DNA 'bias' may keep some diseases in circulation, biologists show

It's an early lesson in genetics: we get half our DNA from Mom, half from Dad.

But that straightforward explanation does not account for a process that sometimes occurs when cells divide. Called gene conversion, the copy of a gene from Mom can replace the one from Dad, or vice versa, making the two copies identical.

In a new study published in the American Journal of Human Genetics, University of Pennsylvania researchers Joseph Lachance and Sarah A. Tishkoff investigated this process in the context of the evolution of human populations. They found that a bias toward certain types of DNA sequences during gene conversion may be an important factor in why certain heritable diseases persist in populations around the world.

Lachance is a postdoctoral fellow at Penn in Tishkoff's lab and will be starting his own lab at Georgia Tech in January. Tishkoff is a Penn Integrates Knowledge Professor with appointments in the Perelman School of Medicine's Department of Genetics and the School of Arts & Sciences' Department of Biology.

The study pins on the question of why humans have a genetic predilection for certain diseases. Some reasons have become clear to scientists. The Amish, for example, have a higher risk of several genetic diseases due in part to a phenomenon called founder effects, whereby certain genes rise to prevalence in populations that originated with a relatively small number of individuals.

Other genetic diseases can become relatively common if some aspect about them is advantageous.

"The classic example is sickle-cell anemia," Lachance said. "It's an evolutionary trade-off because people with one copy of a sickle-cell mutation are highly protected from malaria."

Less is known, however, about gene conversion events, which became the focus of Lachance and Tishkoff's study. Previously, researchers have found that during gene conversion DNA is more likely to be retained and copied if the allele that differs contains either a guanine (G) or a cytosine (C) nucleotide. Conversely, the DNA is more likely to be converted, or replaced, if the allele contains an adenine (A) or thymine (T).

"This bias is very small," Lachance said. "It's like a very slightly weighted coin. But over generations and across huge amounts of the genome, flipping the coin over and over again, we thought we would start to see an effect at the population level.

To see if this genetic preference, known as the GC bias, was having an effect, Lachance and Tishkoff analyzed the genomic sequences of 25 people -- five from each of five groups representing diverse populations. They identified 7.5 million single nucleotide polymorphisms, or SNPs, which are mutations involving a single nucleotide, and grouped them according to whether a change represented a shift from a G or C to an A or T or the reverse.

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DNA 'bias' may keep some diseases in circulation, biologists show