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"I knew there would be rare variation but had no idea therewould be so much of it," said the senior author of theresearch, John Novembre, an assistant professor of ecology andevolutionary biology and of bioinformatics at UCLA. A team of life scientists studied 202 genes in 14,002 people. Thehuman genome contains some 3 billion base pairs; the scientistsstudied 864,000 of these pairs. While this is only a small part ofthe genome, the sample size of 14,002 people is one of the largestever in a sequencing study in humans. "Our results suggest there are many, many places in the genomewhere one individual, or a few individuals, have somethingdifferent," Novembre said. "Overall, it is surprisinglycommon that there is a rare variant in the population. "This study doesn't tell us how to cure a particular diseasebut suggests that disease in general may be caused by rarevariants, and if you're trying to find the genetic basis ofdisease, it's important to focus on those variants. Understandingthe genetic basis of disease provides clues to how the diseaseswork and clues about how to treat them." The scientists discovered one genetic variant every 17 bases, whichwas a dramatically higher rate than they expected, said Novembre, apopulation geneticist who is a member of UCLA's interdepartmentalprogram in bioinformatics. Most of the time, only one person has the genetic variant and theother 14,001 do not. "We saw lots of that," he said. "We discovered thereare many places in these 202 genes where there is variation andonly a few individuals differ from the whole group, or only onediffers. We also see evidence that a substantial fraction of theserare genetic variants appear to be deleterious in a long-termevolutionary sense and might impact disease." The research team included Daniel Wegmann, a former UCLApostdoctoral scholar in Novembre's laboratory and a co-first authorof the study; Darren Kessner, a UCLA graduate student in thebioinformatics interdepartmental Ph.D. program; colleagues from theUniversity of Michigan, Ann Arbor (in fields including humangenetics and biostatistics); and geneticists from internationalhealth care company GlaxoSmithKline, including project leaderMatthew Nelson. The UCLA life scientists were involved in thepopulation genetic analysis of the data. In the study, 10,621 people had one of 12 diseases, includingcoronary artery disease, multiple sclerosis, bipolar disorder,schizophrenia, osteoarthritis and Alzheimer's disease; 3,381 didnot have any of the diseases. "The large sample size allows us to see patterns with moreclarity than ever before," Novembre said. "If rarevariants are like distant stars, this kind of large sample size islike having the Hubble Telescope; it's allowing us to see more thanbefore. We see a ton of rare variation, and these rare variantsmore often make changes to proteins than not. In that way, thisstudy has important implications for the genetic basis of diseasein humans. It's consistent with the idea that many diseases may bepartly caused by rare variants." Human population growth helps to explain the large number ofgenetic variants, the scientists said. "The fact that we see so many rare variants is in part due tothe fact that human populations have been growing veryrapidly," Novembre said. "Because the human populationhas grown so much, the opportunity for mutations to occur has alsogrown. Some of the variants we are seeing are very young, dating topopulation growth since the invention of agriculture and even theIndustrial Revolution; this growth has created many opportunitiesfor mutation in the genome because there are so many transmissionsof chromosomes from parent to child in large populations." The scientists isolated and sequenced the pieces of DNA from the202 genes. They estimated mutation rates from population genetic data, whichhas only rarely been done before. "We have been able to estimate mutation rates for each of thegenes, which has been difficult to do with smaller samplesizes," Novembre said. "In future research, we can studymutation rates not just in these 202 genes, but genome-wide." Sequencing technologies are advancing rapidly, he said. "Whatseemed like science fiction in the past is science today." Rare genetic variants would not have been detectable in mostprevious studies, whose samples usually had fewer than 1,000people. Typically, in population genetics, it is difficult to estimatemutation rates separately from population sizes, but when you getto very large sample sizes, you can estimate the two separately,Novembre said. "We estimate 202 mutation rates, one for each gene," hesaid. "We show that the mutation rate varies from gene togene. Follow-up studies may be able to reveal more about whatfactors affect mutation rates." Rare genetic variants are frequently geographically localized tosmall pockets around the globe rather than being widespread,Novembre said. In the image accompanying this release, each vertical linerepresents one of the 202 genes. For each gene, the scientistsplotted, at the top of the image, the number of genetic variantsthat have a frequency greater than 0.5 percent. When variants aregreater than 0.5 percent, previous studies have been able to findmost of them. "With our large sample size, we can detect variants at afrequency less than 0.5 percent, and we see all of these, whichhave never been seen before," Novembre said. "Previousstudies have examined the tip of the iceberg of genetic variation,but there is all this rare variation that has been below thesurface, below our threshold of detection. Now, with large samplesizes, we can see a more complete picture of human geneticdiversity." The genetic code has changes that are "nonsynonymous"(they change the meaning of a protein) and "synonymous"(they don't change the meaning of a protein). "We see many nonsynonymous changes amongst the rare variants,and these are plausibly affecting disease in humans, though in waysthat are not yet well understood," Novembre said. I am an expert from steel-trussbridge.com, while we provides the quality product, such as Soft Surface Layer Manufacturer , China Floating Pontoon Bridge, Steel Truss Bridge,and more.
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