Search Results (10)

Four types of archaeogenetic data mining are used to investigate the origin of the Minoans and the Uralic peoples: (1) six SNP mutations related to eye, hair, and skin phenotypes; (2) whole-genome admixture analysis using the G25 system; (3) an analysis of the history of the U5 mitochondrial DNA haplogroup; and (4) an analysis of the origin of each currently known Minoan mitochondrial and y-DNA haplotypes. The uniform result of these analyses is that the Minoans and the Uralic peoples had a common homeland in the lower and middle Danube Basin, as well as the Black Sea coastal regions. This new result helps to reconcile archaeogenetics with linguistics, which have shown that the Minoan language belongs to the Uralic language family. Full article

The development of complete mitochondrial genome (mitogenome) reference data for inclusion in publicly available population databases is currently underway, and the generation of more high-quality mitogenomes will only enhance the statistical power of this forensically useful locus. To characterize mitogenome variation in Sweden, the mitochondrial DNA (mtDNA) reads from the SweGen whole genome sequencing (WGS) dataset were analyzed. To overcome the interference from low-frequency nuclear mtDNA segments (NUMTs), a 10% variant frequency threshold was applied for the analysis. In total, 934 forensic-quality mitogenome haplotypes were characterized. Almost 45% of the SweGen haplotypes belonged to haplogroup H. Nearly all mitogenome haplotypes (99.1%) were assigned to European haplogroups, which was expected based on previous mtDNA studies of the Swedish population. There were signature northern Swedish and Finnish haplogroups observed in the dataset (e.g., U5b1, W1a), consistent with the nuclear DNA analyses of the SweGen data. The complete mitogenome analysis resulted in high haplotype diversity (0.9996) with a random match probability of 0.15%. Overall, the SweGen mitogenomes provide a large mtDNA reference dataset for the Swedish population and also contribute to the effort to estimate global mitogenome haplotype frequencies. Full article

We assessed the potential negative effects of bacteriostatic and bactericidal antibiotics on the AMD cybrid cell lines (K, U and J haplogroups). AMD cybrid cells were created and cultured in 96-well plates and treated with tetracycline (TETRA) and ciprofloxacin (CPFX) for 24 h. Reactive oxygen species (ROS) levels, mitochondrial membrane potential (ΔψM), cellular metabolism and ratio of apoptotic cells were measured using H2DCFDA, JC1, MTT and flow cytometry assays, respectively. Expression of genes of antioxidant enzymes, and pro-inflammatory and pro-apoptotic pathways were evaluated by quantitative real-time PCR (qRT-PCR). Higher ROS levels were found in U haplogroup cybrids when treated with CPFX 60 µg/mL concentrations, lower ΔψM of all haplogroups by CPFX 120 µg/mL, diminished cellular metabolism in all cybrids with CPFX 120 µg/mL, and higher ratio of dead cells in K and J cybrids. CPFX 120 µg/mL induced overexpression of IL-33, CASP-3 and CASP-9 in all cybrids, upregulation of TGF-β1 and SOD2 in U and J cybrids, respectively, along with decreased expression of IL-6 in J cybrids. TETRA 120 µg/mL induced decreased ROS levels in U and J cybrids, increased cellular metabolism of treated U cybrids, higher ratio of dead cells in K and J cybrids and declined ΔψM via all TETRA concentrations in all haplogroups. TETRA 120 µg/mL caused upregulation of IL-6 and CASP-3 genes in all cybrids, higher CASP-7 gene expression in K and U cybrids and downregulation of the SOD3 gene in K and U cybrids. Clinically relevant dosages of ciprofloxacin and tetracycline have potential adverse impacts on AMD cybrids possessing K, J and U mtDNA haplogroups in vitro. Full article

