Meta-analysis of three genome-wide association studies identifies susceptibility loci for colorectal cancer at 1q41, 3q26.2, 12q13.13 and 20q13.33

Genome-wide association studies (GWAS) have identified ten loci harboring common variants that influence risk of developing colorectal cancer (CRC). To enhance the power to identify additional CRC risk loci, we conducted a meta-analysis of three GWAS from the UK which included a total of 3,334 affected individuals (cases) and 4,628 controls followed by multiple validation analyses including a total of 18,095 cases and 20,197 controls. We identified associations at four new CRC risk loci: 1q41 (rs6691170, odds ratio (OR) = 1.06, P = 9.55 × 10?1? and rs6687758, OR = 1.09, P = 2.27 × 10??, 3q26.2 (rs10936599, OR = 0.93, P = 3.39 × 10??), 12q13.13 (rs11169552, OR = 0.92, P = 1.89 × 10?1? and rs7136702, OR = 1.06, P = 4.02 × 10??) and 20q13.33 (rs4925386, OR = 0.93, P = 1.89 × 10?1?). In addition to identifying new CRC risk loci, this analysis provides evidence that additional CRC-associated variants of similar effect size remain to be discovered.     

A genome-wide association scan of tag SNPs identifies a susceptibility variant for colorectal cancer at 8q24.21

Much of the variation in inherited risk of colorectal cancer (CRC) is probably due to combinations of common low risk variants. We conducted a genome-wide association study of 550,000 tag SNPs in 930 familial colorectal tumor cases and 960 controls. The most strongly associated SNP (P = 1.72 x 10(-7), allelic test) was rs6983267 at 8q24.21. To validate this finding, we genotyped rs6983267 in three additional CRC case-control series (4,361 affected individuals and 3,752 controls; 1,901 affected individuals and 1,079 controls; 1,072 affected individuals and 415 controls) and replicated the association, providing P = 1.27 x 10(-14) (allelic test) overall, with odds ratios (ORs) of 1.27 (95% confidence interval (c.i.): 1.16-1.39) and 1.47 (95% c.i.: 1.34-1.62) for heterozygotes and rare homozygotes, respectively. Analyses based on 1,477 individuals with colorectal adenoma and 2,136 controls suggest that susceptibility to CRC is mediated through development of adenomas (OR = 1.21, 95% c.i.: 1.10-1.34; P = 6.89 x 10(-5)). These data show that common, low-penetrance susceptibility alleles predispose to colorectal neoplasia.     

Common variation near CDKN1A, POLD3 and SHROOM2 influences colorectal cancer risk

We performed a meta-analysis of five genome-wide association studies to identify common variants influencing colorectal cancer (CRC) risk comprising 8,682 cases and 9,649 controls. Replication analysis was performed in case-control sets totaling 21,096 cases and 19,555 controls. We identified three new CRC risk loci at 6p21 (rs1321311, near CDKN1A; P = 1.14 × 10(-10)), 11q13.4 (rs3824999, intronic to POLD3; P = 3.65 × 10(-10)) and Xp22.2 (rs5934683, near SHROOM2; P = 7.30 × 10(-10)) This brings the number of independent loci associated with CRC risk to 20 and provides further insight into the genetic architecture of inherited susceptibility to CRC.     

红豆杉科及其相关类群的RAPD分析

红豆杉科Ｔａｘａｃｅａｅ、三尖杉科Ｃｅｐｈａｌｏｔａｘａｃｅａｅ和罗汉松科Ｐｏｄｏｃａｒｐａｃｅａｅ系统学研究一直都存在许多困难和分歧 .目前对 3科的研究主要集中在形态学、细胞学方面[1 ,2 ] ,但有关 3科植物的分子系统学和进化遗传学方面的研究却开展得非常有限 .本文应用ＲＡＰＤ技术对 3科植物的分类与系统发育进行了综合研究 .1　材料与方法1 1　材料　选择罗汉松 (Ｐｏｄｏｃａｒｐｕｓｍａｃｒｏｐｈｙｌｌｕｓ)、红豆杉 (Ｔａｘｕｓｃｈｉｎｅｎｓｉｓ)、南方红豆杉 (Ｔａｘｕｓｃｈｉｎｅｎｓｉｓｖａｒ .ｍａｉｒｅｉ)…     

