1.基因组的结构和变异2.分子标记连锁图谱构建基因3.QTL定位的原理和方法4.QTL精细定位5.基因和QTL的可隆5.1插入突变方法5.2图位克隆的方法(含比较图位克隆)5.3候选基因法6.资源评估和利用7.分子标记辅助选择(含分子设计育种)8.转基因8.1转基因体系和实证研究8.2转基因的生态学安全研究9.比较基因组9.1标记水平比较基因组9.2序列水平的比较研究9.3性状水平的比较研究9.4功能比较研究10.***优势研究10.1遗传学解释10.2分子生物学解释11.分子进化(主要是玉米进化)12.基于连锁不平衡的关联分析12.1实证研究12.2方法学研究13.基因组研究中的一些新技术运用13.1DNA芯片技术13.2 DNA shuffling13.3Gene Trap13.4 Gene therapy in plants13.5 TILLING 技术1.植物基因组的结构和变异在越来越多的植物基因组被测完后,该研究的重要性逐渐显现,该方面的文章可以说是汗牛充栋.在玉米方面该领域的大牛是Buckler, ES; Messing, J, Dooner HK, Doebley J ; Gaut, BS.1. Buckler, E. S., Gaut, B. S. and McMullen, M. D. (2006) Molecular and functional diversity of maize. Curr. Opin. Plant Biol. 9, 172-176这是关于玉米基因组结构的REVIEW文章,先了解大概,在细读研究文章.其任何2个玉米自交系之间的遗传变异大于人和大猩猩之间的差异的经典论断充分说明玉米变异的广泛性.最近因为人类基因组研究的进展而似乎可以改写.2.Messing J, Dooner HK. Organization and variability of the maize genome. Curr Opin Plant Biol.2006 Apr;9(2):157-63两位大牛的联合REVIEW, 值得一读.3.Goff S A, Ricke D, Lan T H, Presting G, Wang R, Dunn M, Glazebrook J, Sessions A, Oeller P, Varma H, Hadley D, Hutchison D, Martin C, Katagiri F, Lange B M, Moughamer T, Xia Y, Budworth P, Zhong J, Miguel T, et al. A Draft Sequence of the Rice Genome Oryza sativa L. ssp. japonica. Science, 2002, 296: 92-100大家或许都知道这篇文章,但我相信看完的不多,尽管全基因组测序的文章许多,强烈建议大家读这篇,讨论写的太好了.同期中国测序的文章就相形见拙许多,当然之后水稻精细图谱的公布,这篇文章也可以读读.4. International Rice Genome Sequencing Project. The map-based sequence genome. nature, 2005, 436: 793-8005.Fu H H, Dooner H K. Intraspecific violation of genetic colinearity and its implications in maize. Proc Natl Acad Sci USA, 2002, 99: 9573-9578改文章给我的启示许多,基因的存在和缺失也是等位基因的一种形式就是其一,尽管后来该文章的结论不断被修正.6.Song R, Messing J: Gene expression of a gene family in maize based on noncolinear haplotypes. Proc Natl Acad Sci USA 2003, 100:9055-9060.宋任涛代表作之一, 与Fu的文章有异曲同工之妙,给***优势提供了新的解释.7.Brunner S, Fengler K, Morgante M, Tingey S, Rafalski A: Evolution of DNA sequence non-homologies among maize inbreds. Plant Cell 2005, 17:343-360.5,6工作的基础上提供了更多的数据8. Lai J, Li Y, Messing J, Dooner HK: Gene movement by Helitron transposons contributes to the haplotype variability of maize. Proc Natl Acad Sci USA 2005, 102:9068-9073.赖锦盛的代表工作之一,为玉米基因组的扩张提供了全面的解释.9. Lai J, Ma J, Swigonova Z, Ramakrishna W, Linton E, Llaca V, Tanyolac B, Park YJ, Jeong OY, Bennetzen JL et al.: Gene loss and movement in the maize genome. Genome Res 2004, 14:1924-1931部分阐述了玉米基因组的结构的成因,更多的是插入而不是缺失.10. Morgante M, Brunner S, Pea G, Fengler K, Zuccolo A, Rafalski A:Gene duplication and exon shuffling by helitron-like transposons generate intraspecies diversity in maize.Nat Genet 2005, 