生命组学-可遗传变异

GC content:碱基:

transcription-coupled repair|Germ|HK|TS|Mutation|四类变异-LMLPHP

GC content不同的植物对应的gene length,可看作上图的转置:

transcription-coupled repair|Germ|HK|TS|Mutation|四类变异-LMLPHP

由GC content看出来碱基变异程度,可以找到对应碱基改变,所以gene expression也会相应改变,比如亲水到疏水。

转录偶联变异transcription-coupled repair

核苷酸切除修复(nucleotide excision repair)是一种DNA修复方法。[1]由于化学、辐射和很多其他因素的都会对DNA碱基对造成破坏,DNA时常需要修复。核苷酸切除修复是其中一种很重要的方法,通过移除绝大部分紫外线导致的DNA损伤,使得细胞免于受到有害变异的影响(主要形式为胸腺嘧啶二聚体及6,4-光产物)。其发现者,瑞典生物化学家托马斯·林达尔凭此获得2015年诺贝尔化学奖

Housekeeping gene:In molecular biology, housekeeping genes are typically constitutive genes that are required for the maintenance of basic cellular function, and are expressed in all cells of an organism under normal and patho-physiological conditions.

Germ lineage 胚芽系可遗传变异:TCR:transcription coupled repair

Transcription结构:

transcription-coupled repair|Germ|HK|TS|Mutation|四类变异-LMLPHP

Promoter是TATA box;Activator 与enhancer结合

transcription-coupled repair|Germ|HK|TS|Mutation|四类变异-LMLPHP

HK (housekeeping)or TS(condition-related)通过图示来界定基因

transcription-coupled repair|Germ|HK|TS|Mutation|四类变异-LMLPHP

The higher GC and CpG island content may indicate HK promoters are more stable than the TS promoters. HK genes with high density CpG islands have higher transcriptional activity across tissues, that is, it has a higher level of expression, while TS genes may be restricted by strict expression in specific tissue

HK gene有高CpG岛,tissue specific gene 与其相反,可以用于识别肿瘤。

transcription-coupled repair|Germ|HK|TS|Mutation|四类变异-LMLPHP

HK受到选择所以表达有选择有上升(SNP随expression增大而增大),TS gene则没有。

transcription-coupled repair|Germ|HK|TS|Mutation|四类变异-LMLPHP

transcription-coupled repair|Germ|HK|TS|Mutation|四类变异-LMLPHP

想要找到(germ lineage中是否存在HK且恒定的,即element且稳定可控的)gene如何调控-----查看表达和SNP的关系。

Mutation:HK来自TCR及复制期导致error,与TS相比比较少,因为间期一直在被表达。TS来自细胞间期复制导致error,mutation比较多的原因是因为一直没被表达,所以一直暴露在外,error多即变体多。

DNA复制过程中,会产生损伤,所以需要修复,此时转录返回5’原点,所以5’复制多表达多出错也多,即mutation多。DNA错误由聚合酶导致,修复时也需要聚合酶,所以也有错误or损伤。

transcription-coupled repair|Germ|HK|TS|Mutation|四类变异-LMLPHP

四类变异:

结构性序列与基因产物功能性选择原理

transcription-coupled repair|Germ|HK|TS|Mutation|四类变异-LMLPHP

转录偶联原理

复制时间异化原理

transcription-coupled repair|Germ|HK|TS|Mutation|四类变异-LMLPHP

transcription-coupled repair|Germ|HK|TS|Mutation|四类变异-LMLPHP

生殖系与体细胞系共表达原理--HK vs TS

05-11 16:25