MitoBamAnnotator: A web-based tool for detecting and annotating heteroplasmy in human mitochondrial DNA sequences

Zhidkov, Ilia; Nagar, Tal; Mo, Dan; Rubin, Eitan

doi:10.1016/j.mito.2011.08.005

Cited by 28 publications

(27 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Samples were mapped to the mtDNA genome and filtered as above. BAM files were analyzed with the online tool MitoBamAnnotator48 (Supplementary Methods). Haplogroups were obtained with Haplogrep49 based on the build 15 phylogeny of PhyloTree50 (Supplementary Table 12).…”

Section: Methodsmentioning

confidence: 99%

Genome flux and stasis in a five millennium transect of European prehistory

et al. 2014

View full text Add to dashboard Cite

The Great Hungarian Plain was a crossroads of cultural transformations that have shaped European prehistory. Here we analyse a 5,000-year transect of human genomes, sampled from petrous bones giving consistently excellent endogenous DNA yields, from 13 Hungarian Neolithic, Copper, Bronze and Iron Age burials including two to high (~22 × ) and seven to ~1 × coverage, to investigate the impact of these on Europe’s genetic landscape. These data suggest genomic shifts with the advent of the Neolithic, Bronze and Iron Ages, with interleaved periods of genome stability. The earliest Neolithic context genome shows a European hunter-gatherer genetic signature and a restricted ancestral population size, suggesting direct contact between cultures after the arrival of the first farmers into Europe. The latest, Iron Age, sample reveals an eastern genomic influence concordant with introduced Steppe burial rites. We observe transition towards lighter pigmentation and surprisingly, no Neolithic presence of lactase persistence.

show abstract

Section: Methodsmentioning

confidence: 99%

Genome flux and stasis in a five millennium transect of European prehistory

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Using MitoBAM-Annotator (Zhidkov et al 2011), the number of reads in each position was counted. Hypersensitivity sites were identified using an algorithm that was recently proved successful for the identification of such sites in human mtDNA (Mercer et al 2011) with the following specific parameters: Briefly, for each position in the mtDNA, an F score was calculated in sliding read windows of 20 bp, a value corresponding to the median of the previously used window size (Mercer et al 2011).…”

Section: Methodsmentioning

confidence: 99%

Transcription Factors Bind Negatively Selected Sites within Human mtDNA Genes

Blumberg

Sailaja

Kundaje

et al. 2014

Genome Biology and Evolution

Self Cite

View full text Add to dashboard Cite

Transcription of mitochondrial DNA (mtDNA)-encoded genes is thought to be regulated by a handful of dedicated transcription factors (TFs), suggesting that mtDNA genes are separately regulated from the nucleus. However, several TFs, with known nuclear activities, were found to bind mtDNA and regulate mitochondrial transcription. Additionally, mtDNA transcriptional regulatory elements, which were proved important in vitro, were harbored by a deletion that normally segregated among healthy individuals. Hence, mtDNA transcriptional regulation is more complex than once thought. Here, by analyzing ENCODE chromatin immunoprecipitation sequencing (ChIP-seq) data, we identified strong binding sites of three bona fide nuclear TFs (c-Jun, Jun-D, and CEBPb) within human mtDNA protein-coding genes. We validated the binding of two TFs by ChIP-quantitative polymerase chain reaction (c-Jun and Jun-D) and showed their mitochondrial localization by electron microscopy and subcellular fractionation. As a step toward investigating the functionality of these TF-binding sites (TFBS), we assessed signatures of selection. By analyzing 9,868 human mtDNA sequences encompassing all major global populations, we recorded genetic variants in tips and nodes of mtDNA phylogeny within the TFBS. We next calculated the effects of variants on binding motif prediction scores. Finally, the mtDNA variation pattern in predicted TFBS, occurring within ChIP-seq negative-binding sites, was compared with ChIP-seq positive-TFBS (CPR). Motifs within CPRs of c-Jun, Jun-D, and CEBPb harbored either only tip variants or their nodal variants retained high motif prediction scores. This reflects negative selection within mtDNA CPRs, thus supporting their functionality. Hence, human mtDNA-coding sequences may have dual roles, namely coding for genes yet possibly also possessing regulatory potential.

