Genetic analyses of Highly conserved Conserved noncoding sequences in vertebrates

脊椎动物高度保守的保守非编码序列的遗传分析

• 批准号: 18570008
• 负责人: SAKURABA Yoshiyuki
• 金额: $ 2.53万
• 依托单位: The Institute of Physical and Chemical Research
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18570008/
• 关键词: noncoding; conserved sequences; Orvzias latipes; vertebrates; genome; DNA

Comparative sequence analyses have identified highly conserved genomic DNA sequences, including noncoding sequences, between humans and other species. By performing whole-genome comparisons of human and mouse, we have identified 611 conserved noncoding sequences longer than 500 by with more than 95% identity between the species. The LCNS were distributed throughout the genome except for the Y chromosome and often occurred in clusters within regions with a low-density of coding genes. Many of the LCNS were also highly conserved in other mammals, chickens, frogs, and fish ; however, we were unable to fmd orthologous sequences in the genomes of invertebrate species. In order to examine whether these conserved sequences are functionally important or merely mutational cold spots, we directly measured the frequencies of ENU-induced germline mutations in the LCNS of the mouse. The mutation frequencies were equivalent to those found in other genomic regions, including coding sequences and introns, suggesting that the LCNS are not mutational cold spots at all. Taken together, these results suggest that mutations occur with equal frequency in LCNS but are eliminated by natural selection during the course of evolution.We screened ENU-induced mutations in Medaka genomic DNA library by Temperature Gradient Capillary Electrophoresis method. From total 19, 444, 664 by screening, we found 46 mutations in 9 LCNS in Medaka.

比较序列分析已经确定了人类和其他物种之间高度保守的基因组DNA序列，包括非编码序列。通过对人类和小鼠的全基因组进行比较，我们发现了611个长度超过500 bp的保守非编码序列，这些序列在物种之间的同源性超过95%。LCNS分布于除Y染色体外的整个基因组中，并且通常在编码基因密度低的区域内成簇出现。许多LCNS在其他哺乳动物、鸡、青蛙和鱼中也高度保守;然而，我们无法在无脊椎动物的基因组中找到直向序列。为了检查这些保守序列是否在功能上重要或仅仅是突变冷点，我们直接测量了小鼠LCNS中ENU诱导的种系突变的频率。突变频率与其他基因组区域（包括编码序列和内含子）中发现的突变频率相当，表明LCNS根本不是突变冷点。这些结果表明，在LCNS中，突变发生的频率相同，但在进化过程中被自然选择所消除。在筛选的19444664个样本中，我们在9个青鳉LCNS中发现了46个突变。

项目成果

体系的なマウス突然変異体開発プロジェクト(2007-10) : Gene-driven mutagenesisの概要

系统性小鼠突变体开发项目（2007-10）：基因驱动诱变概述

• 发表时间: 2007
• 作者: Kamei;Y;Masuya H.;Masuya H.;Abe T.;Taniguch Y.;Abe T;Taniguch Y.;Abe T.;Sakuraba Y.;Sakuraba Y.;櫻庭喜行
• 通讯作者: 櫻庭喜行

Long Conserved Noncoding Sequences(LCNS)

长保守非编码序列（LCNS）

• 发表时间: 2006
• 作者: Kamei;Y;Masuya H.;Masuya H.;Abe T.;Taniguch Y.;Abe T;Taniguch Y.;Abe T.;Sakuraba Y.;Sakuraba Y.;櫻庭喜行;Sakuraba Y;櫻庭 喜行;Sakuraba Y.
• 通讯作者: Sakuraba Y.

Generation of medaka gene knockout models by target-selected mutagenesis.

• DOI: 10.1186/gb-2006-7-12-r116
• 发表时间: 2006
• 期刊: Genome biology
• 影响因子: 12.3
• 作者: Taniguchi Y;Takeda S;Furutani-Seiki M;Kamei Y;Todo T;Sasado T;Deguchi T;Kondoh H;Mudde J;Yamazoe M;Hidaka M;Mitani H;Toyoda A;Sakaki Y;Plasterk RH;Cuppen E
• 通讯作者: Cuppen E

Mutational pattern and frequency of induced nucleotide changes in mouse ENU mutagenesis.

小鼠ENU诱变中诱导核苷酸变化的突变模式和频率。

• DOI: 10.1186/1471-2199-8-52
• 发表时间: 2007-06-20
• 期刊: BMC molecular biology
• 作者: Takahasi KR;Sakuraba Y;Gondo Y
• 通讯作者: Gondo Y

高度保存noncodingゲノム配列(LCNS)は突然変異のcold spotではない

高度保守的非编码基因组序列 (LCNS) 不是突变的冷点

• 发表时间: 2006
• 作者: Kamei;Y;Masuya H.;Masuya H.;Abe T.;Taniguch Y.;Abe T;Taniguch Y.;Abe T.;Sakuraba Y.;Sakuraba Y.;櫻庭喜行;Sakuraba Y;櫻庭 喜行;Sakuraba Y.;Sakuraba Y;T Kimura;櫻庭喜行
• 通讯作者: 櫻庭喜行