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Bad Genes

STUDY SHOWS SURGE OF BAD DISEASE GENES IN EUROPEANS…By Maggie Fox, Senior Writer, NBC NewsA scan of all the mutations in the human gene map shows something surprising – people of European descent are evolving fast, and not for the better.The study finds that in the past 5,000 years, European-Americans have developed a huge batch of potentially harmful genetic mutations – many more than African-Americans.

The study, published in the journal Nature, may help explain why so many people develop diseases even though they don’t have common genetic mutations. It can also help explain why different people have so many different reactions to the same drug, said Joshua Akey of the University of Washington in Seattle who led the study.

It likely has to do with population explosion, Akey said. European populations expanded after the Ice Age ended and prosperous agricultural societies emerged. “The number of mutations that exist is directly attributable to the population growth that happened in the last 5,000 years,” Akey told NBC News.

“The things that allowed us to go from millions to billions of has also been the same process that has been pumping in all these new mutations.”Akey and colleagues at genetics institutions across the country examined the gene sequences of more than 6,500 people – more than 4,200 European-Americans and 2,200 African-Americans.

They were looking for small changes in the genetic code called single nucleotide variants – one-letter differences in the genetic code of A,C, T and G.They found “an enormous excess of rare variants” in the European-Americans. And 73 percent of these mutations only appeared in the human genome in the past 5,000 to 10,000 years. Most were mutations that are known to weaken proteins, Akey said, and most of these harmful mutations were also in the people of European descent.

Now researchers are working to see which of these mutations might be associated with diseases. But many are in known disease-causing genes, such as the LAMC1 gene associated with premature ovarian failure, LRP1, which is linked with both Alzheimer’s disease and obesity and the CPE gene linked to hardening of the arteries.Most are rare mutations – meaning they only affect a few people.

“Some genes might be more disease-causing than other genes,” Akey said.It may explain why it’s been so hard to find clear genetic links to many diseases. “We have been looking for disease risk where it isn’t,’ he said. “The last five to 10 years have been dominated by looking for common genetic variations that dominate common diseases. There is a lot of disease risk that is unexplained. Maybe there are classes of mutations that haven’t been looked at.

”The findings could explain why some people can smoke for a lifetime and never get lung cancer or heart disease, while someone else might suffer a heart attack despite having healthy blood pressure and cholesterol levels.It definitely shows evolution in action, Akey said. “It’s just the process of evolution playing out in real time,” he said. “The dramatic population expansions that occurred over the past couple thousand years had a profound consequence on our genetic variability.

”Genetic mutations usually occur by accident – they are just mistakes that get made when DNA gets copied. They become important to evolution when they affect a person’s ability to survive and have children. The expansion of civilization, and the ability of societies to care for people who are less fit, was probably a factor in allowing these mutations to spring up, Akey said. “I think that is undoubtedly true,” he said.Some of the genes identified in the scan also affect peoples’ response to drugs.

That could explain why some people are helped, for example, by a cholesterol-lowering drug while others may not be. There wouldn’t have been much “selective pressure” on these genes before the modern drug era, but that doesn’t mean the genes were not influenced by something else. “It turns out that genes involved in adverse drug responses also have different biological roles,” Akey said – for instance, detoxifying certain foods.There may even be more evolution in the future, Akey predicted. One example – phenylketonuria or PKU.

It’s caused by a mutation in a gene that breaks down an amino acid called phenylalanine. People with PKU mutations must eat a strict, low-protein diet or they can develop seizures and mental retardation.Now newborns are routinely tested for PKU so they can start the diet immediately and avoid any brain damage. Akey said because these kids can now grow up and lead normal lives, they will likely start having children and the gene may become more common in the population

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