Study sheds light on paralysing nerve condition

British researchers have discovered a genetic mutation that causes a paralysing illness called ALS in some people, a finding they said on Thursday may lead to treatments for the degenerative nerve condition.

Their study showed how this genetic variation produced proteins that were toxic and killed motor neuron cells in people with amyotrophic lateral sclerosis or ALS, also commonly known as motor neuron disease or Lou Gehrig's disease.

"We discovered that the mutation was appearing only in people who were affected," said Chris Shaw, a researcher at the Institute of Psychiatry in London who led the study published in the journal Science. "This suggested it is disease-causing."

The finding is important, he said, because the disease kills quickly -- usually between two and five years after symptoms start -- and has no effective treatments. Physicist Stephen Hawking is a rare example of a person who has survived for years with the condition.

ALS leaves people unable to walk, talk or feed themselves but does not usually affect their intellect and other senses. Doctors diagnose about 120,000 new cases each year, according to the International Alliance of ALS.

Shaw and colleagues isolated a mutation in a gene called TARDBP in people with a rare, inherited form of ALS. They found that people with this variation produced a mutant and toxic protein called TDP-43.

Previous research had suggested the protein might have existed as sort of cellular junk generated as a harmless by-product of the disease. But by injecting these mutated proteins into the spines of chicks in eggs, Shaw's team showed they actually killed motor neurons.

While only about 1 percent of people have this form of ALS, the findings have wider implications because most people with the disease have these proteins accumulating in the wrong place within the cell, Shaw said.

"It also means we develop new and better disease models, which will bring us close to developing more effective therapies," he said.

In 1993 a group of U.S. researches identified a gene called SOD1 that caused a form of ALS affecting about 5 percent of people with the disease -- the only people with the condition who do not accumulate TDP-43 proteins, Shaw said.

That finding triggered a flood of new research into the disease, and the discovery of a second gene could draw even more people into the field, said Brian Dickie, director of Research Development at Britain's Motor Neuron Disease Association.

"The discovery of a new cause of the disease is of international importance, allowing researchers around the world to rapidly generate more pieces of the complex puzzle that is motor neuron disease," he said.

Gene studies confirm "out of Africa" theories

Two big genetic studies confirm theories that modern humans evolved in Africa and then migrated through Europe and Asia to reach the Pacific and Americas.

The two studies also show that Africans have the most diverse DNA, and the fewest potentially harmful genetic mutations.

One of the studies shows European-Americans have more small mutations, while the others show Native Americans, Polynesians and others who populated Australia and Oceania have more big genetic changes.

The studies, published in the journal Nature on Wednesday, paint a picture of a population of humans migrating off the African continent, and then shrinking at some point because of unknown adversity.

Later populations grew and spread from this smaller genetic pool of founder ancestors -- a phenomenon known as a bottleneck.

Populations that remained in Africa kept their genetic diversity -- something seen in many other studies.

"The one thing that I think we cannot say from this study is that any one person's genome is any healthier or evolutionarily fit than another person's genome," said Carlos Bustamante of Cornell University in New York, who worked on one study.

"You have to think of this at the population level," Bustamante said in a telephone interview.

Bustamante's team has been looking at the DNA sequences of 15 African-Americans and 20 European-Americans, examining tiny one-letter changes in the DNA code called single-nucleotide polymorphisms or SNPs (pronounced "snips").

FIT OR EXTINCT

They tested these changes to qualify them as benign, or potentially affecting genes, amino acids and eventually proteins in a way that could damage health or make people less "fit" -- in evolutionary terms, less likely to survive and reproduce.

"Like every other study ... the African-American panel as a whole showed more variation than the European-American panel," Bustamante said.

Then his team did a computer simulation of a bottleneck, and found it predicted this pattern.

Bustamante said it is possible some of the SNPs are beneficial, and he said his team and others should compare the genetic changes they found to known genetic changes linked with diseases.

"I wish we had done that (already)," he admitted.

In the other study, Noah Rosenberg and colleagues at the University of Michigan and the National Institute on Aging analyzed DNA from 485 people around the world.

They looked for three types of genetic variation, including SNPs and larger changes that involve duplications, deletions and repetitions of large segments of DNA.

The patterns they found produced what they call the highest-resolution map yet of human genetic variation.

They also reinforce the idea that humans originated in Africa, then spread into the Middle East, followed by Europe and Asia, the Pacific Islands and finally to the Americas.

"Diversity has been eroded through the migration process," Rosenberg said in a statement.

People of African descent are the most genetically diverse, followed by people from the Middle East, and then Asians and Europeans. Native Americans resemble one another the most on a DNA level.

The study also found it is sometimes possible to trace a person's ancestry to a small group within a geographic region.