Gene variation means ‘perfection’ impossible

No human carries a perfect genome with each person carrying between 250 and 300 genetic variations that could cause a gene to stop working properly say geneticists

The project – an international public-private consortium and a pilot study for the 1000 Genomes Project – has produced the most comprehensive map of genetic variations, estimated to contain approximately 95% of the genetic differences of any person on Earth.

Three pilot studies used next-generation DNA sequencing technologies to systematically characterise variation in the whole genome of 179 people of either European, West African or East Asian ancestry. They also sequenced the protein-coding genes of 697 people. Each region was sequenced several times, generating 4.5 terabases – 4.5 million million base letters.

“The amount of information delivered by this first stage of the project is remarkable,” said Richard Durbin of the Wellcome Trust Sanger Institute and co-chair of the consortium, “In less than two years, we identified 15 million single-letter changes, 1 million small deletions or insertions and 20,000 larger variants.”

Durbin said around 8 million of these variants have never been seen before. Researchers discovered that on average each person carries 250-300 genetic changes that could prevent a gene from working correctly, and 50 to 100 variations that have been associated with inherited disease.

“Having a systematic catalogue of human variation changes the way we can study human genetics, much in the same way as having a catalogue of human genes did,” said Dr Paul Flicek from EMBL-EBI. “Among other things, it also gives us a platform for analysing the connections between genes and an individual’s disease risk.”

The project aims to provide a comprehensive public resource that supports researchers studying genetic variation. Differences can be caused by a single base being replaced by a different one – single nucleotide polymorphism – or can be as complex as whole sections of a chromosome being duplicated or relocated. By comparing many individuals to one another, and one population to other populations, researchers hope to create a map of all genetic variation. All the variants can now be tested for their association with any given disease or trait, such as susceptibility to addictive behaviour.

“This work shows the power of very recent advances in sequencing to generate maps of genetic variation that bridge different scales,” said Jan Korbel from EMBL who helped analyse larger variants, “It’s an exciting first step which paves the way for looking at the relationship between genetic variations and diseases like cancer.”