Retrieving high-quality endogenous ancient DNA (aDNA) poses several challenges, including low molecular copy number, high rates of fragmentation, damage at read termini, and potential presence of exogenous contaminant DNA. All these factors complicate a reliable reconstruction of consensus aDNA sequences in reads from high-throughput sequencing platforms. Here, we report findings from a thorough evaluation of two alternative tools (ANGSD and schmutzi) aimed at overcoming these issues and constructing high-quality ancient mitogenomes. Raw genomic data (BAM/FASTQ) from a total of 17 previously published whole ancient human genomes ranging from the 14th to the 7th millennium BCE were retrieved and mitochondrial consensus sequences were reconstructed using different quality filters, with their accuracy measured and compared. Moreover, the influence of different sequence parameters (number of reads, sequenced bases, mean coverage, and rate of deamination and contamination) as predictors of derived sequence quality was evaluated. Complete mitogenomes were successfully reconstructed for all ancient samples, and for the majority of them, filtering substantially improved mtDNA consensus calling and haplogroup prediction. Overall, the schmutzi pipeline, which estimates and takes into consideration exogenous contamination, appeared to have the edge over the much faster and user-friendly alternative method (ANGSD) in moderate to high coverage samples (>1,000,000 reads). ANGSD, however, through its read termini trimming filter, showed better capabilities in calling the consensus sequence from low-quality samples. Among all the predictors of overall sample quality examined, the strongest correlation was found for the available number of sequence reads and bases. In the process, we report a previously unassigned haplogroup (U3b) for an Early Chalcolithic individual from Southern Anatolia/Northern Levant. Full article

Mitochondrial DNA phylogenetic and phylogeographic studies have been very useful in reconstructing the history of modern humans. In addition, recent advances in ancient DNA techniques have enabled direct glimpses of the human past. Taking advantage of these possibilities, I carried out a spatiotemporal study of the rare and little-studied mtDNA haplogroup U8. Today, U8, represented by its main branches U8a and U8b, has a wide western Eurasian range but both with average frequencies below 1%. It is known that, in Paleolithic times, U8 reached high frequencies in European hunter-gatherers. However, it is pertinent to precise that only lineages belonging to U8a and U8c, a sister branch of U8b, were detected at that time. In spite of its wide geographic implantation, U8c was extinct after the Last Glacial Maximum, but U8a subsisted until the present day, although it never reached its high Paleolithic frequencies. U8a is detected mainly in northern and western Europe including the Basques, testifying to a minor maternal Paleolithic continuity. In this respect, it is worth mentioning that Basques show more U8-based affinities with continental European than with Mediterranean populations. On the contrary, coalescent ages of the most ancient U8b clades point to a Paleolithic diversification in the Caucasus and the Middle Eastern areas. U8b-derived branches reached eastern Europe since the Mesolithic. Subsequent Neolithic and post-Neolithic expansions widen its ranges in continental Europe and the Mediterranean basin, including northern Africa, albeit always as a minor clade that accompanied other, more representative, mitochondrial lineages. Full article

Mitochondrial encephalomyopathies (MEMP) are heterogeneous multisystem disorders frequently associated with mitochondrial DNA (mtDNA) mutations. Clinical presentation varies considerably in age of onset, course, and severity up to death in early childhood. In this study, we performed molecular genetic analysis for mtDNA pathogenic mutation detection in Serbian children, preliminary diagnosed clinically, biochemically and by brain imaging for mitochondrial encephalomyopathies disorders. Sanger sequencing analysis in three Serbian probands revealed two known pathogenic mutations. Two probands had a heteroplasmic point mutation m.3243A>G in the MT-TL1 gene, which confirmed mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episode syndrome (MELAS), while a single case clinically manifested for Leigh syndrome had an almost homoplasmic (close to 100%) m.8993T>G mutation in the MT-ATP6 gene. After full mtDNA MITOMASTER analysis and PhyloTree build 17, we report MELAS’ association with haplogroups U and H (U2e and H15 subclades); likewise, the mtDNA-associated Leigh syndrome proband shows a preference for haplogroup H (H34 subclade). Based on clinical–genetic correlation, we suggest that haplogroup H may contribute to the mitochondrial encephalomyopathies’ phenotypic variability of the patients in our study. We conclude that genetic studies for the distinctive mitochondrial encephalomyopathies should be well-considered for realizing clinical severity and possible outcomes. Full article

Genetic studies of population isolates have great potential to provide a unique insight into genetic differentiation and phenotypic expressions. Galičnik village is a population isolate located in the northwest region of the Republic of North Macedonia, established around the 10th century. Alport syndrome-linked nephropathy with a complex inheritance pattern has been described historically among individuals in the village. In order to determine the genetic basis of the nephropathies and to characterize the genetic structure of the population, 23 samples were genotyped using a custom-made next generation sequencing panel and 111 samples using population genetic markers. We compared the newly obtained population data with fifteen European population data sets. NGS analysis revealed four different mutations in three different collagen genes in twelve individuals within the Galičnik population. The genetic isolation and small effective population size of Galičnik village have resulted in a high level of genomic homogeneity, with domination of R1a-M458 and R1b-U106* haplogroups. The study explains complex autosomal in cis digenic and X-linked inheritance patterns of nephropathy in the isolated population of Galičnik and describes the first case of Alport syndrome family with three different collagen gene mutations. Full article