show abstract

“…Using SAMtools, the mitochondrial reads were extracted from the BAM files and analyzed with the online tool MitoBamAnnotator [51].…”

Section: Mitochondrial Genome Analysis Via Next Generation Sequencingmentioning

confidence: 99%

Altered Levels of Mitochondrial DNA Are Associated With Female Age, Aneuploidy, and Provide an Independent Measure of Embryonic Implantation Potential

Fragouli

Spath

Alfarawati

et al. 2016

Obstetrical &Amp; Gynecological Survey

View full text Add to dashboard Cite

Mitochondria play a vital role in embryo development. They are the principal site of energy production and have various other critical cellular functions. Despite the importance of this organelle, little is known about the extent of variation in mitochondrial DNA (mtDNA) between individual human embryos prior to implantation. This study investigated the biological and clinical relevance of the quantity of mtDNA in 379 embryos. These were examined via a combination of microarray comparative genomic hybridisation (aCGH), quantitative PCR and next generation sequencing (NGS), providing information on chromosomal status, amount of mtDNA, and presence of mutations in the mitochondrial genome. The quantity of mtDNA was significantly higher in embryos from older women (P=0.003). Additionally, mtDNA levels were elevated in aneuploid embryos, independent of age (P=0.025). Assessment of clinical outcomes after transfer of euploid embryos to the uterus revealed that blastocysts that successfully implanted tended to contain lower mtDNA quantities than those failing to implant (P=0.007). Importantly, an mtDNA quantity threshold was established, above which implantation was never observed. Subsequently, the predictive value of this threshold was confirmed in an independent blinded prospective study, indicating that abnormal mtDNA levels are present in 30% of non-implanting euploid embryos, but are not seen in embryos forming a viable pregnancy. NGS did not reveal any increase in mutation in blastocysts with elevated mtDNA levels. The results of this study suggest that increased mtDNA may be related to elevated metabolism and are associated with reduced viability, a possibility consistent with the 'quiet embryo' hypothesis. Importantly, the findings suggest a potential role for mitochondria in female reproductive aging and the genesis of aneuploidy. Of clinical significance, we propose that mtDNA content represents a novel biomarker with potential value for in vitro fertilisation (IVF) treatment, revealing chromosomally normal blastocysts incapable of producing a viable pregnancy. Data Availability Statement: All relevant data are within the paper and its Supporting Information files.Funding: DW is supported by the NIHR Biomedical Research Centre Oxford. This study was funded by Reprogenetics UK. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Competing Interests: EF, SA and DW are employees of Reprogenetics UK. This does not alter our adherence to all PLOS Genetics policies in Author SummaryMitochondria are small membrane-enclosed structures and are found inside the cells of the body. Mitochondria actively participate in cellular life, and their main function is to generate energy which is used by the cell. For this reason mitochondria are considered as the powerhouses of cells. Unlike other cellular organelles, mitochondria contain their own DNA (mtDNA). MtDNA carries important genetic information concerning cellular metabolism and the gener...

show abstract

MitoBamAnnotator: A web-based tool for detecting and annotating heteroplasmy in human mitochondrial DNA sequences

Cited by 28 publications

References 16 publications

Genome flux and stasis in a five millennium transect of European prehistory

Genome flux and stasis in a five millennium transect of European prehistory

Transcription Factors Bind Negatively Selected Sites within Human mtDNA Genes

Altered Levels of Mitochondrial DNA Are Associated With Female Age, Aneuploidy, and Provide an Independent Measure of Embryonic Implantation Potential

Contact Info

Product

Resources

About