Maize HapMap2 identifies extant variation from a genome in flux.这是徐老师最近在NG上新发表的文章.上篇博文有过介绍.当然那个介绍是面向大众的.专业人员,得读全文.全文里才有真正值得自己学习的东西.比如这个东西:read-depth variants (RDVs),老实说,我是第一次注意到这个东西.不明白当然的搜下了,搜到这篇文章Sensitive and accurate detection of copy number variants using read depth of coverage.结合上下文,知道这是一种检测结构变异的方法(结构变异:structural variation).更重要的是这篇文章:Structural variation: the genome's hidden architecture(http://www.nature.com/nmeth/journal/v9/n2/full/nmeth.1858.html?WT.ec_id=NMETH-201202)Nature Methods,2012,Vol(9),133-137.

      这篇文章有段:"The Austrian monk Gregor Mendel may have founded the science of genetics, but his ideas now limit genomic studies, according to Jim Lupski, a molecular geneticist at Baylor College of Medicine in Texas. “Mendelian thinking is to genetics as Newtonian thinking is to physics. We saw a whole new world when Einstein came along.”

      为什么孟德尔的观点限制了基因组学研究?"According to Mendelian principles, individuals inherit exactly two copies of each gene—one from each parent. Genes on sex chromosomes have long been recognized as exceptions, but genetic deletions and duplications also break the rules, and in ways that are much harder to track."呵呵,这是高人的推论.

      直接原因:In the early 1990s, Lupski and colleagues found that the hereditary neuropathy Charcot-Marie-Tooth disease was associated not with a flawed version of a particular genetic region but instead with the presence of an extra copy of the normal version. “We all believed Mendel for many, many years, but when you have a duplication, you are triallelic rather than biallelic,” he says. Experts were so unwilling to accept the idea of a disease caused by a gene-dosage effect that both Science and Nature declined even to send his paper out for review, he recalls. When Lupski did publish, in Cell, his lab used four independent methods to substantiate his conclusions within a skeptical scientific community¹.(基因的剂量效应可能产生新的表型)

    Despite additional findings like this, and the sequencing of the human genome, studies are still built on Mendelian assumptions, says Lupski. The concept of paired homologous chromosomes is taught in high school biology; the term 'paralogous', which refers to clusters of identical or near-identical sequences at different chromosomal locations within the same genome, is much more obscure. Genome-wide association studies, which find correlations between a disease population and specific genetic variation, tend to take diploidy as the default. Even microarrays designed to assess copy number generally assume that most individuals carry exactly two copies of any particular region, which can throw off some calculations.

    And copy-number variation is just one type of a class of previously overlooked differences now collectively known as structural variation.  This catch-all category includes insertions, duplications, deletions, inversions, recurring mobile elements, and other rearrangements, now usually defined as those covering 50 or more base pairs (Fig. 1). (The number is arbitrary; earlier definitions set the number at 1,000 base pairs until sequencing technologies capable of detecting smaller variants drove it down.)  

     There is a growing recognition that structural variation is pervasive and important. Since the publication of seminal papers^{2, 3} in 2004, the numbers of references to structural variation in the scientific literature and entries in the curated archive Database of Genomic Variants have soared (Fig. 2). It is now recognized that, in terms of the number of nucleotides, structural variation accounts for more differences between human genomes than the more extensively studied single-nucleotide differences. A 2010 study estimated that such “non-SNP variation” totaled about 50 megabases per human genome⁴.(植物里对这个的研究报道好象还比较少,徐老师这篇算是比较有影响的一篇,当然具体的影响力,显现还需要时间.这篇文章中有个观点:This suggests that structural variation, captured here by RDVs, may have an important role in phenotypic variation.吾深以为然).

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