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法国、美国、意大利等国科研人员在新一期英国《自然》杂志上报告说，这名男性患者从3年前开始接受基因疗法。当时他18岁，患有β型地中海贫血症。这种病
由基因缺陷引起，患者自身不能生成正常的红细胞，因此需要通过输血来保持血液的供养等功能。这名患者从3岁开始输血，严重时每个月都要输血。
在基因疗法试验中，研究人员先利用患者自身的骨髓造血干细胞培养出包括红细胞在内的血液细胞，然后使用病毒作载体，将无缺陷的基因引入这些细胞中，再用化学手段去除多余细胞，只留下基因缺陷得到修正的红细胞，最后将这些红细胞移植回患者体内。
结果显示，患者自身生成正常红细胞的能力逐渐上升，在接受治疗一年后就不再需要输血了。现在该患者虽然仍有轻微贫血症状，但迄今一直不需要输血，并且已经有了一份全职的厨师工作，这说明基因疗法取得了初步成功。
不过也有专家对这一结果持谨慎态度，比如认为试验成功与这名患者自身的一些生理特点有关，可能难以在其他患者身上复制成功经验。试验中使用的病毒带来了一
定的副作用，有引发癌症的可能。但是总的来说，这次试验打开了使用基因疗法治疗地中海贫血症的大门，为许多患者带来了希望。
据研究者介绍，β型地中海贫血症多见于地中海地区和东南亚。现有治疗手段除了定期输血外，还有移植造血干细胞等，但通常很难找到匹配的干细胞捐献者，因此基因疗法成为一个新的研究方向。
Marina Cavazzana-Calvo, Emmanuel Payen, Olivier Negre, Gary Wang, Kathleen Hehir, Floriane Fusil, Julian Down, Maria Denaro, Troy Brady, Karen Westerman, Resy Cavallesco, Beatrix Gillet-Legrand, Laure Caccavelli, Riccardo Sgarra, Leila Maouche-Chrétien, Françoise Bernaudin, Robert Girot, Ronald Dorazio, Geert-Jan Mulder, Axel Polack, Arthur Bank, Jean Soulier, Jérôme Larghero, Nabil Kabbara, Bruno Dalle, Bernard Gourmel, Gérard Socie, Stany Chrétien, Nathalie Cartier, Patrick Aubourg, Alain Fischer, Kenneth Cornetta, Frédéric Galacteros, Yves Beuzard, Eliane Gluckman, Frederick Bushman, Salima Hacein-Bey-Abina & Philippe Leboulch
Nature Volume:467, Pages: 318–322 Date published:(16 September 2010)DOI:doi:10.1038/nature09328 Received 27 January 2010 Accepted 28 June 2010
The β-haemoglobinopathies are the most prevalent inherited disorders
worldwide. Gene therapy of β-thalassaemia is particularly challenging
given the requirement for massive haemoglobin production in a
lineage-specific manner and the lack of selective advantage for
corrected haematopoietic stem cells. Compound βE/β0-thalassaemia is the most common form of severe thalassaemia in southeast Asian countries and their diasporas1, 2. The βE-globin
allele bears a point mutation that causes alternative splicing. The
abnormally spliced form is non-coding, whereas the correctly spliced
messenger RNA expresses a mutated βE-globin with partial instability1, 2. When this is compounded with a non-functional β0 allele, a profound decrease in β-globin synthesis results, and approximately half of βE/β0-thalassaemia patients are transfusion-dependent1, 2.
The only available curative therapy is allogeneic haematopoietic stem
cell transplantation, although most patients do not have a
human-leukocyte-antigen-matched, geno-identical donor, and those who do
still risk rejection or graft-versus-host disease. Here we show that, 33
months after lentiviral β-globin gene transfer, an adult patient with
severe βE/β0-thalassaemia dependent on monthly transfusions since early childhood has become transfusion independent for the past 21 months. Blood haemoglobin is maintained between 9 and 10 g dl−1,
of which one-third contains vector-encoded β-globin. Most of the
therapeutic benefit results from a dominant, myeloid-biased cell clone,
in which the integrated vector causes transcriptional activation of HMGA2 in erythroid cells with further increased expression of a truncated HMGA2
mRNA insensitive to degradation by let-7 microRNAs. The clonal
dominance that accompanies therapeutic efficacy may be coincidental and
stochastic or result from a hitherto benign cell expansion caused by
dysregulation of the HMGA2 gene in stem/progenitor cells.
