MULTICELLULAR EUKARYA GENOME SEQUENCING PROJECTS
(see also bioinformatic tools for nucleic acids)

Scientists cannot reliably recover DNA that is > 50,000 years old. To investigate older sequences, researchers have to rely on computer programs that infer backwards from present-day animals (computational genomics). A software takes into account substitutions, deletions and insertions : an algorithm can simulate evolution of a hypothetical portion of ancestral mammalian DNAand use the sequence of descendants to recreate the original ancestor with 98% accuracy. When this algorithm is used to work out a small region of the genome (that codes for 10 genes) of the common ancestor of 19 modern mammals, including the pig, human and rat thought to be a shrew-like animal that lived > 70 million years ago, the human sequence has lost only 11% of bases, whereas in rodents around 39% have been deleted, probably because rats and similar animals go through generations more quickly, so they accumulate mutations fasterref.

The degraded DNA of ancient cave bears has been sequenced, despite the fact that many considered the genetic information unrecoverable. The achievement leads researchers to think they might be able to perform the same trick with DNA from ancient human relatives, such as the Neanderthals. In the past, scientists have managed to retrieve genetic material for analysis from animals or humans that died in icy or desert environments, because these allow for good preservation. But the remains of animals and humans are mostly found in caves, and are heavily decomposed. The DNA from such specimens is usually mixed up with DNA from soil microbes and later cave inhabitants, making it difficult to sequence. The standard practice for sequencing genes involves making numerous copies of the initial sample through PCR. Subjecting ancient DNA to this does not produce good results because PCR picks up and duplicates the sequences of modern animals more efficiently. This means that bits of contaminating DNA often drown out samples from the prehistoric animal. To overcome this challenge, Noonan and his colleagues decided to skip the replicating step and directly sequence the tiny amount of DNA extracted from 2 Austrian cave-bear bones that are > 40,000 years old. To make sure each portion of DNA was really from the bears rather than a contaminating source, they compared each sequence produced with the genome of the dog, a modern relative of the bear. The technologies needed to examine such tiny amounts of DNA directly, along with the reference genome from the dog, have become available to scientists only recently. Nearly 6% of the sequences analysed from one of their animal samples belonged to ancient bear: an unexpectedly large amount. The rest of the DNA probably came from soil microbes or the palaeontologists handling the bones. The same technique should work on Neanderthal samples of about the same age or younger. But challenges remain. Most important, it will be much harder to weed out contaminating DNA from the people who excavated the Neanderthal samples, as both sets of DNA will come from humansref

Human chromosomes : G-banding, diagram and R-banding























18 new species have been selected by NHGRIfor whole genome sequencingref : The 18 species will be added to the institute's waiting list for genome sequencing, which currently features the kangaroo, cow, and a host of flies and fungi. Sequencing will be done at the five centres of the institute's Large-Scale Sequencing Research Network across the United States, using the high-speed 'shotgun' method developed for the Human Genome Project. Once work begins, the sequences should all take about a year to complete.
What next for the geneticist who seems to have sequenced everything? After piecing together DNA sequences from the oceans, his dog and of course, humans, the genome pioneer Craig Venter has announced his next plan - to find out what microbes are blowing around in New York's air. The Air Genome Project will filter bugs from the air in midtown Manhattan, the United States' most densely populated area. Researchers from the J. Craig Venter Institute in Rockville, Maryland, will collect dozens of samples both indoors and outside, before sifting through them for fragments of microbial DNA. The move follows a similar project by Venter's company to sequence genetic information from a region of ocean near Bermuda. That project identified some 1.3 million new genes and at least 1,800 new species of marine microorganism. The Air Genome Project will work in a similar way to its marine predecessor. Having filtered the air, Venter's team will use the 'shotgun' method, which involves analysing small segments of DNA and piecing them together into longer strings by matching up their overlapping ends. The scientists thus hope to identify more organisms than the old-fashioned method of simply leaving a culture dish on a windowsill and then incubating it to see what grows. Many microbial species cannot be cultured in the lab, so this method would not reveal their presence. Even with the help of shotgun sequencing, it will be difficult to piece together entire genome sequences for all but the most abundant organisms. His own approach is to look at certain genes that all bacteria share, albeit in slightly different versions, to work out what species are present in a sample. To collect the samples, a filter has been designed that will sift through some 1,400 m3 of air each day. Having tested the device on top of their building in Rockville, the researchers have now installed it on a 40-storey office block in the Big Apple, although its precise whereabouts is a secret. Identifying the microbes that flit through our air and into our lungs could be a useful step towards combating urban diseases such as asthma. Many bacteria and viruses in the air elicit destructive immune responses and we would like to explore these. Urban areas across the world are likely to harbour many of the same species

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