Revising mtDNA haplotypes of the ancient Hungarian conquerors with next generation sequencing

Neparáczki, Endre; Kocsy, Klaudia; Tóth, Gábor Endre; Maróti, Zoltán; Kalmár, Tibor; Bihari, Péter; Nagy, István; Paragh, György; Molnár, Erika; Raskó, István; Török, Tibor

doi:10.1371/journal.pone.0174886

Cited by 38 publications

(53 citation statements)

References 37 publications

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“…The m.8344A > G mutation is particularly interesting as this is for this mutation, one from a disease report and three from population studies, as shown in Table 4 (Kutanan et al, 2018;Mishmar et al, 2003;Neparáczki et al, 2017;Zsurka et al, 2007). Nine individuals from Ovis aries and nine individuals from Pan troglodytes verus harbour this mutation.…”

Section: M8344a > G Mt-trna-lysmentioning

confidence: 99%

What can a comparative genomics approach tell us about the pathogenicity of mtDNA mutations in human populations?

O’Keefe

Lord

Elson

2019

Evolutionary Applications

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Mitochondrial disorders are heterogeneous, showing variable presentation and penetrance. Over the last three decades, our ability to recognize mitochondrial patients and diagnose these mutations, linking genotype to phenotype, has greatly improved. However, it has become increasingly clear that these strides in diagnostics have not benefited all population groups. Recent studies have demonstrated that patients from genetically understudied populations, in particular those of black African heritage, are less likely to receive a diagnosis of mtDNA disease. It has been suggested that haplogroup context might influence the presentation and penetrance of mtDNA disease; thus, the spectrum of mutations that are associated with disease in different populations. However, to date there is only one well‐established example of such an effect: the increased penetrance of two Leber's hereditary optic neuropathy mutations on a haplogroup J background. This paper conducted the most extensive investigation to date into the importance of haplogroup context on the pathogenicity of mtDNA mutations. We searched for proven human point mutations across 726 multiple sequence alignments derived from 33 non‐human species absent of disease. A total of 58 pathogenic point mutations arise in the sequences of these species. We assessed the sequence context and found evidence of population variants that could modulate the phenotypic expression of these point mutations masking the pathogenic effects seen in humans. This supports the theory that sequence context is influential in the presentation of mtDNA disease and has implications for diagnostic practices. We have shown that our current understanding of the pathogenicity of mtDNA point mutations, primarily built on studies of individuals with haplogroups HVUKTJ, will not present a complete picture. This will have the effect of creating a diagnostic inequality, whereby individuals who do not belong to these lineages are less likely to receive a genetic diagnosis.

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Section: M8344a > G Mt-trna-lysmentioning

confidence: 99%

What can a comparative genomics approach tell us about the pathogenicity of mtDNA mutations in human populations?

O’Keefe

Lord

Elson

2019

Evolutionary Applications

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“…Details of the aDNA purification, hybridization capture, sequencing and sequence analysis methods are given in [15]. In order to authenticate the results, we considered the latest recommendations of [25] throughout of the experiments.…”

Section: Ngs Sequencingmentioning

confidence: 99%

“…In most cases Schmutzi measured low contamination levels, however in 12 samples it estimated 99% contamination As in some of these "highly contaminated" samples Schmutzi detected low contamination when it was run with unfiltered BAM files, containing larger number of damaged molecules, we infer that partial UDG treatment in these samples left not enough transitions in key positions for Schmutzi to start with in the first iteration on filtered BAMs. For these samples contamination was estimated traditionally by calculating the proportion of reads which did not correspond to the consensus sequence in diagnostic positions [15]. Sequences were deposited to the European Nucleotide Archive under accession number PRJEB21279.…”

Section: Ngs Sequencingmentioning

confidence: 99%

“…Using the NGS sequencing method combined with target enrichment, we could obtain 102 ancient mitogenome sequences, 78 of which are first reported in this paper, while 24 had been reported in [15]. The 102 sequences belong to 67 sub-Hg-s, and first we elucidated the phylogenetic relations of each Hg-s using M-J Networks as shown in S1 Figure. With a few exceptions M-J networks typically separated neighboring sub-Hg-s to different branches.…”

