Genomic Mosaicism Formed by Somatic Variation in the Aging and Diseased Brain.
Genomic Mosaicism Formed by Somatic Variation in the Aging and Diseased Brain.
复制标题
DOI：
10.3390/genes12071071
复制
发表时间：
2021-07-14
期刊：
影响因子：
3.5
通讯作者：
Chun J
中科院分区：
文献类型：
--
作者：
Costantino I;Nicodemus J;Chun J
在过去的20年里，对单个脑细胞基因组的分析表明，大脑是由具有无数不同基因组的细胞组成的：大脑是一个基因组嵌合体，由一系列发生在体细胞上且不影响种系的DNA序列改变过程产生。因此，这些序列变化是不可遗传的。有些过程似乎发生在神经发生过程中，此时细胞有丝分裂，而其他过程也可能在有丝分裂后细胞中发挥作用。在这里，我们回顾了现已记录的多种形式的 DNA 序列改变：非整倍体和异体、较小拷贝数变异 (CNV)、体细胞重复扩增、逆转录转座子、与体细胞基因重组 (SGR) 相关的基因组 cDNA (gencDNA) 和单核苷酸变异 (SNV)。 DNA 含量变异（DCV）这个包罗万象的术语也被用来描述整体现象，其中可能包括单个细胞基因组内的多种形式。基因组嵌合分析的一个必要步骤是持续的技术开发，对此也进行了讨论。基因组嵌合体改变了最稳定的生物分子之一——DNA，它可能会产生许多影响，从包括衰老影响在内的正常功能，到神经退行性疾病和其他脑部疾病中发生的功能障碍，其中大多数表现出散发性表现，与因果遗传基因无关。
Over the past 20 years, analyses of single brain cell genomes have revealed that the brain is composed of cells with myriad distinct genomes: the brain is a genomic mosaic, generated by a host of DNA sequence-altering processes that occur somatically and do not affect the germline. As such, these sequence changes are not heritable. Some processes appear to occur during neurogenesis, when cells are mitotic, whereas others may also function in post-mitotic cells. Here, we review multiple forms of DNA sequence alterations that have now been documented: aneuploidies and aneusomies, smaller copy number variations (CNVs), somatic repeat expansions, retrotransposons, genomic cDNAs (gencDNAs) associated with somatic gene recombination (SGR), and single nucleotide variations (SNVs). A catch-all term of DNA content variation (DCV) has also been used to describe the overall phenomenon, which can include multiple forms within a single cell’s genome. A requisite step in the analyses of genomic mosaicism is ongoing technology development, which is also discussed. Genomic mosaicism alters one of the most stable biological molecules, DNA, which may have many repercussions, ranging from normal functions including effects of aging, to creating dysfunction that occurs in neurodegenerative and other brain diseases, most of which show sporadic presentation, unlinked to causal, heritable genes.
登录
查看更多内容
影响因子：
11.2
作者：
Bettencourt C;Hensman-Moss D;Flower M;Wiethoff S;Brice A;Goizet C;Stevanin G;Koutsis G;Karadima G;Panas M;Yescas-Gómez P;García-Velázquez LE;Alonso-Vilatela ME;Lima M;Raposo M;Traynor B;Sweeney M;Wood N;Giunti P;SPATAX Network;Durr A;Holmans P;Houlden H;Tabrizi SJ;Jones L
通讯作者：
Jones L
影响因子：
3.5
作者：
Beck, JA;Poulter, M;Tabrizi, SJ
通讯作者：
Tabrizi, SJ
影响因子：
9.9
作者：
Ahn, T. -B.;Kim, S. Y.;Jeon, B. S.
通讯作者：
Jeon, B. S.
影响因子：
30.8
作者：
ANDREW, SE;GOLDBERG, YP;HAYDEN, MR
通讯作者：
HAYDEN, MR
影响因子：
8.8
作者：
Cai X;Evrony GD;Lehmann HS;Elhosary PC;Mehta BK;Poduri A;Walsh CA
通讯作者：
Walsh CA