MitoIMP: A Computational Framework for Imputation of Missing Data in Low-Coverage Human Mitochondrial Genome

The incompleteness of partial human mitochondrial genome sequences makes it difficult to perform relevant comparisons among multiple resources. To deal with this issue, we propose a computational framework for deducing missing nucleotides in the human mitochondrial genome. We applied it to worldwide mitochondrial haplogroup lineages and assessed its performance. Our approach can deduce the missing nucleotides with a precision of 0.99 or higher in most human mitochondrial DNA lineages. Furthermore, although low-coverage mitochondrial genome sequences often lead to a blurred relationship in the multidimensional scaling analysis, our approach can correct this positional arrangement according to the corresponding mitochondrial DNA lineages. Therefore, our framework will provide a practical solution to compensate for the lack of genome coverage in partial and fragmented human mitochondrial genome sequences. In this study, we developed an open-source computer program, MitoIMP, implementing our imputation procedure. MitoIMP is freely available from https://github.com/omics-tools/mitoimp .

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Full mitochondrial genome sequences of two endemic Philippine hornbill species (Aves: Bucerotidae) provide evidence for pervasive mitochondrial DNA recombination

BMC Genomics ◽

10.1186/1471-2164-12-35 ◽

2011 ◽

Vol 12 (1) ◽

Cited By ~ 44

Author(s):

Svenja Sammler ◽

Christoph Bleidorn ◽

Ralph Tiedemann

Keyword(s):

Mitochondrial Dna ◽

Mitochondrial Genome ◽

Dna Recombination ◽

Genome Sequences ◽

Mitochondrial Dna Recombination

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Germline selection shapes human mitochondrial DNA diversity

Science ◽

10.1126/science.aau6520 ◽

2019 ◽

Vol 364 (6442) ◽

pp. eaau6520 ◽

Cited By ~ 62

Author(s):

Wei Wei ◽

Salih Tuna ◽

Michael J. Keogh ◽

Katherine R. Smith ◽

Timothy J. Aitman ◽

...

Keyword(s):

Mitochondrial Dna ◽

Mitochondrial Genome ◽

Germ Line ◽

Population Level ◽

Maternal Transmission ◽

Human Mitochondrial Dna ◽

Genetic Lineages ◽

Selective Forces ◽

Female Germ Line ◽

Genomic Regions

Approximately 2.4% of the human mitochondrial DNA (mtDNA) genome exhibits common homoplasmic genetic variation. We analyzed 12,975 whole-genome sequences to show that 45.1% of individuals from 1526 mother–offspring pairs harbor a mixed population of mtDNA (heteroplasmy), but the propensity for maternal transmission differs across the mitochondrial genome. Over one generation, we observed selection both for and against variants in specific genomic regions; known variants were more likely to be transmitted than previously unknown variants. However, new heteroplasmies were more likely to match the nuclear genetic ancestry as opposed to the ancestry of the mitochondrial genome on which the mutations occurred, validating our findings in 40,325 individuals. Thus, human mtDNA at the population level is shaped by selective forces within the female germ line under nuclear genetic control, which ensures consistency between the two independent genetic lineages.

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SMART: Statistical Mitogenome Assembly with Repeats

10.1101/795633 ◽

2019 ◽

Author(s):

Fahad Alqahtani ◽

Ion I. Măndoiu

Keyword(s):

Mitochondrial Genome ◽

De Novo ◽

Complete Mitochondrial Genome ◽

Bootstrap Support ◽

Mitochondrial Genomes ◽

Genome Sequences ◽

Genome Database ◽

Sequencing Technologies ◽

Likelihood Model ◽

Low Coverage

AbstractBy using next-generation sequencing technologies it is possible to quickly and inexpensively generate large numbers of relatively short reads from both the nuclear and mitochondrial DNA contained in a biological sample. Unfortunately, assembling such whole-genome sequencing (WGS) data with standard de novo assemblers often fails to generate high quality mitochondrial genome sequences due to the large difference in copy number (and hence sequencing depth) between the mitochondrial and nuclear genomes. Assembly of complete mitochondrial genome sequences is further complicated by the fact that many de novo assemblers are not designed for circular genomes, and by the presence of repeats in the mitochondrial genomes of some species.In this paper we describe the Statistical Mitogenome Assembly with Repeats (SMART) pipeline for automated assembly of complete circular mitochondrial genomes from WGS data. SMART uses an efficient coverage-based filter to first select a subset of reads enriched in mtDNA sequences. Contigs produced by an initial assembly step are filtered using BLAST searches against a comprehensive mitochondrial genome database, and used as “baits” for an alignment-based filter that produces the set of reads used in a second de novo assembly and scaffolding step. In the presence of repeats, the possible paths through the assembly graph are evaluated using a maximum-likelihood model. Additionally, the assembly process is repeated a user-specified number of times on re-sampled subsets of reads to select for annotation the reconstructed sequences with highest bootstrap support.Experiments on WGS datasets from a variety of species show that the SMART pipeline produces complete circular mitochondrial genome sequences with a higher success rate than current state-of-the art tools, even from low coverage WGS data. The pipeline is available through an easy-to-use web interface at https://neo.engr.uconn.edu/?tool_id=SMART.

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Comparison of the complete mtDNA genome sequences of human cell lines – HL-60 and GM10742A – from individuals with pro-myelocytic leukemia and leber hereditary optic neuropathy, respectively, and the inclusion of HL-60 in the NIST human mitochondrial DNA standard reference material – SRM 2392-I

Mitochondrion ◽

10.1016/s1567-7249(03)00010-2 ◽

2003 ◽

Vol 2 (6) ◽

pp. 387-400 ◽

Cited By ~ 16

Author(s):

Barbara C. Levin ◽

Koren A. Holland ◽

Diane K. Hancock ◽

Michael Coble ◽

Thomas J. Parsons ◽

...

Keyword(s):

Mitochondrial Dna ◽

Reference Material ◽

Human Cell ◽

Human Cell Lines ◽

Genome Sequences ◽

Leber Hereditary Optic Neuropathy ◽

Human Mitochondrial Dna ◽

Myelocytic Leukemia ◽

Hereditary Optic Neuropathy ◽

Complete Mtdna

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Experimental Strategies Towards Treating Mitochondrial DNA Disorders

Bioscience Reports ◽

10.1007/s10540-007-9042-3 ◽

2007 ◽

Vol 27 (1-3) ◽

pp. 139-150 ◽

Cited By ~ 18

Author(s):

Julie L. Gardner ◽

Lyndsey Craven ◽

Douglass M. Turnbull ◽

Robert W. Taylor

Keyword(s):

Mitochondrial Dna ◽

Mitochondrial Genome ◽

Exercise Training ◽

Disease Transmission ◽

Mitochondrial Respiratory Chain ◽

Mitochondrial Genetics ◽

Molecular Defects ◽

Extensive Range ◽

Experimental Strategies ◽

Human Mitochondrial Genome

An extensive range of molecular defects have been identified in the human mitochondrial genome (mtDNA), causing a range of clinical phenotypes characterized by mitochondrial respiratory chain dysfunction. Sadly, given the complexities of mitochondrial genetics, there are no available cures for mtDNA disorders. In this review, we consider experimental, genetic-based strategies that have been or are being explored towards developing treatments, focussing on two specific areas which we are actively pursuing—assessing the benefit of exercise training for patients with mtDNA defects, and the prevention of mtDNA disease transmission.

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