mtDNA Variation and Analysis Using Mitomap and Mitomaster

Abstract

The Mitomap database of human mitochondrial DNA (mtDNA) information has been an important compilation of mtDNA variation for researchers, clinicians, and genetic counselors for the past 25 years. The Mitomap protocol shows how users may look up human mitochondrial gene loci, search for public mitochondrial sequences, and browse or search for reported general population nucleotide variants as well as those reported in clinical disease. Within Mitomap is the powerful sequence analysis tool for human mitochondrial DNA, Mitomaster. The Mitomaster protocol gives step‐by‐step instructions showing how to submit sequences to identify nucleotide variants relative to the rCRS, determine the haplogroup, and view species conservation. User‐supplied sequences, GenBank identifiers, and single‐nucleotide variants may be analyzed. Curr. Protoc. Bioinform. 44:1.23.1‐1.23.26. © 2013 by John Wiley & Sons, Inc.

NSUN 3 and ABH 1 modify the wobble position of mt‐t RNA Met to expand codon recognition in mitochondrial translation

“…Our finding that the mt‐tRNA Met C39U mutation, which has previously been identified in patients with mitochondrial dysfunction (Lott et al , 2013; Tang et al , 2013), largely abolishes m 5 C34 formation by NSUN3, suggests that the C34 modification is required for mt‐tRNA Met function in vivo and that mt‐tRNA Met malfunction might cause the disease in these patients. To analyse the requirement for the modifications installed by NSUN3 and ABH1 for translation in mitochondria, we measured the amount of 35 S‐methionine incorporated into proteins during mitochondrial translation in vivo after depletion of NSUN3 or ABH1.…”

“…These modifications modulate codon–anticodon basepairing, often allowing one tRNA to recognise several different nucleosides in the third position of the codon. Mutations in enzymes responsible for introducing these “wobble base” modifications or genetic alterations in tRNA sequences that affect such modifications are often associated with disease, especially in mitochondrial tRNAs (Lott et al , 2013; Powell et al , 2015). …”

Recent Advances in Mitochondrial Disease

“…The first pathogenic mtDNA mutations were reported in 1988 (41,97); since then, an increasing number of mtDNA mutations associated with a wide variety of clinical symptoms have been identified in patients with mitochondrial disease. To date, more than 260 different pathogenic mutations have been characterized [see MITOMAP (59)], and the number continues to rise (52,64). These mutations can be classified into three types: point mutations in protein-coding genes, point mutations in genes involved in protein synthesis (tRNA or rRNA genes), and mtDNA rearrangements, including mtDNA deletions and insertions.…”

Bridging two scholarly islands enriches both: COI DNA barcodes for species identification versus human mitochondrial variation for the study of migrations and pathologies

“…2004; Lott et al. 2013). In most of the recent human mitochondrial studies, the entire genome is sequenced.…”