Why is Apert's syndrome so common when mutation rate is so low?

Aug 28, 2007

Aperts syndrome is a condition caused by a mutation that produces fused fingers and toes, and alters cranial development in affected children. It arises spontaneously, but why the mutation that causes this syndrome appears so frequently has been a mystery.

In a new study published this week in the open-access journal PLoS Biology, Jian Qin, Norman Arnheim, and colleagues from University of Southern California provide compelling evidence that suggests the syndrome is perpetuated because the cells carrying the mutation in the testes, and that give rise to sperm, out-replicate normal cells.

The researchers have shown that the single base-pair mutation responsible for over 60% of Aperts cases occurs with such high frequency not because the relevant gene sits at a “mutation hotspot,” but because mutant cells reproduce more frequently then normal cells.

The Aperts mutation occurs in cells with a frequency between 100 and a 1000 times higher than would be predicted given a standard mutation rate. The researchers have developed a new experimental approach that measures the anatomical distribution of the mutant cells in order to investigate the mutation’s origin. They dissected healthy testes to map where the mutations had arisen, and found that mutant cells were clustered together. This distribution cannot be explained by the “hotspot” model, which would place the mutant cells randomly throughout the organ.

Instead, this paper shows that clustered mutations arise because cells carrying the genetic change out-compete normal testes cells and tend to accumulate, producing more sperm that carry the mutation and a higher frequency of transmission.

Source: Public Library of Science

Explore further: Paralyzed man recovers some function following transplantation of OECs and nerve bridge

add to favorites email to friend print save as pdf

Related Stories

Pharmaceuticals and the water-fish-osprey food web

3 hours ago

Ospreys do not carry significant amounts of human pharmaceutical chemicals, despite widespread occurrence of these chemicals in water, a recent U.S. Geological Survey (USGS) and Baylor University study finds. ...

Recommended for you

Team untangles the biological effects of blue light

3 hours ago

Blue light can both set the mood and set in motion important biological responses. Researchers at the University of Pennsylvania's School of Medicine and School of Arts and Sciences have teased apart the ...

Mouse model provides new insight in to preeclampsia

3 hours ago

Worldwide, preeclampsia is a leading cause of maternal deaths and preterm births. This serious pregnancy complication results in extremely high blood pressure and organ damage. The onset of preeclampsia is associated with ...

Scientists unravel the mystery of a rare sweating disorder

3 hours ago

An international research team discovered that mutation of a single gene blocks sweat production, a dangerous condition due to an increased risk of hyperthermia, also known as heatstroke. The gene, ITPR2, controls a basic ...

User comments : 0