37:997-1002与8讲的同一个故事.11.Tenaillon MI, Sawkins MC, Long AD, Gaut RL, Doebley JF, Gaut BS: Patterns of DNA sequence polymorphism along chromosome 1 of maize (Zea mays ssp. mays L.). Proc Natl Acad Sci USA 2001, 8:9161-9166该数据表明,在玉米基因组大约只保留了其祖先大刍草60%的遗传变异.12.Messing J, Bharti AK, Karlowski WM, Gundlach H, Kim HR, Yu Y, Wei F, Fuks G, Soderlund CA, Mayer KF et al.: Sequence composition and genome organization of maize. Proc Natl Acad Sci USA 2004, 101:14349-14354玉米有59000个基因的预测就出自此文.13. Bruggmann R, Bharti AK, Gundlach H, Lai J, Young S, Pontaroli AC, Wei F, Haberer G, Fuks G, Du C, Raymond C, Estep MC, Liu R, Bennetzen JL, Chan AP, Rabinowicz PD, Quackenbush J, Barbazuk WB, Wing RA, Birren B, Nusbaum C, Rounsley S, Mayer KF, Messing J. Uneven chromosome contraction and expansion in the maize genome. Genome Res. 2006 Oct;16(10):1241-5114.Emrich SJ, Li L, Wen TJ, Yandeau-Nelson MD, Fu Y, Guo L, Chou HH, Aluru S, Ashlock DA, Schnable PS. Nearly Identical Paralogs: Implications for Maize (Zea mays L.) Genome Evolution.Genetics. 2007 Jan;175(1):429-39Schnable 提出的NIP概念给我们以后的关联分析和其他一系列研究提出了新的挑战,尽管在玉米基因组的频率只有1%.15. Fu Y, Emrich SJ, Guo L, Wen TJ, Ashlock DA, Aluru S, Schnable PS.Quality assessment of maize assembled genomic islands (MAGIs) and large-scale experimental verification of predicted genes. Proc Natl Acad Sci U S A. 2005 23;102(34):12282-7.看看什么是MAGI，也是Schnable的贡献，其超大的课题组（在美国而言）和永不疲倦的精力让他文章如麻，而且牛文不断。

2.分子标记连锁图谱构建和基因定位该领域的理论发展最大贡献者当然属于Lincoln,而玉米连锁图的构建, 全世界多个实验室都有重要贡献,比如Coe EH, 法国的Falque, 和访问过农大的Schnable.这尽管是一项非常基础的工作,但非常重要.从下面文章的清单不难看出,只要做的好有特色,同样能发好文章.其它各个重要的动植物都走过类似的历程，在植物里这一领域的研究，玉米应该还是比较靠前的，因为它不但重要，而且也算得上模式植物.16. Lincoln S, Daly M, Lander E. Mapping genetic mapping with MAPMAKER/EXP3.0. Cambridge: MA: Whitehead institute Technical Report, 1992尽管新的方法不断涌现,但MAPMAKER 目前仍然是连锁图构建和基因定位的经典方法.17.Helentjaris T, Slocum M, Wright S, Schaefer A, Niehhuis J. Construction of genetic linkage maps in maize and tomato using restriction fragment length polymorphisms. Theor Appl Genet, 1986, 72: 761–769玉米第一张分子标记连锁图18.Burr, B., Burr, F., Thompson, K.H., Albersten, M. and Stuber, C. W. (1988) Gene mapping with recombinant inbreds in maize. Genetics 118, 519–526玉米第一张RIL图谱19.Beavis, W. D., and Grant, D. (1991) A linkage map based on information from 4 F2 populations of Maize (Zea mays L.). Theor. Appl. Genet. 82, 636–644玉米的F2图谱20.Gardiner, J. M., Coe, E. H., Melia-Hancock, S., Hoisington, D. A. and Chao, S. (1993) Development of a core RFLP map in maize using an immortalized F2 population. Genetics 134, 917–930.