bims-humivi Biomed News
on Human mito-nuclear genetic interplay
Issue of 2026–08–02
two papers selected by
Mariangela Santorsola, Università di Pavia
  1. Nuclear and Mitochondrial DNA Variants in Chiari Malformation Type 1: Insights from an East Coast Malaysian Cohort.
  2. Evolutionary regimes determine the accuracy of epistasis inference from temporal genetic data.
  1. Eurasian J Med. 2026 Jul 17. 58(4): 1-10
    Nuclear and Mitochondrial DNA Variants in Chiari Malformation Type 1: Insights from an East Coast Malaysian Cohort.
    Siti Nornazihah Mohd Rosdi, Abdul Aziz Mohamed Yusoff.
       BACKGROUND: Chiari malformation type 1 (CM1) is a neurological disorder characterized by cerebellar tonsil herniation. While nuclear DNA has been associated with craniovertebral development, the role of mitochondrial DNA (mtDNA) remains unclear. This study investigated nuclear DNA variants (PAX1, EPAS1, DKK1, GDF6) and mtDNA D-loop mutations in CM1 patients from East Coast Malaysia.
    METHODS: Sixty-eight participants were enrolled, comprising 38 CM1 patients and 30 controls. Genomic DNA from peripheral blood was analyzed by polymerase chain reaction amplification and Sanger sequencing. Associations between genetic variants and clinicopathological parameters (age, sex, tonsillar herniation, syringomyelia) were assessed using chi-square or Fisher's exact test.
    RESULTS: Four nuclear DNA variants were identified, comprising a synonymous PAX1 mutation (c.555G>A, p.K185K) and intronic changes in EPAS1 (c.1035-7C>G), DKK1 (c.548-3T>C), and GDF6 (c.406+112T>C), none of which exhibited significant associations with clinicopathological characteristics. In contrast, mtDNA analysis revealed that 50% of CM1 patients (n = 30) harbored D-loop mutations, predominantly T>C or G>A transitions, including 18 novel variants. Mutation frequency was significantly higher in patients with more severe tonsillar herniation (>10 mm) (OR = 28.570; 95% CI: 3.080-250.000; P < .001) and in those with syringomyelia (OR = 7.792; 95% CI: 1.782-34.060; P = .007), while no significant associations were observed with age or sex.
    CONCLUSION: Nuclear DNA variants may function as genetic modifiers without significant clinical impact. Conversely, mtDNA D-loop mutations were prevalent and correlated with disease severity, suggesting a contributory role in CM1 pathogenesis and warranting further investigation of mitochondrial genetic factors. Cite this article as: Rosdi SNM, Mohamed Yusoff AA. Nuclear and mitochondrial DNA variants in Chiari malformation type 1: insights from an east coast Malaysian cohort. Eurasian J Med. 2026, 58(4), 1209, doi: 10.5152/eurasianjmed.2026.251209.
    DOI:  https://doi.org/10.5152/eurasianjmed.2026.251209
  2. bioRxiv. 2026 Jul 20. pii: 2026.07.16.739011. [Epub ahead of print]
    Evolutionary regimes determine the accuracy of epistasis inference from temporal genetic data.
    Kai S Shimagaki, John P Barton.
      Epistasis, the non-additive effects of mutations, shapes fitness landscapes and evolutionary trajectories. Temporal genetic data reveal evolutionary dynamics and could be used to infer epistatic interactions, especially through linkage disequilibrium (LD) between interacting mutations. However, other evolutionary forces can also generate LD, challenging inference. Here, we systematically evaluated the accuracy of a variety of epistasis inference approaches across a range of selective pressures, recombination rates, and population sizes. In general, we found that inference accuracy depends on the evolutionary regime: methods based on marginal path likelihood (MPL) performed best under strong selection and low recombination, whereas quasi-linkage equilibrium (QLE) approaches were more accurate when recombination is frequent. We further showed that the strength of genetic drift can influence inference accuracy for approaches that learn from changes in allele frequencies over time. Collectively, our results show that the detectability of epistasis from temporal genetic data depends on the interplay between selection, recombination, and genetic drift, providing guidance for method selection across evolutionary contexts.
    DOI:  https://doi.org/10.64898/2026.07.16.739011
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