http://www.nature.com/nature/journal/v467/n7313/abs/nature09328.html
一个国际科研团队7日发布报告称，他们已经对家养火鸡的基因组90%以上的区域完成测序。
研究人员表示，短期内，测序结果就可以提供对火鸡产量、质量、发育、生殖以及抗病至关重要的基因的信息，科学家可以据此培育出肥瘦、口感不同的火鸡品种，提高火鸡疾病预防和治疗手段。
这项测序的大部分数据来自火鸡的10个最大的染色体。研究人员表示，通过这项始于2008年的项目，他们已经发现了数千个此前不为鸟类科学家所知的基因，此前研究甚少的火鸡性染色体的测序结果也令人感兴趣。
来自澳大利亚、英国、德国、荷兰、韩国、西班牙以及美国的研究人员参与了火鸡基因组测序工作。相关研究成果下周将发表在美国《公共科学图书馆·生物学》杂志网络版上。
生物谷推荐英文摘要：
PLoS Biology 8(9): e1000475. doi:10.1371/journal.pbio.1000475
Multi-Platform Next-Generation Sequencing of the Domestic Turkey (Meleagris gallopavo): Genome Assembly and Analysis
A synergistic combination of two next-generation sequencing platforms
with a detailed comparative BAC physical contig map provided a
cost-effective assembly of the genome sequence of the domestic turkey
(Meleagris gallopavo). Heterozygosity of the sequenced source genome
allowed discovery of more than 600,000 high quality single nucleotide
variants. Despite this heterozygosity, the current genome assembly (~1.1
Gb) includes 917 Mb of sequence assigned to specific turkey
chromosomes. Annotation identified nearly 16,000 genes, with 15,093
recognized as protein coding and 611 as non-coding RNA genes.
Comparative analysis of the turkey, chicken, and zebra finch genomes,
and comparing avian to mammalian species, supports the characteristic
stability of avian genomes and identifies genes unique to the avian
lineage. Clear differences are seen in number and variety of genes of
the avian immune system where expansions and novel genes are less
frequent than examples of gene loss. The turkey genome sequence provides
resources to further understand the evolution of vertebrate genomes and
genetic variation underlying economically important quantitative traits
in poultry. This integrated approach may be a model for providing both
gene and chromosome level assemblies of other species with agricultural,
ecological, and evolutionary interest.
Rami A. Dalloul1#, Julie A. Long2#, Aleksey V. Zimin3#, Luqman
Aslam4, Kathryn Beal5, Le Ann Blomberg2, Pascal Bouffard6, David W.
Burt7, Oswald Crasta8,9, Richard P. M. A. Crooijmans4, Kristal Cooper8,
Roger A. Coulombe10, Supriyo De11, Mary E. Delany12, Jerry B. Dodgson13,
Jennifer J. Dong14, Clive Evans8, Karin M. Frederickson6, Paul Flicek5,
Liliana Florea15, Otto Folkerts8,9, Martien A. M. Groenen4, Tim T.
Harkins6, Javier Herrero5, Steve Hoffmann16,17, Hendrik-Jan Megens4,
Andrew Jiang12, Pieter de Jong18, Pete Kaiser19, Heebal Kim20, Kyu-Won
Kim20, Sungwon Kim1, David Langenberger16, Mi-Kyung Lee14, Taeheon
Lee20, Shrinivasrao Mane8, Guillaume Marcais3, Manja Marz16,21, Audrey
P. McElroy1, Thero Modise8, Mikhail Nefedov18, Cédric Notredame22, Ian
R. Paton7, William S. Payne13, Geo Pertea15, Dennis Prickett19, Daniela
Puiu15, Dan Qioa23, Emanuele Raineri22, Magali Ruffier24, Steven L.
Salzberg25, Michael C. Schatz25, Chantel Scheuring14, Carl J. Schmidt26,
Steven Schroeder27, Stephen M. J. Searle24, Edward J. Smith1,
Jacqueline Smith7, Tad S. Sonstegard27, Peter F. Stadler16,28,29,30,31,
Hakim Tafer16,30, Zhijian (Jake) Tu32, Curtis P. Van Tassell27,33,
Albert J. Vilella5, Kelly P. Williams8, James A. Yorke3, Liqing Zhang23,
Hong-Bin Zhang14, Xiaojun Zhang14, Yang Zhang14, Kent M. Reed34*
导读：美国研究人员在8月27日发表的Science杂志上发表研究成果称，他们首次绘制了两周蚂蚁的全基因组序列图。
生物谷推荐原文索引<<<
Science DOI: 10.1126/science.1192428
Genomic Comparison of the Ants Camponotus floridanus and Harpegnathos saltator