Section: Phylogenetic Studymentioning

confidence: 99%

“…It is notable that in the latest studies [12,13] population genetic analysis also indicated considerable Central Asian affinity of the Conquerors. However all these studies applied low resolution, error prone PCR based aDNA methods [15] and high resolution Next Generation Sequencing (NGS) data from the Conquerors has not been available yet, though power of discrimination of the entire mitochondrial genome over the hypervariable regions (HVR) has been shown to be huge [16].…”

Section: Introductionmentioning

confidence: 99%

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Mitogenomic data indicate admixture components of Asian Hun and Srubnaya origin in the Hungarian Conquerors

Neparáczki

Maróti

Kalmár

et al. 2018

Preprint

Self Cite

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Endre Neparáczki and Zoltán Maróti contributed equally to this study. Key words:ancient DNA, early Hungarian, next generation sequencing, hybridization capture, Shared Haplogroup Distance, Mitomix AbstractIt has been widely accepted that the Finno-Ugric Hungarian language, originated from proto Uralic people, was brought into the Carpathian Basin by the Hungarian Conquerors. From the middle of the 19 th century this view prevailed against the deep-rooted Hungarian Hun tradition, maintained in folk memory as well as in Hungarian and foreign written medieval sources, which claimed that Hungarians were kinsfolk of the Huns. In order to shed light on the genetic origin of the Conquerors we sequenced 102 mitogenomes from early Conqueror cemeteries and compared them to sequences of all available databases. We applied novel population genetic algorithms, named Shared Haplogroup Distance and MITOMIX, to reveal past admixture of maternal lineages. Phylogenetic and population genetic analysis indicated that more than one third of the Conqueror maternal lineages were derived from Central-Inner Asia and their most probable ultimate sources were the Asian Huns. The rest of the lineages most likely originated from the Bronze Age PotapovkaPoltavka-Srubnaya cultures of the Pontic-Caspian steppe, which area was part of the later European Hun empire. Our data give support to the Hungarian Hun tradition and provides indirect evidence for the genetic connection between Asian and European Huns.

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Whole mitochondrial genome diversity in two Hungarian populations

et al. 2018

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Complete mitochondrial genomics is an effective tool for studying the demographic history of human populations, but there is still a deficit of mitogenomic data in European populations. In this paper, we present results of study of variability of 80 complete mitochondrial genomes in two Hungarian populations from eastern part of Hungary (Szeged and Debrecen areas). The genetic diversity of Hungarian mitogenomes is remarkably high, reaching 99.9% in a combined sample. According to the analysis of molecular variance (AMOVA), European populations showed a low, but statistically significant level of between-population differentiation (Fst = 0.61%, p = 0), and two Hungarian populations demonstrate lack of between-population differences. Phylogeographic analysis allowed us to identify 71 different mtDNA sub-clades in Hungarians, sixteen of which are novel. Analysis of ancestry-informative mtDNA sub-clades revealed a complex genetic structure associated with the genetic impact of populations from different parts of Eurasia, though the contribution from European populations is the most pronounced. At least 8% of ancestry-informative haplotypes found in Hungarians demonstrate similarity with East and West Slavic populations (sub-clades H1c23a, H2a1c1, J2b1a6, T2b25a1, U4a2e, K1c1j, and I1a1c), while the influence of Siberian populations is not so noticeable (sub-clades A12a, C4a1a, and probably U4b1a4).

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Revising mtDNA haplotypes of the ancient Hungarian conquerors with next generation sequencing

Cited by 38 publications

References 37 publications

What can a comparative genomics approach tell us about the pathogenicity of mtDNA mutations in human populations?

What can a comparative genomics approach tell us about the pathogenicity of mtDNA mutations in human populations?

Mitogenomic data indicate admixture components of Asian Hun and Srubnaya origin in the Hungarian Conquerors

Whole mitochondrial genome diversity in two Hungarian populations

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