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数量遗传学,第3.0版:自1987年以来我们取得了哪些进展,又将走向何方?

Quantitative genetics, version 3.0: where have we gone since 1987 and where are we headed?

作者信息

Walsh Bruce

机构信息

Departments of Ecology and Evolutionary Biology, Animal Sciences, Plant Sciences, Molecular and Cellular Biology, Epidemiology and Biostatistics, University of Arizona, Tucson, AZ 85721, USA.

出版信息

Genetica. 2009 Jun;136(2):213-23. doi: 10.1007/s10709-008-9324-0. Epub 2008 Sep 15.

Abstract

The last 20 years since the previous World Congress have seen tremendous advancements in quantitative genetics, in large part due to the advancements in genomics, computation, and statistics. One central theme of this last 20 years has been the exploitation of the vast harvest of molecular markers--examples include QTL and association mapping, marker-assisted selection and introgression, scans for loci under selection, and methods to infer degree of coancestry, population membership, and past demographic history. One consequence of this harvest is that phenotyping, rather than genotyping, is now the bottleneck in molecular quantitative genetics studies. Equally important have been advances in statistics, many developed to effectively use this treasure trove of markers. Computational improvements in statistics, and in particular Markov Chain Monte Carlo (MCMC) methods, have facilitated many of these methods, as have significantly improved computational abilities for mixed models. Indeed, one could argue that mixed models have had at least as great an impact in quantitative genetics as have molecular markers. A final important theme over the past 20 years has been the fusion of population and quantitative genetics, in particular the importance of coalescence theory with its applications for association mapping, scans for loci under selection, and estimation of the demography history of a population. What are the future directions of the field? While obviously important surprises await us, the general trend seems to be moving into higher and higher dimensional traits and, in general, dimensional considerations. We have methods to deal with infinite-dimensional traits indexed by a single variable (such as a trait varying over time), but the future will require us to treat much more complex objects, such as infinite-dimensional traits indexed over several variables and with graphs and dynamical networks. A second important direction is the interfacing of quantitative genetics with physiological and developmental models as a step towards both the gene-phenotype map as well as predicting the effects of environmental changes. The high-dimensional objects we will need to consider almost certainly have most of their variation residing on a lower (likely much lower) dimensional subspace, and how to treat these constraints will be an important area of future research. Conversely, the univariate traits we currently deal with are themselves projections of more complex structures onto a lower dimensional space, and simply treating these as univariate traits can result in serious errors in understanding their selection and biology. As a field, our future is quite bright. We have new tools and techniques, and (most importantly) new talent with an exciting international group of vibrant young investigators who have received their degrees since the last Congress. One cloud for concern, however, has been the replacement at many universities of plant and animal breeders with plant and animal molecular biologists. Molecular tools are now an integral part of breeding, but breeding is not an integral part of molecular biology.

摘要

自上届世界大会以来的过去20年里,数量遗传学取得了巨大进展,这在很大程度上归功于基因组学、计算科学和统计学的进步。过去20年的一个核心主题是对大量分子标记的利用——例如数量性状基因座(QTL)和关联作图、标记辅助选择和基因渐渗、选择位点扫描,以及推断共祖程度、群体归属和过去种群历史的方法。这一成果带来的一个后果是,在分子数量遗传学研究中,表型分析而非基因分型如今成为了瓶颈。同样重要的是统计学方面的进展,其中许多进展是为了有效利用这一丰富的标记宝库而开发的。统计学方面的计算改进,尤其是马尔可夫链蒙特卡罗(MCMC)方法,推动了许多此类方法的发展,混合模型计算能力的显著提升也起到了同样的作用。事实上,可以说混合模型在数量遗传学中的影响至少与分子标记一样大。过去20年的最后一个重要主题是群体遗传学与数量遗传学的融合,特别是溯祖理论的重要性及其在关联作图、选择位点扫描和种群历史推断中的应用。该领域的未来发展方向是什么?虽然显然会有重大惊喜等待着我们,但总体趋势似乎是朝着越来越高维的性状发展,以及更普遍地考虑维度问题。我们有方法处理由单个变量索引的无限维性状(例如随时间变化的性状),但未来将要求我们处理更复杂的对象,比如由多个变量索引且带有图和动态网络的无限维性状。第二个重要方向是数量遗传学与生理和发育模型的结合,这是朝着构建基因-表型图谱以及预测环境变化影响迈出的一步。我们几乎肯定需要考虑的高维对象,其大部分变异存在于较低(可能低得多)维子空间中,如何处理这些约束将是未来研究的一个重要领域。相反,我们目前处理的单变量性状本身是更复杂结构在低维空间上的投影,简单地将它们视为单变量性状可能会在理解其选择和生物学特性时导致严重错误。作为一个领域,我们的未来非常光明。我们拥有新的工具和技术,而且(最重要的是)有新的人才,包括一群令人兴奋的充满活力的年轻研究人员,他们自上届大会以来获得了学位。然而,一个令人担忧的问题是,许多大学中植物和动物育种家被植物和动物分子生物学家所取代。分子工具现在是育种不可或缺的一部分,但育种并非分子生物学不可或缺的一部分。

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