Roberto
Bonasio,1,* Guojie Zhang,2,3,* Chaoyang Ye,4,* Navdeep S. Mutti,5,*
Xiaodong Fang,3,* Nan Qin,3,* Greg Donahue,4 Pengcheng Yang,3 Qiye Li,3
Cai Li,3 Pei Zhang,3 Zhiyong Huang,3 Shelley L. Berger,4,Danny
Reinberg,1,6, Jun Wang,3,7, Jürgen Liebig5,
美国科学家表示，他们首次绘制出了两种蚂蚁的全基因组序列图。此举可为科学家更好地了解人类衰老以及行为表现提供帮助。
该研究项目的负责人、纽约大学兰贡医疗中心的生化学教授丹尼·赖因伯格说：“蚂蚁是绝对的社会动物，蚂蚁个体的生存要依靠蚂蚁群体，这与我们人类非
常相似。无论是工蚁、兵蚁还是蚁后，蚂蚁都是绝佳的研究对象，对蚂蚁的研究有助于我们理解表观遗传学如何影响人类衰老以及行为表现。”该项研究成果刊登在
《科学》（Science）杂志上。
从2008年开始，纽约大学兰贡医疗中心的科学家便与来自宾夕法尼亚州、亚利桑那州以及中国的同行合作研究杰唐跳蚁和佛罗里达木匠蚁的表观遗传学差异，以更好对包括人类在内的其他动物进行分析。
这项计划完成后，蚂蚁便成为继蜜蜂之后第二种被破译基因组序列的社会性昆虫。
在蚂蚁种群中，一般的工蚁寿命从三周到一年不等。而蚁后的寿命要比工蚁长10倍多。该项研究主要针对蚂蚁群体中寿命长短不一的现象来分析表观遗传学从中起到的作用和影响。
在将杰唐跳蚁和佛罗里达木匠蚁进行比较之后，科学家发现它们有33%的基因与人类基因相同，有20%是独特基因。
“在对这两种蚂蚁进行研究后，我们被工蚁所进化出来的不同行为以及不同角色所深深吸引了，”赖因伯格说，“群体中的每只蚂蚁的生命都是从同一个原点
开始，它们的基因结构是相同的。因而令它们做出符合其社会阶层行为的迥然不同的脑信号一定是由表观遗传学机制所决定的。这一发现可以帮助我们更好地了解表
观遗传学对人类大脑功能的影响。”（生物谷Bioon.com）
英文摘要<<<
The organized societies of ants include short-lived worker castes
displaying specialized behavior and morphology and long-lived queens
dedicated to reproduction. We sequenced and compared the genomes of two
socially divergent ant species: Camponotus floridanus and Harpegnathos
saltator. Both genomes contained high amounts of CpG, despite the
presence of DNA methylation, which in non-Hymenoptera correlates with
CpG depletion. Comparison of gene expression in different castes
identified up-regulation of telomerase and sirtuin deacetylases in
longer-lived H. saltator reproductives, caste-specific expression of
microRNAs and SMYD histone methyltransferases, and differential
regulation of genes implicated in neuronal function and chemical
communication. Our findings provide clues on the molecular differences
between castes in these two ants and establish a new experimental model
to study epigenetics in aging and behavior
导读：8月29日，一国际科研小组报道称他们绘出了广受人们喜爱的“金冠苹果”的基因组草图。这将有助于从基因水平上分析苹果性状，培育更多苹果新品种。
生物谷推荐原文索引<<<
Nature Genetics doi:10.1038/ng.654
The genome of the domesticated apple (Malus × domestica Borkh.)
Riccardo Velasco etc.
据新华社报道称，苹果基因组中含有7亿多个碱基对，其中有大段重复的基因。研究人员说，也许是大量的重复基因使苹果具有较多的染色体数目。与苹果同属蔷薇科的桃和草莓等水果的染色体数在7到9之间，而苹果的染色体数为17。
通过基因分析，研究人员还查明了苹果的“身世”。苹果与其他水果“亲戚”之间的进化分叉可能发生在五六千万年前，而这正是地球上发生大灾难的时候。这场大灾难导致恐龙灭绝。苹果的“祖先”植物可能是为了适应大灾难后的环境，逐步发生基因变化，最终进化成了今天的苹果树。
正是这些与其他水果不同的基因决定了苹果独特的风味和口感。此次绘出的苹果基因组草图，将有助于今后采用基因手段改良苹果，比如培育更脆、更多汁的苹果品种。
苹果是世界上最重要的水果之一。据介绍，现在全球每年苹果产量超过6000万吨。（生物谷Bioon.com）
英文摘要
We report a high-quality draft genome sequence of the domesticated
apple (Malus × domestica). We show that a relatively recent (>50
million years ago) genome-wide duplication (GWD) has resulted in the
transition from nine ancestral chromosomes to 17 chromosomes in the
Pyreae. Traces of older GWDs partly support the monophyly of the
ancestral paleohexaploidy of eudicots. Phylogenetic reconstruction of
Pyreae and the genus Malus, relative to major Rosaceae taxa, identified
the progenitor of the cultivated apple as M. sieversii. Expansion of
gene families reported to be involved in fruit development may explain
formation of the pome, a Pyreae-specific false fruit that develops by
proliferation of the basal part of the sepals, the receptacle. In apple,
a subclade of MADS-box genes, normally involved in flower and fruit
development, is expanded to include 15 members, as are other gene
families involved in Rosaceae-specific metabolism, such as transport and
assimilation of sorbitol.
