Gene duplications associated with autism evolved recently in human history

October 19, 2014

Human geneticists have discovered that a region of the genome associated with autism contains genetic variation that evolved in the last 250,000 years, after the divergence of humans from ancient hominids, and likely plays an important role in disease. Their findings were presented today at the American Society of Human Genetics (ASHG) 2014 Annual Meeting in San Diego.

Researchers at the University of Washington analyzed the genomes of 2,551 humans, 86 apes, one Neanderthal, and one Denisovan. They closely examined a region of human chromosome 16 known as 16p11.2, a region prone to genetic changes in which segments of DNA are deleted or duplicated, one of the most common genetic causes of autism, schizophrenia, and other conditions. The geneticists found that certain segments of DNA in this region are repeated a variable number of times in different people and may also be associated with disease.

To trace the origins of this variation, the researchers collaborated with colleagues at the University of Lausanne and the University of Bari to sequence and analyze corresponding regions of ape genomes.

"When we compared the genomes of apes and humans, we found that the humans had evolved complex structural changes at 16p11.2 associated with deletions and duplications that often result in autism. The findings suggest that these changes emerged relatively recently and are unique to humans," explained study author Xander Nuttle, BS, BSE, a graduate student in the Department of Genome Sciences at the University of Washington School of Medicine.

While this has likely made humans more vulnerable to disease, the scientists believe it also contributed to the formation of novel genes. One such gene is BOLA2, a gene thought to be important in cell reproduction. The researchers found that while apes, Neanderthals, and Denisovans had only two copies of BOLA2, all have between three and 14 copies, with an average of six. The team is currently studying the function of BOLA2 to understand the potential significance of additional copies for evolution.

"Another question we are exploring is why people with the same duplications and deletions at 16p11.2 vary in disease severity," Mr. Nuttle said. "Some people are healthy or have mild illness, while others are severely affected and have multiple clinical diagnoses."

One hypothesis is that differences among people in how the region is organized, such as the number of copies of genes like BOLA2 present and the precise locations at which deletions and duplications start and end, contribute to this variability. To examine this possibility, Mr. Nuttle and colleagues are analyzing DNA and medical data from over 125 individuals with deletions or duplications at 16p11.2.

"We believe this work will lead to new insights about the genetic underpinnings of autism and other conditions associated with 16p11.2 deletions and duplications, potentially paving the way for more specific diagnostics and treatments for patients in the future," Mr. Nuttle said.

Explore further: New evidence for genetic basis of autism found

More information: abstracts.ashg.org/cgi-bin/2014/showdetail.pl?absno=140122421

Related Stories

New evidence for genetic basis of autism found

October 3, 2011

Scientists at Cold Spring Harbor Laboratory (CSHL) have discovered that one of the most common genetic alterations in autism -- deletion of a 27-gene cluster on chromosome 16 -- causes autism-like features. By generating ...

Recommended for you

3 comments

Adjust slider to filter visible comments by rank

Display comments: newest first

JVK
1 / 5 (4) Oct 19, 2014
Gene duplication is nutrient dependent and the metabolism of nutrients to species-specific pheromones controls the fixation of amino acid substitutions that differentiate all cell types in all individuals of all species.

Evidence that 500 different species of fish arose in 15,000 years challenges the ridiculous assumptions of population geneticists who have insisted that millions of years (or hundreds of millions) are required for accumulated mutations to somehow lead to increasing organismal complexity. No biologically-based experimental evidence supports those assumptions.

What should we assume supports that claim "...that a region of the genome associated with autism contains genetic variation that evolved in the last 250,000 years, after the divergence of humans from ancient hominids, and likely plays an important role in disease."?
alfie_null
5 / 5 (1) Oct 20, 2014
. . . challenges the ridiculous assumptions of population geneticists . . .

If you want traction, go publish something. Pushing your views to an audience of laypeople is ridiculously dishonest.
JVK
1 / 5 (3) Oct 20, 2014
Thanks for the suggestion. This was published last year and has been viewed 9400 times since tracking began in January 2014.

http://www.ncbi.n...24693353

It follows from a history of published works that extend back to book publication in 1995, and included two award-winning published works.

Why should only the lay audience remain ignorant about the invention of neo-Darwinism and definitions with assumptions?

"[W]hat Haldane, Fisher, Sewell Wright, Hardy, Weinberg et al. did was invent.... The anglophone tradition was taught. I was taught, and so were my contemporaries, and so were the younger scientists. Evolution was defined as "changes in gene frequencies in natural populations." The accumulation of genetic mutations was touted to be enough to change one species to another.... No, it wasn't dishonesty. I think it was wish fulfillment and social momentum. Assumptions, made but not verified, were taught as fact."

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.