玉米第一张IF2图谱(注意不同于我们提到的IF2群体)21.Gardiner, J., Schroeder, S., Polacco, M. L., Sanchez-Villeda, H., Fang, Z., Morgante, M., Landewe, T., Fengler, K., Useche, F., Hanafey, M., Tingey, S., Chou, H., Wing, R., Soderlund, C. and Coe Jr., E.H. (2004) Anchoring 93 971 maize expressed sequence tagged unigenes to the bacterial artificial chromosome contig map by two-dimensional overgo hybridization. Plant Physiol. 134, 1317-1326.遗传图谱和物理图谱的整合22.Davis, G. L., McMullen, M. D., Baysdorfer, C., Musket, T., Grant, D., Staebell, M., Xu, G., Polacco, M., Koster, L., Melia-Hancock, S., Houchins, K., Chao, S., and Coe Jr, E. H. (1999). A maize map standard with sequenced core markers, grass genome reference points and 932 expressed sequence tagged sites (ESTs) in a 1736-locus map. Genetics 152, 1137–117223.Natalya S, McMullen M D, Schultz L, Schroeder S, Sanchez-Villeda H, Gardiner J, Bergstrom D, Houchins K, Melia-Hancock S, Musket T, Duru N, Polacco M, Edwards K, Ruff T, Register J C, Brouwer C, Thompson R, Velasco R, Chin E, Lee M, Woodman-Clikeman W, Long MJ, Liscum E, Cone K, Davis G, Coe EH. Development and mapping of SSR markers for maize. Plant Mol Bio, 2002, 48: 463-481几张玉米的高密度连锁图24.Falque, M., Décousset, L., Dervins, D., Jacob, A. M., Joets, J., Martinant, J. P., Raffoux, X., Ribière, N., Ridel, C., Samson, D., Charcosset, A. and Murigneux, A. (2005) Linkage Mapping of 1454 New Maize Candidate Gene Loci. Genetics 170, 1957-1966玉米的大规模基因定位及连锁图谱25.Fu Y, Wen TJ, Ronin YI, Chen HD, Guo L, Mester DI, Yang Y, Lee M, Korol AB, Ashlock DA, Schnable PS. Genetic dissection of intermated recombinant inbred lines using a new genetic map of maize.Genetics. 2006 Nov;174(3):1671-83.玉米的大规模的IDP图谱而目前各类标记(IDP, Gene, cDNA, SSR, RFLP, SNP等)都被整合到IBM图谱,并有机与玉米物理图谱进行了整合,详细信息参考MAIZEGDB.3.QTL定位的原理和应用该领域让我们记住一个名字,那就是毕业于华中农业大学,现供职于北卡州立大学的曾昭邦教授.他1994年发表在Genetics的文章,已经是QTL定位领域不可超越的传奇,其正面引用应该接近或者超过1000次.他也是大陆动物遗传育种专业留学生中在美国唯一的正教授.他多次回国和母校讲学,2000年在华农讲学,在分子数量遗传学门外徘徊的我根本听不懂他在讲什么,错失良机.其发展的QTL定位软件几经改进,可以说在数量遗传学领域路人皆知.26. Zeng Z B. Precision mapping of quantitative trait loci. Genetics, 1994, 136: 1457–1468经典中的经典,但我估计认真读过的人不多,尤其新近入门的同学.同时在此基础上, 还发展了一系列分析方法.27. Cockerham CC and Z. B. Zeng Design III With Marker Loci.Genetics 1996 143: 1437-1456重新对Stuber的数据进行分析,认为超显性都是拟超显性.