对两个品种蚂蚁的基因组的比较给了科学家们一些线索：究竟是什么决定了一只蚂蚁的命运是成为工蚁还是蚁后。不同等级的蚂蚁有着相同的基因蓝图，但它们会因为影响其基因表达的“表观遗传学”的变化而发育成为完全不同的个体。在佛罗里达弓背蚁（Camponotus floridanus）的群体中，只有蚁后才会产下受精卵；当该蚁后死亡时，该蚂蚁的群体也随之死亡。
该蚁群中的其它蚂蚁或是主要工蚁或是次要工蚁，它们有着不同的生理学和行为学差异。相反，在印度跳蚁(Harpegnathos saltator)
的群体中，蚁后与工蚁的身体差别没有那么明显，而且在蚁后死亡时，某个工蚁会进而成为蚁后。Roberto
Bonasio以及一个国际性同事的团队现在对这两种蚂蚁的基因组进行了测序。他们对基因表达进行了比较并发现了可能与诸如RNA介导的信号转导和甲基化等基因调节的表观变化有关的差异。本文的作者说，这一研究除了对造成这两种蚂蚁的不同等级间存在分子差异的原因提供了线索之外，它还建立了一个研究衰老和行为的表观遗传学的新的实验模型。
生物谷推荐原文出处：
Science DOI: 10.1126/science.1192428
Genomic Comparison of the Ants Camponotus floridanus and Harpegnathos saltator
Roberto Bonasio,1,* Guojie Zhang,2,3,* Chaoyang Ye,4,*
Navdeep S. Mutti,5,* Xiaodong Fang,3,* Nan Qin,3,* Greg Donahue,4
Pengcheng Yang,3 Qiye Li,3 Cai Li,3 Pei Zhang,3 Zhiyong Huang,3 Shelley
L. Berger,4, Danny Reinberg,1,6, Jun Wang,3,7, Jürgen Liebig5,
The organized societies of ants include short-lived worker castes
displaying specialized behavior and morphology and long-lived queens
dedicated to reproduction. We sequenced and compared the genomes of two
socially divergent ant species: Camponotus floridanus and Harpegnathos
saltator. Both genomes contained high amounts of CpG, despite the
presence of DNA methylation, which in non-Hymenoptera correlates with
CpG depletion. Comparison of gene expression in different castes
identified up-regulation of telomerase and sirtuin deacetylases in
longer-lived H. saltator reproductives, caste-specific expression of
microRNAs and SMYD histone methyltransferases, and differential
regulation of genes implicated in neuronal function and chemical
communication. Our findings provide clues on the molecular differences
between castes in these two ants and establish a new experimental model
to study epigenetics in aging and behavior.
1 Department of Biochemistry, New York University School of Medicine, 522 First Avenue, New York, NY 10016, USA.
2
Chinese Academy of Sciences–Max Planck Junior Research Group, State Key
Laboratory of Genetic Resources and Evolution, Kunming Institute of
Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China.
3 Beijing Genomics Institute–Shenzhen, Shenzhen 518083, China.
4 Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
5 School of Life Sciences, Arizona State University, Tempe, AZ 85287, USA.
6 Howard Hughes Medical Institute, New York University Medical School, New York, NY 10016, USA.
7 Department of Biology, University of Copenhagen, Copenhagen DK-2200, Denmark.
本期Nature发表了大堡礁海绵Amphimedon queenslandica的基因组草图，同时还有比较基因组分析结果。
海绵被认为处在动物界最早的分支上，是“真”动物或“真后生动物”的一个姐妹类群。因此，海绵对多细胞性起源的研究做出了重要贡献。分析表明，该基
因组在内容、结构和组织上都与其他动物基因组非常相似，并且显示了与动物的起源和早期演化相关的基因组事件，包括“泛后生动物”转录因子、信号通道和结构
基因的出现、扩张和分化。
生物谷推荐原文出处：
Nature doi:10.1038/nature09201
The Amphimedon queenslandica genome and the evolution of animal complexity
Mansi
Srivastava,Oleg Simakov,Jarrod Chapman,Bryony Fahey,Marie E. A.
Gauthier,Therese Mitros,Gemma S. Richards,Cecilia Conaco,Michael
Dacre,Uffe Hellsten,Claire Larroux,Nicholas H. Putnam,Mario Stanke,Maja
Adamska,Aaron Darling,Sandie M. Degnan,Todd H. Oakley,David C.
Plachetzki,Yufeng Zhai,Marcin Adamski,Andrew Calcino,Scott F.
