25 March 2011

Genome sequencing: another record

Genome reading is a competition of machines
Cholera vibrio was completely deciphered in one hour
Alexander Spirin, Independent Newspaper

Reading the first human genome took 15 years, and this year scientists are celebrating a decade since the publication of his first draft – an approximate version. This was followed by sequencing–sequences of individual chromosomes and the creation of next-generation sequencing machines (Next Generation). One California company, leading in this field, announced that this fall it will introduce its new automatic sequencer to the market at a cost of only 125 thousand dollars, which is less than 30 thousand dollars. it will read the genome of any person in less than a month.

An alternative option is also proposed – to read DNA by passing individual molecules through the pores in graphene, or – another option – to read the genome "letter by letter". At the same time, differences in the physical properties of nucleotides, or "letters" of the gene code, will be recorded, which will give the desired result within a second or two. But for now, these are all pilot developments that still need to be implemented "in hardware".

Nikolai Eroshenko, who with colleagues from Harvard proposed to determine DNA sequences at the time of their synthesis on microchips, suggested going a slightly different way. Thus, it is possible to eliminate the main drawback of the methods of the second generation, which, unlike the "classics", is associated with a fairly high percentage of errors.

And here came a stunning message about the appearance of a third-generation machine that made it possible to read the genome of a cholera vibrio in an hour. The machine still costs over 700 thousand dollars, but the first "fast" sequencers cost about a million. It should also be noted that the reading of the microbial genome was carried out in real time, that is, it was similar to a video message via Skype. In addition, the new machine makes it possible to "see" epigenetically modified nucleotides. (Epigenesis implies chemical "editing" of the letters of the gene code after the end of DNA synthesis; such epigenetic modification of genes leads to their silencing or activation.)

The speed of the new machine is associated with the elimination of a time-consuming and long-term operation (called "amplification"). The method of the third generation allows you to stand over the soul of the enzyme synthesizing the DNA molecule. Therefore, it requires only one molecule, and not many, for which amplification, or "multiplication", amplification is needed. In addition, it can be used to read DNA in hard-to-reach places of chromosomes, which is now being done almost manually. The creators of the new sequencer promise that by 2013 they will learn to read the genome in a quarter of an hour!

The next arrival of cholera in South America happened in 1991. Scientists analyzed the genomes of the pathogen of that year, two Asian outbreaks of 2002 and 2008, as well as the "new" Haitian – a total of 23 different strains, or variants. Comparison of genomes allowed us to find out that the outbreak of the disease that broke out on the island after the earthquake last year was caused by the Asian strain of El Tor, which came from Bangladesh, and not by South American isolates. Apparently, it's about rice supplied through humanitarian aid. It is unclear, however, why cholera occurred in a part of the island that was not affected by the disaster.

Critics and skeptics admit that a new machine created in California (in Menlo Park) gives chains of read DNA that are 10 times longer than those that are being made today, which makes it possible to speed up the process of reading the genome many times. However, it also has more errors: the reading accuracy does not exceed 85%, while the second-generation machines have this indicator above 99%. If no significant breakthroughs are made in the principles of operation of the new device, then with its help it will be possible to quickly and successfully read the genomes of microbes that are ten times smaller than a human. But no one doubts that this niche will be in demand. Recall that in the 10 years since the publication of the first draft of the human genome, science today has almost two hundred fully read genomes of various people around the world. The work is carried out within the framework of the "1000 genomes" project.

Portal "Eternal youth" http://vechnayamolodost.ru25.03.2011

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