The Mighty NUMT: Mitochondrial DNA Flexing Its Code in the Nuclear Genome.
The Mighty NUMT: Mitochondrial DNA Flexing Its Code in the Nuclear Genome.
复制标题
DOI：
10.3390/biom13050753
复制
发表时间：
2023-04-27
期刊：
影响因子：
5.5
通讯作者：
中科院分区：
文献类型：
--
作者：
核-线粒体DNA片段（NUMT）是插入到核基因组中的线粒体DNA（mtDNA）片段。一些NUMT在人群中很常见，但大多数NUMT是罕见的，并且是个体特有的。NUMT的大小范围从24个碱基对到几乎包含整个mtDNA，并且在整个核基因组中发现。新出现的证据表明，NUMT的形成是人类的一个持续过程。NUMT通过引入假阳性变体，特别是以低变体等位基因频率（VAF）存在的异质变体，污染mtDNA的测序结果。在我们的综述中，我们讨论了NUMT在人群中的患病率，通过DNA修复机制从头NUMT插入的潜在机制，并提供了一个概述现有的方法，以尽量减少NUMT污染。除了过滤已知的NUMT外，湿实验室和计算方法都可以用来最大限度地减少人类mtDNA分析中NUMT的污染。目前的办法包括：（1）分离线粒体以富集mtDNA;（2）应用基本局部比对以鉴定NUMT用于后续过滤;（3）用于NUMT检测的生物信息学管道;（4）基于k聚体的NUMT检测;以及（5）通过mtDNA拷贝数、VAF或序列质量评分过滤候选假阳性变体。必须采用多种方法才能有效鉴别样品中的NUMT。尽管下一代测序正在彻底改变我们对异质性线粒体DNA的理解，但它也带来了新的挑战，即高患病率和个体特异性NUMT，在线粒体遗传学研究中需要谨慎处理。
Nuclear-mitochondrial DNA segments (NUMTs) are mitochondrial DNA (mtDNA) fragments that have been inserted into the nuclear genome. Some NUMTs are common within the human population but most NUMTs are rare and specific to individuals. NUMTs range in size from 24 base pairs to encompassing nearly the entire mtDNA and are found throughout the nuclear genome. Emerging evidence suggests that the formation of NUMTs is an ongoing process in humans. NUMTs contaminate sequencing results of the mtDNA by introducing false positive variants, particularly heteroplasmic variants present at a low variant allele frequency (VAF). In our review, we discuss the prevalence of NUMTs in the human population, the potential mechanisms of de novo NUMT insertion via DNA repair mechanisms, and provide an overview of the existing approaches for minimizing NUMT contamination. Apart from filtering known NUMTs, both wet lab-based and computational methods can be used to minimize the contamination of NUMTs in analyses of human mtDNA. Current approaches include: (1) isolating mitochondria to enrich for mtDNA; (2) applying basic local alignment to identify NUMTs for subsequent filtering; (3) bioinformatic pipelines for NUMT detection; (4) k-mer-based NUMT detection; and (5) filtering candidate false positive variants by mtDNA copy number, VAF, or sequence quality score. Multiple approaches must be applied in order to effectively identify NUMTs in samples. Although next-generation sequencing is revolutionizing our understanding of heteroplasmic mtDNA, it also raises new challenges with the high prevalence and individual-specific NUMTs that need to be handled with care in studies of mitochondrial genetics.
登录
查看更多内容
影响因子：
4.5
作者：
Hazkani-Covo E;Covo S
通讯作者：
Covo S
影响因子：
3.7
作者：
Gould MP;Bosworth CM;McMahon S;Grandhi S;Grimberg BT;LaFramboise T
通讯作者：
LaFramboise T
影响因子：
7.8
作者：
Cheng, Xin;Ivessa, Andreas S.
通讯作者：
Ivessa, Andreas S.
DOI：
10.1006/bbrc.1998.8353
发表时间：
1998-03-27
影响因子：
3.1
作者：
Davis, JN;Parker, WD
通讯作者：
Parker, WD
影响因子：
7
作者：
Laricchia KM;Lake NJ;Watts NA;Shand M;Haessly A;Gauthier L;Benjamin D;Banks E;Soto J;Garimella K;Emery J;Genome Aggregation Database Consortium;Rehm HL;MacArthur DG;Tiao G;Lek M;Mootha VK;Calvo SE
通讯作者：
Calvo SE