Cummins,David M. Goodstein,Christina Harris,Daniel J. Jackson,et al
Sponges are an ancient group of animals that diverged from other
metazoans over 600 million years ago. Here we present the draft genome
sequence of Amphimedon queenslandica, a demosponge from the Great
Barrier Reef, and show that it is remarkably similar to other animal
genomes in content, structure and organization. Comparative analysis
enabled by the sequencing of the sponge genome reveals genomic events
linked to the origin and early evolution of animals, including the
appearance, expansion and diversification of pan-metazoan transcription
factor, signalling pathway and structural genes. This diverse ‘toolkit’
of genes correlates with critical aspects of all metazoan body plans,
and comprises cell cycle control and growth, development, somatic- and
germ-cell specification, cell adhesion, innate immunity and
allorecognition. Notably, many of the genes associated with the
emergence of animals are also implicated in cancer, which arises from
defects in basic processes associated with metazoan multicellularity.
美国农业研究局（ARS）的科研人员近日发明了一种新的方法来破译本土草原上被广泛研究的一种草——柳枝稷（Switchgrass）的遗传特性。ARS位于加利福尼亚西部研究中心的克里斯蒂安.托比亚斯（Christian Tobias）及其同事在《遗传学》（Genetics）上发表的柳枝稷遗传图谱，有望加快寻找能够提高柳枝稷作为生物能源可靠来源的基因。
柳枝稷目前主要作为家畜的牧草，并可以用来修复贫瘠的土壤。但是近年来，由于它可以通过燃烧发电并且可以转变成乙醇，逐渐引起科研人员的兴趣。
为了绘制柳枝稷遗传图谱，研究人员采用了全同胞图谱绘制法（full-sib
mapping），即以柳枝稷推广品种Kanlow为母本，ARS培育的品种Alamo为父本进行杂交，得到了238棵F1代；进一步从F1群体中提取
DNA并利用1000多个遗传标记完成了图谱的绘制。此图谱将柳枝稷的基因组分成了18个不同的组，每组的基因位于同一条DNA链上。
弄清柳枝稷的遗传结构能够带来巨大的好处。为使柳枝稷作为一种生物燃料进一步推广，科学家正在探索提高其产量并使其细胞壁更容易破裂的方法，这是从纤维质生产乙醇必要的一步。
柳枝稷的遗传图谱有助于发现与细胞壁组成、作物产量和其他有用特性相关的基因。科学家通过比较柳枝稷和水稻、高粱及其他植物的遗传图谱，可以更好地理解基因组，找到和植物中特殊品质相关的基因。
Genetics doi:10.1534/genetics.110.113910
Complete Switchgrass Genetic Maps Reveal Subgenome Collinearity, Preferential Pairing and Multilocus Interactions
Miki Okada*,1, Christina Lanzatella*, Malay C. Saha, Joe Bouton, Rongling Wu and Christian M. Tobias*,2
* U. S. Department of Agriculture–Agricultural Research Service
(USDA–ARS), Genomics and Gene Discovery Research Unit, Western Regional
Research Center, Albany, California 94710, Samuel Roberts Noble
Foundation, Inc., Forage Improvement Division, Ardmore, Oklahoma 73401
and Division of Biostatistics, Pennsylvania State University, Hershey,
Pennsylvania 17033 ；2 Corresponding author: Genomics and Gene Discovery
Research Unit, Western Regional Research Center, 800 Buchanan St.,
Albany, CA 94710.
Polyploidy is an important aspect of the evolution of flowering
plants. The potential of gene copies to diverge and evolve new functions
is influenced by meiotic behavior of chromosomes leading to segregation
as a single locus or duplicated loci. Switchgrass (Panicum virgatum)
linkage maps were constructed using a full-sib population of 238 plants
and SSR and STS markers to access the degree of preferential pairing and
the structure of the tetraploid genome and as a step toward
identification of loci underlying biomass feedstock quality and yield.
The male and female framework map lengths were 1645 and 1376 cM with 97%
of the genome estimated to be within 10 cM of a mapped marker in both
maps. Each map coalesced into 18 linkage groups arranged into nine
homeologous pairs. Comparative analysis of each homology group to the
diploid sorghum genome identified clear syntenic relationships and
collinear tracts. The number of markers with PCR amplicons that mapped
across subgenomes was significantly fewer than expected, suggesting
substantial subgenome divergence, while both the ratio of coupling to
repulsion phase linkages and pattern of marker segregation indicated
complete or near complete disomic inheritance. The proportion of
transmission ratio distorted markers was relatively low, but the male
map was more extensively affected by distorted transmission ratios and
multilocus interactions, associated with spurious linkages.