为我们的遗传设计提出了新的指导思想,但听从的不多.28. Chen-Hung Kao, Zhao-Bang Zeng, and Robert D. Teasdale Multiple Interval Mapping for Quantitative Trait Loci. Genetics 1999 152: 1203-1216提出了MIM的算法,为我们估计总的遗传效应提供了方法.29.Chen-Hung Kao and Zhao-Bang Zeng Modeling Epistasis of Quantitative Trait Loci Using Cockerham's Model Genetics 2002 160: 1243-1261提出了上位性的算法.30. Lander E S, Botstein S. Mapping Mendelian factors underlying quantitative traits using RFLP linkage maps. Genetics, 1989, 121: 185–199经典的区间作图法, CIM是该基础上发展而来,贡献卓越,引用超过2000次.31. Wang D L, Zhu J, Li Z K, Paterson A H. Mapping QTLs with epistatic effects and QTL environment interactions by mixed linear model approaches. Theor Appl Genet, 1999, 99: 1255-1264浙江大学的朱军教授也是该领域的著名人物,在CIM基础上发展出MCIM(混合线性模型)的方法,也是一个重要的贡献,同时也提出条件QTL的定位方法,经典文章有下面2篇.32. Zhu J. Analysis of conditional genetic effects and variance components in developmental genetics. Genetics, 1995, 141: 1633–1639老鼠尾巴的长度和体重有什么关系?呵呵,这篇文章就研究这个,至少问题有趣.33. Yan J Q, Zhu J, He C X, Benmoussa M, Wu P. Molecular dissection of developmental behavior of plant height in rice (Oryza sativa L.). Genetics, 1998, 150: 1257-1265株高发育性状的QTL定位,这篇文章给了我启示,而让我的论文有了点副产品,想了解改领域的基本知识,可以参考我2003科学通报的文章.34. Wei-Ren Wu, Wei-Ming Li, Ding-Zhong Tang, Hao-Ran Lu, and A. J. Worland Time-Related Mapping of Quantitative Trait Loci Underlying Tiller Number in Rice. Genetics 1999 151: 297-303 现在浙江大学的吴为人教授对时间序列的QTL分析也有贡献,但没有好的软件出来.关于QTL定位的应用文章枚不胜举,下面2篇文章是经典.35. Schon, C. C., Utz, H. F., Groh, S., Truberg, B., Openshaw, S. and Melchinger, A. E. (2004) Quantitative trait locus mapping based on resampling in a vast maize testcross experiment and its relevance to quantitative genetics for complex traits. Genetics 167, 485-498该研究用了超过1000个单株的超大群体,和19个环境的田间数据. 估计目前这2个数字仍然是无法超越的.36. Laurie, C. C., Chasalow, S. D., LeDeaux, J. R., McCarrol, R., Rush, D., Hauge, B., Lai, C. Q., Clark,D., Rocheford, T. R. and Dudley, J. W. (2004) The genetic architecture of response to long-term artificial selection for oil concentration in the maize kernel. Genetics 168, 2141-2155该研究用了高油玉米长期选择的极端材料和大群体,所以对效应值小的QTL有很好的估计.37. 章元明. 作物QTL 定位方法研究进展. 科学通报, 19, 2223-2231.我认为是迄今关于这方面最好的中文综述.尤其关于经典QTL的定位介绍的比较详细和到位,是对初进该领域的研究者最好的开门文章,几乎囊括了所有经典文章.我们常常知道QTL定位要选择显著标记对背景控制?原因是什么,多少合适?如果不选或者选多了会出现什么问题?如果理解了这些理论问题,大家对QTL定位的结果就会有更深刻的认识,而不会简单堆积结果了.QTL定位下一步的一个发展方向将是:1) Nested Association Mapping and Diallel Association Mapping, 也就是结合连锁和连锁不平衡的分析方法,该方法有Buckler首先提出来并付诸实践,相信不久就有实际实验结果的文章出来,下一步是第一篇方法探讨文章.38. Benjamin Stich, Jianming Yu, Albrecht E. Melchinger, Hans-Peter Piepho, Friedrich Utz, Hans P Maurer, and Edward S Buckler Power to detect higher-order epistatic interactions in a metabolic pathway using a new mapping strategy. Genetics 2006: doi: 10.1534/genetics.106.0670332) eQTL定位这也是将来QTL定位的一个重要内容,也是联系遗传学上QTL定位和表达水平基因表达谱研究的桥梁.在动物方面（人，小鼠等）相关研究进展很多，下一波就是植物了。