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First Direct Measurement of Mutation Rate in Humans Accomplished

by Rajashri on August 30, 2009 at 12:46 PM
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 First Direct Measurement of Mutation  Rate  in Humans Accomplished

The first direct measurement of the general rate of genetic mutation at individual DNA letters in humans has been accomplished by an international team of 16 scientists.

The team sequenced the same piece of DNA - 10,000,000 or so letters or 'nucleotides' from the Y chromosome - from two men separated by 13 generations, and counted the number of differences.

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Among all these nucleotides, they found only four mutations.

The new research shows that we all carry 100-200 new mutations in our DNA.

This is equivalent to one mutation in each 15 to 30 million nucleotides. Fortunately, most of these are harmless and have no apparent effect on our health or appearance.
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"The amount of data we generated would have been unimaginable just a few years ago," said Dr Yali Xue from the Wellcome Trust Sanger Institute and one of the project's leaders.

"But finding this tiny number of mutations was more difficult than finding an ant's egg in the emperor's rice store," he added.

Team member Qiuju Wang recruited a family from China who had lived in the same village for centuries.

The team studied two distant male-line relatives, separated by thirteen generations, whose common ancestor lived two hundred years ago.

To establish the rate of mutation, the team examined an area of the Y chromosome.

The Y chromosome is unique in that, apart from rare mutations, it is passed unchanged from father to son; so mutations accumulate slowly over the generations.

Despite many generations of separation, researchers found only 12 differences among all the DNA letters examined.

The two Y chromosomes were still identical at 10,149,073 of the 10,149,085 letters examined.

Of the 12 differences, eight had arisen in the cell lines used for the work. Only four were true mutations that had occurred naturally through the generations.

The researchers used next-generation sequencing to establish the order of letters on the two Y chromosomes and then compared these to the Y chromosome reference sequence.

Having identified 23 candidate single letter changes in the DNA, they amplified the regions containing these candidates and checked the sequences using the standard Sanger method.

A total of four naturally occurring mutations were confirmed.

Knowing this number of mutations, the length of the area that they had searched and the number of generations separating the individuals, the team was able to calculate the rate of mutation.

"These four mutations gave us the exact mutation rate - one in 30 million nucleotides each generation - that we had expected," said the study's coordinator, Chris Tyler-Smith, also from The Wellcome Trust Sanger Institute.

Source: ANI
RAS
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