尽管全基因组测序的费用正在下降，但外显子组测序仍是一项研究孟德尔疾病的好技术，研究人员如是说，他们第一次使用外显子组测序鉴定出一种罕见病中的新生（de novo）、显性突变。
研究人员使用这种方法来鉴定Schinzel-Giedion综合征中的致病突变，Schinzel-Giedion综合征是一种导致严重的智力缺陷、肿瘤高发以及多种先天性畸形的罕见病。大部分患病个体在10岁前死亡。
研究者通过捕获四个患病婴儿的外显子组，并测序，文章发表在上个月的《自然-遗传学》（Nature Genetics）上。在
所有四个病例中，他们都发现了SETBP1基因的杂合突变，而他们又利用Sanger测序对婴儿父母的SETBP1基因进行验证，发现这种突变在父母身上
不存在，这暗示Schinzel-Giedion是一种由新生突变引起的显性罕见病。研究人员利用Sanger测序鉴定出另外八个病例中相同基因的突变。
“这个突变在父母身上不存在，并且它也未在正常个体的其它地方发现。因此它与疾病有很强的关联，”文章的第一作者，内梅亨大学（Radboud
University）人类遗传学系的助理教授Jorvis Veltman告诉In
Sequence。“目前，我们已经发现12个在特定位点有突变的患者。”
一些研究显示，外显子组测序能用于鉴定孟德尔疾病中的隐性遗传突变。例如，冷泉港实验室的研究人员利用外显子组测序鉴定出Joubert综合征的致病突变，而华盛顿大学的研究小组利用外显子组测序定位了米勒综合征的疾病基因（系统生物学研究所的研究人员还通过全基因组测序独立地证实了这些基因）。
美国国立人类基因组研究院负责大规模测序的项目主管Lu Wang认为，内梅亨的研究发现了新生显性突变，是“外显子组测序应用的不错扩展”，她本人与这项研究没有关系。“这让不断增加的外显子组测序所鉴定的疾病列表又增加了一项。”
研究人员使用SureSelect和SOLiD对四位患者的外显子组进行测序，平均覆盖度为43倍，读长为50
bp，每个个体产生了2.7-3
GB可作图的序列数据。他们在每个个体中鉴定出5,351个非同义SNP。他们聚焦于全部四位患者都携带变异体的12个基因，最终将候选基因缩小至1个。
由于Schinzel-Giedion早已被认为是由新生显性突变引起的，因此缩小候选基因的列表就与隐性遗传疾病略有不同。研究人员寻找不存在与父母中的杂合变异体，而不是寻找每位亲本携带一个等位基因的纯合变异体。
一方面，Veltman表示，寻找杂合变异体要略微棘手一些，因为个体携带的杂合变异体比纯合变异体要多得多。但另一方面，他认为，由于突变被认为
是显性的，那么与dbSNP和其它正常变异体的目录比较要容易一些。Veltman表示，对于隐性突变，常常有存在于正常的健康个体中的可能性，因此，当
你使用dbSNP来缩小候选变异体时，你可能不知不觉地排除了致病突变。而对于显性突变，这种可能性要小得多。
Veltman认为，致病突变的鉴定有可能让临床医生进行疾病的产前检测，同时为有着相似表型的其它疾病提供了线索。例如，Schinzel-
Giedion的一个特征是神经上皮肿瘤的高发——此肿瘤会影响感觉和中枢神经系统。Veltman表示，他们正在研究此疾病中的基因，看它是否相关。
Veltman还提到，另一个有趣的发现是SETBP1基因的所有突变都发生在12
bp内。这是不寻常的，暗示突变有着功能获得的影响，改变了蛋白的功能，Veltman表示如果其它相关疾病也被那个基因的突变所影响，他预计那些突变将
会是更加难以捉摸。因此，就神经上皮肿瘤而言，他们正在寻找此基因的12 bp片段以外的突变。
除了研究其它更常见综合征中基因的影响，Veltman表示研究小组正在对更多孟德尔疾病以及更复杂的疾病如智力缺陷和孤独症进行测序。
一些人认为，全基因组测序费用的下降将让外显子组测序很快过时。然而，Veltman表示他的研究小组计划继续在SOLiD平台上使用外显子组测序。
Veltman表示：“目前，（外显子组测序）是一种非常好的方法。我们知道如何阐释编码区的变异，它比编码区外要好得多。当全基因组测序变得更加普及且阐释清晰时，我们将开始使用那个。”
NHGRI的Wang也同意外显子组测序比全基因组测序有优势，特别是对罕见的单基因疾病。不仅仅是费用更低，数据的阐释也更为简单。
“外显子组测序在稀有突变的发现上有很多优势，”Wang表示。“目前有7000种假定的孟德尔疾病。我敢说外显子组测序将会在很长一段时间内使用。”
外显子组测序技术也比全基因组测序走得更远，Wang补充道，不仅仅是测序，还包括捕获技术和数据分析。“应用外显子组测序来发现疾病相关基因的时
机是对的，”她表示。“（Veltman的小组）能够鉴定出新生显性突变的事实是个很不错的例子，说明了就鉴定稀有突变而言，外显子组测序能走得多远。”
生物谷推荐原文出处：
Nature Genetics doi:10.1038/ng.581
De novo mutations of SETBP1 cause Schinzel-Giedion syndrome
Alexander
Hoischen1,14, Bregje W M van Bon1,14, Christian Gilissen1,14, Peer
Arts1, Bart van Lier1, Marloes Steehouwer1, Petra de Vries1, Rick de
Reuver1, Nienke Wieskamp1, Geert Mortier2, Koen Devriendt3, Marta Z
Amorim4, Nicole Revencu5, Alexa Kidd6, Mafalda Barbosa7, Anne Turner8,
Janine Smith9, Christina Oley10, Alex Henderson11, Ian M Hayes12,
Elizabeth M Thompson13, Han G Brunner1, Bert B A de Vries1 & Joris A
Veltman1
Schinzel-Giedion syndrome is characterized by severe mental
retardation, distinctive facial features and multiple congenital
malformations; most affected individuals die before the age of ten. We
sequenced the exomes of four affected individuals (cases) and found
heterozygous de novo variants in SETBP1 in all four. We also identified
SETBP1 mutations in eight additional cases using Sanger sequencing. All
mutations clustered to a highly conserved 11-bp exonic region,
suggesting a dominant-negative or gain-of-function effect.
