetics today June 31st, show that compared to other studied nationalities, an average Finn has almost twice as many deleterious gene variants that completely destroy the function of the gene in question.
The researchers were especially interested in such deleterious variants that are more common in Finland than elsewhere. They studied the presence of more than 80 such variants in 36,000 Finns. Some of the studied genetic variants are mutations that cause severe diseases when inherited from both parents.
“But even more interesting are the genes that we can live without,” said the co-director of the multinational research team, Professor Aarno Palotie from the Institute for Molecular Medicine Finland (FIMM), University of Helsinki and the Broad Institute of MIT and Harvard. “We identified several genes that do not cause any health problems to the individuals completely lacking them. Surprisingly, it seems that lacking some genes might even be protective from certain disorders, such as cardiovascular disease.”
For the researchers, these individuals can be regarded as interesting experiments of nature. However, to be able to make definite conclusions about the neutral or even beneficial effect of lacking a complete gene product, researchers often need to utilize special populations.
“Finland is a great example. There are several advantages for performing genetic studies in a country like this. The population history of Finns has led to a situation where some of these rare variants we are interested in are not that rare. Almost as importantly, Finnish research institutions have a long history of collecting large population cohorts with systematic and detailed health related information. Thus it is possible to identify several hundreds of people lacking a certain gene and immediately see whether they are sick or healthy or anyhow exceptional,” said Professor Mark Daly from Broad Institute of MIT and Harvard, the co-director of the study.
Using this strategy, the team showed that individuals completely lacking a LPA-gene that codes for a blood lipoprotein had a significantly lowered risk of coronary heart disease.
“Genes whose absence is beneficial for the individual are exceptionally interesting drug targets. Traditionally, researchers have used animal models to determine what kind of health effects lacking a gene causes. Human “knockouts” provide a shortcut. New drugs developed to lower or block these gene products will very likely be safe since there are individuals who have been living healthy lives tens of years without these genes.”
“To me this is a proof of concept - first study showing that Finnish population is valuable in identifying protective gene variants. I’m certain that many more findings will follow,” Aarno Palotie concluded.
Lim, Würtz, Havulinna, Palta, Tukiainen, Rehnström et al. Discovery of medically important loss-of-function variants in the Finnish population. PLOS Genetics. Online 31.7.2014.
Professor Aarno Palotie
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