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腾讯登录Nat Genet：科学家发现增加脑瘤风险新的遗传突变
| 导读 | 近日，来自加利福尼亚大学梅奥诊所的研究者通过研究发现，在遗传密码的特殊位置携带碱基“G”的人群患特定类型的脑瘤风险是携带碱基“A”的人群的6倍以上。这项研究成果刊登在了8月26日的国际著名杂志<em>Nature Genetics</em>上。这项研究成果可以帮助研究者快速发现患有特定神经胶质瘤的患者，以利于对患者进行早期诊断和治疗。
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近日，来自加利福尼亚大学梅奥诊所的研究者通过研究发现，在遗传密码的特殊位置携带碱基“G”的人群患特定类型的脑瘤风险是携带碱基“A”的人群的6倍以上。这项研究成果刊登在了8月26日的国际著名杂志<em>Nature Genetics</em>上。这项研究成果可以帮助研究者快速发现患有特定神经胶质瘤的患者，以利于对患者进行早期诊断和治疗。
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研究者想确定这种特定位点的碱基置换是否是脑瘤的主要发病原因。基于研究发现，研究者认为临床检验可以确定病人所患的脑瘤类型。数年之前，研究者试图去寻找和神经胶质瘤发展相关的基因组区域，最终研究者发现8号染色体的部分包含的单核苷酸多态性或者SNPs和脑瘤直接相关。从那时候开始，研究者Jenkins便和同事使用一种复杂的基因组技术来寻找引发脑瘤形成的特定SNP。
通过大量的摸索试验，研究者发现了一种SNP，称为rs55705857（乳腺癌相关基因）也和神经胶质瘤的发病相关，研究者在这个SNP上发现的是更多的“G”鸟嘌呤，而不是“A”腺嘌呤，其和神经胶质瘤的缓慢发展直接相关。
与此同时，研究者也比对了哺乳动物进化过程中的基因突变序列的差异性，发现这种突变早在鸭嘴兽中已经存在了。计算机模型分析揭示了这种突变的区域或许是一种microRNA，microRNA是一种特殊的核酸序列，可以控制细胞中遗传信使的活性。结果显示SNP携带有部分的microRNA功能，而且碱基从A到G的突变会带来明显的后果。研究者目前正在研究是否microRNA真正存在，而且其功能是如何的？
研究者Jenkins表示，改变的microRNA或许以肿瘤抑制基因为靶点，其或许可以激活癌基因，也可以调节基因组的稳定性。目前对于基因组新纪元的最大的挑战就是如何赋予突变基因新的功能。（生物谷Bioon.com）
编译自：<a title="" href="http://www.sciencedaily.com/releases/2012/08/120826143354.htm" target="_blank">Genomic Variant That Increases Risk of Brain Tumors Discovered</a>
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<a title="" href="http://dx.doi.org/doi:10.1038/ng.2388" target="_blank">doi:10.1038/ng.2388</a>
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<br/><strong>A low-frequency variant at 8q24.21 is strongly associated with risk of oligodendroglial tumors and astrocytomas with IDH1 or IDH2 mutation </strong><br/>
Robert B Jenkins,1, 12 Yuanyuan Xiao,2, 11 Hugues Sicotte,3, 11 Paul A Decker,3, 11 Thomas M Kollmeyer,1, 11 Helen M Hansen,4, 11 Matthew L Kosel,3, 11 Shichun Zheng,4 Kyle M Walsh,4, 5 Terri Rice,4 Paige Bracci,2 Lucie S McCoy,4 Ivan Smirnov,4 Joseph S Patoka,4 George Hsuang,4 Joe L Wiemels,2, 6 Tarik Tihan,7 Alexander R Pico,8 Michael D Prados,4 Susan M Chang,4 Mitchel S Berger,4 Alissa A Caron,1 Stephanie R Fink,1 Chandralekha Halder,1 Amanda L Rynearson,1 Brooke L Fridley,3 Jan C Buckner,9 Brian P O'Neill,10 Caterina Giannini,1 Daniel H Lachance,1, 10 John K Wiencke,4, 6, 12 Jeanette E Eckel-Passow3, 12 & Margaret R Wrensch4, 6, 12 et al.
Variants at 8q24.21 have been shown to be associated with glioma development. By means of tag SNP genotyping and imputation, pooled next-generation sequencing using long-range PCR and subsequent validation SNP genotyping, we identified seven low-frequency SNPs at 8q24.21 that were strongly associated with glioma risk (P = 1 × 10−25 to 1 × 10−14). The most strongly associated SNP, rs55705857, remained highly significant after individual adjustment for the other top six SNPs and two previously published SNPs. After stratifying by histological and tumor genetic subtype, the most significant associations of rs55705857 were with oligodendroglial tumors and gliomas with mutant IDH1 or IDH2 (odds ratio (OR) = 5.1, P = 1.1 × 10−31 and OR = 4.8, P = 6.6 × 10−22, respectively). Strong associations were observed for astrocytomas with mutated IDH1 or IDH2 (grades 2–4) (OR = 5.16–6.66, P = 4.7 × 10−12 to 2.2 × 10−8) but not for astrocytomas with wild-type IDH1 and IDH2 (smallest P = 0.26). The conserved sequence block that includes rs55705857 is consistently modeled as a microRNA.