德国比勒费尔德大学7月9日报告说，一个有德国研究者参加的国际研究小组最近完成了对最简单的多细胞生物团藻的基因组测序。科研人员希望以此帮助探寻单细胞生物向多细胞生物演变的奥秘。
单细胞生物怎么能演变为多细胞生物乃至人这样高度复杂的生物，一直是生物研究的重要课题。一个由德国、美国、加拿大和日本科研人员组成的研究小组选择从团藻入手，因为团藻的细胞种类十分简单。此外，团藻还有一个单细胞近亲——莱茵衣藻，后者的基因组测序已在2007年完成。
在美国《科学》(Science)
杂志7月9日发表的最新研究报告中，上述研究小组发现团藻的基因组有大约1．4亿个碱基对，包含大约1．45万个基因，比人类基因总数仅少不到一半。参与
这项研究的比勒费尔德大学专家说，研究小组在比较团藻和莱茵衣藻基因组时意外发现，尽管这两种生物的复杂程度和生命史存在很大差异，二者的基因组却有相似
的蛋白编码潜能。与莱茵衣藻相比，专家在团藻细胞内只发现了很少该生物特有的基因。科研人员由此推断，从单细胞生物演变为多细胞生物并非必需大幅提高基因的数目，在这种演变中，基因如何以及何时编码合成特定的蛋白才具有决定意义。
德国专家说，在单细胞生物向多细胞生物演变的分子机理研究方面，团藻基因组测序是了解这一分子机理的重要一步。长期而言，研究简单生物的分子机理有助于更好地理解人类等复杂生物的进化史。
第一个古代人类基因组测序完成或用于法医鉴定领域
Nature：美科学家完成稻瘟病菌基因组测序
Nature：褐藻（Ectocarpus）基因组测序完成
PLoS Biology：老鼠全基因组测序图公布
个人基因组测序将蓬勃发展—生物谷专访Knome公司总裁及CEO
全基因组测序——低至3万元
生物谷推荐原文出处：
Science DOI: 10.1126/science.1188800
Genomic Analysis of Organismal Complexity in the Multicellular Green Alga Volvox carteri
Simon
E. Prochnik,1,* James Umen,2,*, Aurora M. Nedelcu,3 Armin Hallmann,4
Stephen M. Miller,5 Ichiro Nishii,6 Patrick Ferris,2 Alan Kuo,1 Therese
Mitros,7 Lillian K. Fritz-Laylin,7 Uffe Hellsten,1 Jarrod Chapman,1 Oleg
Simakov,8 Stefan A. Rensing,9 Astrid Terry,1 Jasmyn Pangilinan,1
Vladimir Kapitonov,10 Jerzy Jurka,10 Asaf Salamov,1 Harris Shapiro,1
Jeremy Schmutz,11 Jane Grimwood,11 Erika Lindquist,1 Susan Lucas,1 Igor
V. Grigoriev,1 Rüdiger Schmitt,12 David Kirk,13 Daniel S. Rokhsar1,7,
The multicellular green alga Volvox carteri and its morphologically
diverse close relatives (the volvocine algae) are well suited for the
investigation of the evolution of multicellularity and development. We
sequenced the 138–mega–base pair genome of V. carteri and compared its
~14,500 predicted proteins to those of its unicellular relative
Chlamydomonas reinhardtii. Despite fundamental differences in organismal
complexity and life history, the two species have similar
protein-coding potentials and few species-specific protein-coding gene
predictions. Volvox is enriched in volvocine-algal–specific proteins,
including those associated with an expanded and highly compartmentalized
extracellular matrix. Our analysis shows that increases in organismal
complexity can be associated with modifications of lineage-specific
proteins rather than large-scale invention of protein-coding capacity.
