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

August 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: Cellular sentinel prevents cell division when the right machinery is not in place

Related Stories

A triangular protein pump

July 6, 2015

Ludwig Maximilian University of Munich researchers have elucidated the structure of a molecular machine with an atypical triangular shape that is involved in peroxisome biogenesis, and characterized its conformation in different ...

Recommended for you

Machine Translates Thoughts into Speech in Real Time

December 21, 2009

(PhysOrg.com) -- By implanting an electrode into the brain of a person with locked-in syndrome, scientists have demonstrated how to wirelessly transmit neural signals to a speech synthesizer. The "thought-to-speech" process ...

Quantum Theory May Explain Wishful Thinking

April 14, 2009

(PhysOrg.com) -- Humans don’t always make the most rational decisions. As studies have shown, even when logic and reasoning point in one direction, sometimes we chose the opposite route, motivated by personal bias or simply ...

0 comments

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.