In order to assess the genomic landscape of the United Arab Emirates (UAE) mitogenome, we sequenced and analyzed the complete genomes of 232 Emirate females mitochondrial DNA (mtDNA) within and compared those to Africa. We investigated the prevalence of haplogroups, genetic variation, heteroplasmy, and demography among the UAE native population with diverse ethnicity and relatively high degree of consanguinity. We identified 968 mtDNA variants and high-resolution 15 haplogroups. Our results show that the UAE population received enough gene flow from Africa represented by the haplogroups L, U6, and M1, and that 16.8% of the population has an eastern provenance, depicted by the U haplogroup and the M Indian haplogroup (12%), whereas western Eurasian and Asian haplogroups (R, J, and K) represent 11 to 15%. Interestingly, we found an ancient migration present through the descendant of L (N1 and X) and other sub-haplogroups (L2a1d and L4) and (L3x1b), which is one of the oldest evolutionary histories outside of Africa. Our demographic analysis shows no population structure among populations, with low diversity and no population differentiation. In addition, we show that the transmission of mtDNA in the UAE population is under purifying selection with hints of diversifying selection on ATP8 gene. Last, our results show a population bottleneck, which coincides with the Western European contact (1400 ybp). Our study of the UAE mitogenomes suggest that several maternal lineage migratory episodes liking African–Asian corridors occurred since the first modern human emerges out of Africa. Full article

Distinguishing between maternal relatives through mitochondrial (mt) DNA sequence analysis has been a longstanding desire of the forensic community. Using a deep-coverage, massively parallel sequencing (DCMPS) approach, we studied the pattern of mtDNA heteroplasmy across the mtgenomes of 39 mother-child pairs of European decent; haplogroups H, J, K, R, T, U, and X. Both shared and differentiating heteroplasmy were observed on a frequent basis in these closely related maternal relatives, with the minor variant often presented as 2–10% of the sequencing reads. A total of 17 pairs exhibited differentiating heteroplasmy (44%), with the majority of sites (76%, 16 of 21) occurring in the coding region, further illustrating the value of conducting sequence analysis on the entire mtgenome. A number of the sites of differentiating heteroplasmy resulted in non-synonymous changes in protein sequence (5 of 21), and to changes in transfer or ribosomal RNA sequences (5 of 21), highlighting the potentially deleterious nature of these heteroplasmic states. Shared heteroplasmy was observed in 12 of the 39 mother-child pairs (31%), with no duplicate sites of either differentiating or shared heteroplasmy observed; a single nucleotide position (16093) was duplicated between the data sets. Finally, rates of heteroplasmy in blood and buccal cells were compared, as it is known that rates can vary across tissue types, with similar observations in the current study. Our data support the view that differentiating heteroplasmy across the mtgenome can be used to frequently distinguish maternal relatives, and could be of interest to both the medical genetics and forensic communities. Full article

The curse of ancient Egyptian DNA was lifted by a recent study which sequenced the mitochondrial genomes (mtGenome) of 90 ancient Egyptians from the archaeological site of Abusir el-Meleq. Surprisingly, these ancient inhabitants were more closely related to those from the Near East than to contemporary Egyptians. It has been accepted that the timeless highway of the Nile River seeded Egypt with African genetic influence, well before pre-Dynastic times. Here we report on the successful recovery and analysis of the complete mtGenome from a burial recovered from a remote Romano–Christian cemetery, Kellis 2 (K2). K2 serviced the ancient municipality of Kellis, a village located in the Dakhleh Oasis in the southwest desert in Egypt. The data were obtained by high throughput sequencing (HTS) performed independently at two ancient DNA facilities (Armed Forces DNA Identification Laboratory, Dover, DE, USA and Carl R. Woese Institute for Genomic Biology, University of Illinois Urbana-Champaign, Urbana, IL, USA). These efforts produced concordant haplotypes representing a U1a1a haplogroup lineage. This result indicates that Near Eastern maternal influence previously identified at Abusir el-Meleq was also present further south, in ancient Kellis during the Romano–Christian period. Full article