<br/>来源：生物谷
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研究者想确定这种特定位点的碱基置换是否是脑瘤的主要发病原因。基于研究发现，研究者认为临床检验可以确定病人所患的脑瘤类型。数年之前，研究者试图去寻找和神经胶质瘤发展相关的基因组区域，最终研究者发现8号染色体的部分包含的单核苷酸多态性或者SNPs和脑瘤直接相关。从那时候开始，研究者Jenkins便和同事使用一种复杂的基因组技术来寻找引发脑瘤形成的特定SNP。
通过大量的摸索试验，研究者发现了一种SNP，称为rs55705857（乳腺癌相关基因）也和神经胶质瘤的发病相关，研究者在这个SNP上发现的是更多的“G”鸟嘌呤，而不是“A”腺嘌呤，其和神经胶质瘤的缓慢发展直接相关。
与此同时，研究者也比对了哺乳动物进化过程中的基因突变序列的差异性，发现这种突变早在鸭嘴兽中已经存在了。计算机模型分析揭示了这种突变的区域或许是一种microRNA，microRNA是一种特殊的核酸序列，可以控制细胞中遗传信使的活性。结果显示SNP携带有部分的microRNA功能，而且碱基从A到G的突变会带来明显的后果。研究者目前正在研究是否microRNA真正存在，而且其功能是如何的？
研究者Jenkins表示，改变的microRNA或许以肿瘤抑制基因为靶点，其或许可以激活癌基因，也可以调节基因组的稳定性。目前对于基因组新纪元的最大的挑战就是如何赋予突变基因新的功能。（生物谷Bioon.com）
编译自：<a title="" href="http://www.sciencedaily.com/releases/2012/08/120826143354.htm" target="_blank">Genomic Variant That Increases Risk of Brain Tumors Discovered</a>
<div id="ztload">
<div> </div>
<div>
<div>
<img src="http://www.bioon.com/biology/UploadFiles/201208/2012082722203754.jpg" alt="" width="113" height="149" border="0" />
<a title="" href="http://dx.doi.org/doi:10.1038/ng.2388" target="_blank">doi:10.1038/ng.2388</a>
PMC:
PMID:
</div>
<div>
<br/><strong>A low-frequency variant at 8q24.21 is strongly associated with risk of oligodendroglial tumors and astrocytomas with IDH1 or IDH2 mutation </strong><br/>
Robert B Jenkins,1, 12 Yuanyuan Xiao,2, 11 Hugues Sicotte,3, 11 Paul A Decker,3, 11 Thomas M Kollmeyer,1, 11 Helen M Hansen,4, 11 Matthew L Kosel,3, 11 Shichun Zheng,4 Kyle M Walsh,4, 5 Terri Rice,4 Paige Bracci,2 Lucie S McCoy,4 Ivan Smirnov,4 Joseph S Patoka,4 George Hsuang,4 Joe L Wiemels,2, 6 Tarik Tihan,7 Alexander R Pico,8 Michael D Prados,4 Susan M Chang,4 Mitchel S Berger,4 Alissa A Caron,1 Stephanie R Fink,1 Chandralekha Halder,1 Amanda L Rynearson,1 Brooke L Fridley,3 Jan C Buckner,9 Brian P O'Neill,10 Caterina Giannini,1 Daniel H Lachance,1, 10 John K Wiencke,4, 6, 12 Jeanette E Eckel-Passow3, 12 & Margaret R Wrensch4, 6, 12 et al.
Variants at 8q24.21 have been shown to be associated with glioma development. By means of tag SNP genotyping and imputation, pooled next-generation sequencing using long-range PCR and subsequent validation SNP genotyping, we identified seven low-frequency SNPs at 8q24.21 that were strongly associated with glioma risk (P = 1 × 10−25 to 1 × 10−14). The most strongly associated SNP, rs55705857, remained highly significant after individual adjustment for the other top six SNPs and two previously published SNPs. After stratifying by histological and tumor genetic subtype, the most significant associations of rs55705857 were with oligodendroglial tumors and gliomas with mutant IDH1 or IDH2 (odds ratio (OR) = 5.1, P = 1.1 × 10−31 and OR = 4.8, P = 6.6 × 10−22, respectively). Strong associations were observed for astrocytomas with mutated IDH1 or IDH2 (grades 2–4) (OR = 5.16–6.66, P = 4.7 × 10−12 to 2.2 × 10−8) but not for astrocytomas with wild-type IDH1 and IDH2 (smallest P = 0.26). The conserved sequence block that includes rs55705857 is consistently modeled as a microRNA.
<br/>来源：生物谷
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