title: Large scale mtDNA sequencing reveals sequence and functional conservation as major determinants of homoplasmic mtDNA variant distribution.
abstract: The mitochondrial DNA (mtDNA) is highly variable, containing large numbers of pathogenic mutations and neutral polymorphisms. The spectrum of homoplasmic mtDNA variation was characterized in 730 subjects and compared with known pathogenic sites. The frequency and distribution of variants in protein coding genes were inversely correlated with conservation at the amino acid level. Analysis of tRNA secondary structures indicated a preference of variants for the loops and some acceptor stem positions. This comprehensive overview of mtDNA variants distinguishes between regions and positions which are likely not critical, mainly conserved regions with pathogenic mutations and essential regions containing no mutations at all.
authors.affiliation: Department of Genetics and Cell Biology, Maastricht University, Maastricht, The Netherlands.
authors.forename: A M
authors.initials: AM
authors.lastname: Voets
authors.forename: B J C
authors.initials: BJ
authors.lastname: van den Bosch
authors.forename: A P
authors.initials: AP
authors.lastname: Stassen
authors.forename: A T
authors.initials: AT
authors.lastname: Hendrickx
authors.forename: D M
authors.initials: DM
authors.lastname: Hellebrekers
authors.forename: L
authors.initials: L
authors.lastname: Van Laer
authors.forename: E
authors.initials: E
authors.lastname: Van Eyken
authors.forename: G
authors.initials: G
authors.lastname: Van Camp
authors.forename: A
authors.initials: A
authors.lastname: Pyle
authors.forename: S V
authors.initials: SV
authors.lastname: Baudouin
authors.forename: P F
authors.initials: PF
authors.lastname: Chinnery
authors.forename: H J M
authors.initials: HJ
authors.lastname: Smeets
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D017124:Conserved Sequence; D004272:DNA, Mitochondrial / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D007223:Infant; D008875:Middle Aged; D009690:Nucleic Acid Conformation; D011110:Polymorphism, Genetic; D012343:RNA, Transfer / Q000235:genetics; D017422:Sequence Analysis, DNA; D055815:Young Adult
chemical_list: D004272:DNA, Mitochondrial; D012343:RNA, Transfer