1 U.S. Department of Energy, Joint Genome Institute, Walnut Creek, CA 94598, USA.
2 The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
3 University of New Brunswick, Department of Biology, Fredericton, New Brunswick E3B 5A3, Canada.
4 Department of Cellular and Developmental Biology of Plants, University of Bielefeld, D-33615 Bielefeld, Germany.
5 Department of Biological Sciences, University of Maryland Baltimore County, Baltimore, MD 21250, USA.
6 Biological Sciences, Nara Women’s University, Nara-shi, Nara Prefecture 630-8506, Japan.
7
Center for Integrative Genomics, Department of Molecular and Cell
Biology, University of California at Berkeley, Berkeley, CA 94720, USA.
8 European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
9 Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany.
10 Genetic Information Research Institute, 1925 Landings Drive, Mountain View, CA 94043, USA.
11 HudsonAlpha Institute for Biotechnology, Huntsville, AL 35806, USA.
12 Department of Genetics, University of Regensburg, D-93040 Regensburg, Germany.
13 Department of Biology, Washington University in St. Louis, St. Louis, MO 63130, USA.
基因组大小，是指一个基因组中所拥有的DNA含量，是生物进化中最基本的、同时也是最复杂的遗传特征之一。例如，生物的复杂度并不与基因组大小有显著相关，即C值悖论。作为模式物种的红旗东方鲀和斑点绿河鲀是目前已知的具有最小基因组大小的脊椎动物（<400Mb，仅相当于人基因组大小的八分之一），对它们的全基因组测序分析发现，它们却具有与人相近的基因数目。正因为如此，河鲀基因组大小变化的研究引起关注。
在中国科学院水生生物研究所何舜平研究员的指导下，博士研究生郭宝成等通过构建刺河鲀（基因组大小为780Mb）的BAC文库和随机挑取克隆测序，在基因组水平对河鲀基因组大小变化进行了研究。对10个BAC克隆、长度776
kb的刺河鲀基因组测序分析发现，河鲀基因组大小变化同时表现为基因组同源区域和非同源区域长度的变化；基因组注释结果表明，内含子长度与河鲀基因组大小变化呈正相关，刺河鲀的内含子长度为566bp，统计上显著大于红旗东方鲀和斑点绿河鲀的内含子长度（435bp）；转座子序列的含量和家族在不同河鲀基
因组表现出明显的不同，并且转座子序列在不同河鲀基因组内的非等速积累是造成河鲀基因组大小变化的主要机制。
这一结果被国际同行评价为是对在河鲀基因组大小变化传统研究的重要补充和证明。
生物谷推荐原文出处：
BMC Genomics doi:10.1186/1471-2164-11-396
Genome size evolution in pufferfish: an insight from BAC clone-based Diodon holocanthus genome sequencing
Baocheng Guo , Ming Zou , Xiaoni Gan and Shunping He
Background
Variations in genome size within and between species
have been observed since the 1950s in diverse taxonomic groups. Serving
as model organisms, smooth pufferfish possess the smallest vertebrate
genomes. Interestingly, spiny pufferfish from its sister family have
genome twice as large as smooth pufferfish. Therefore, comparative
genomic analysis between smooth pufferfish and spiny pufferfish is
useful for our understanding of genome size evolution in pufferfish.
Results
Ten BAC clones of a spiny pufferfish Diodon holocanthus
were randomly selected and shotgun sequenced. In total, 776 kb of
non-redundant sequences without gap representing 0.1% of the D.
holocanthus genome were identified, and 77 distinct genes were
predicted. In the sequenced D. holocanthus genome, 364 kb is homologous
with 265 kb of the Takifugu rubripes genome, and 223 kb is homologous
with 148 kb of the Tetraodon nigroviridis genome. The repetitive DNA
accounts for 8% of the sequenced D. holocanthus genome, which is higher
than that in the T. rubripes genome (6.89%) and that in the Te.
nigroviridis genome (4.66%). In the repetitive DNA, 76% is retroelements
which account for 6% of the sequenced D. holocanthus genome and belong
to known families of transposable elements. More than half of
retroelements were distributed within genes. In the non-homologous
regions, repeat element proportion in D. holocanthus genome increased to
10.6% compared with T. rubripes and increased to 9.19% compared with
Te. nigroviridis. A comparison of 10 well-defined orthologous genes
showed that the average intron size (566 bp) in D. holocanthus genome is
significantly longer than that in the smooth pufferfish genome (435
bp).
Conclusion
Compared with the smooth pufferfish, D. holocanthus has
a low gene density and repeat elements rich genome. Genome size
variation between D. holocanthus and the smooth pufferfish exhibits as
length variation between homologous region and different accumulation of
non-homologous sequences. The length difference of intron is consistent
with the genome size variation between D. holocanthus and the smooth
pufferfish. Different transposable element accumulation is responsible
for genome size variation between D. holocanthus and the smooth
pufferfish.
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