湖北八角莲属（小檗科）一新种

报道湖北省利川县小檗科八角莲属的一种新——利川八角莲     

红豆杉科及相关类群叶绿体rbcL基因与trnL-trnF间隔区序列的分支分析

运用对PCR产物克隆后测序和对PCR产物直接测序的方法对红豆杉科，三尖杉科和罗汉松科16种植物的叶绿体rbcL基因和trnL-trnF基因间隔区序列进行了测定，选用PAUP软件分别对rbcL基因，trnL-trnF间隔区和rbcL基因－trnL-trnF间隔区联合数据矩阵进行分支分析，结果：（1）穗花杉属以置于红豆杉科内为宜，将穗花杉属独立成科的意见未得到支持；（2）三尖杉属内篦子三尖杉地位特殊，赞同成立篦子三尖杉组；（3）罗汉松科属单系群，竹柏类应归属罗汉松，不同意将其从该科中分离出来成立新科竹柏科；（4）不支持红豆杉科独立成目，其单生单轴球果可能是由复合双轴球果减化而来。     

DNA Extraction and RAPD Analysis of Podocarpus

以鸡毛松（Ｐ．ｉｍｂｒｉｃａｔｕｓ．）、竹柏（Ｐ．ｎａｇｉ）、长叶竹柏（Ｐ．ｆｌｅｕｒｙｉ）、百日青（Ｐ．ｎｅｒｉｆｏｌｉｕｓ）和罗汉松（Ｐ．ｍａｃｒｏｐｈｙｌｕｓ）为材料,通过对ＣＴＡＢ法进行改进提取了罗汉松属植物的ＤＮＡ．ＤＮＡ的产率和质量均较理想,能满足ＰＣＲ扩增的需要．对４组８０个引物进行筛选,发现９个引物的带型清晰并呈多态性,每个引物扩增的ＤＮＡ片段数为１～１１个．该９个引物在每个样本中扩增的片段总数平均为３１个．采用ＵＰＧＭＡ法对由ＲＡＰＤ数据求出的遗传距离进行聚类分析,得到的结果显示：本研究中的植物明显地分为３个亚类群,支持在罗汉松属内建立罗汉松组、竹柏组和鸡毛松组的处理方式;不同意把竹柏类从罗汉松属中分离出去成立新科的观点．     

南方红豆杉紫杉烷7β-羟基化酶基因全长序列的克隆和进化分析

 从南方红豆杉Taxus wallichiana var.mairei的新鲜嫩叶中提取基因组DNA作为模板,利用三组特异引物进行PCR扩增,然后克隆测序得到紫杉烷7β-羟基化酶的基因全长。该基因编码区起始密码子为ATG,终止密码子为TGA,全长1 692 bp;碱基组成为490 A (29.0%),351 C (20.7%),362 G (21.4%)和489 T (28.9%)。将紫杉烷7β-羟基化酶基因全长序列与细胞色素P450基因家族的其它三个成员进行比对,发现它与紫杉烷2α-羟基化酶基因、紫杉烷10β-羟基化酶基因及紫杉烷13α-羟基化酶基因的一致性分别为74%、68%及76%。它们的外显子和内含子的连接区均具保守的GT-AG结构,内含子区的变异性明显高于外显子区。进一步以红豆杉属的13个紫杉烷羟基化酶基因家族成员为对象,利用位点间可变ω(非同义替换率dN和同义替换率dS的比值) 模型对该基因家族的适应性进化进行分析。分支模型、位点模型以及分支－位点模型的分析表明：紫杉烷羟基化酶基因家族的少数分支处于正选择压力下(ω>1),但未检测到正选择位点;而绝大部分位点受强烈的负选择作用(ω<1)。     

Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain

Interleukin-12 (IL-12) is a heterodimeric molecule composed of p35 and p40 subunits. Analyses in vitro have defined IL-12 as an important factor for the differentiation of naive T cells into T-helper type 1 CD4+ lymphocytes secreting interferon-gamma (refs 1, 2). Similarly, numerous studies have concluded that IL-12 is essential for T-cell-dependent immune and inflammatory responses in vivo, primarily through the use of IL-12 p40 gene-targeted mice and neutralizing antibodies against p40. The cytokine IL-23, which comprises the p40 subunit of IL-12 but a different p19 subunit, is produced predominantly by macrophages and dendritic cells, and shows activity on memory T cells. Evidence from studies of IL-23 receptor expression and IL-23 overexpression in transgenic mice suggest, however, that IL-23 may also affect macrophage function directly. Here we show, by using gene-targeted mice lacking only IL-23 and cytokine replacement studies, that the perceived central role for IL-12 in autoimmune inflammation, specifically in the brain, has been misinterpreted and that IL-23, and not IL-12, is the critical factor in this response. In addition, we show that IL-23, unlike IL-12, acts more broadly as an end-stage effector cytokine through direct actions on macrophages.