Search Results (218)

Background/Objectives: Mitochondrial DNA (mtDNA) is an important resource for understanding human ancestry, population diversity, and the molecular mechanisms of mitochondrial diseases. However, analyzing mtDNA thoroughly often requires advanced bioinformatics skills and command-line knowledge. To address this challenge, we created Mitochondrial Genome Explorer (MitoGEx), a user-friendly computational pipeline optimized for human mtDNA analysis that combines multiple mtDNA analysis modules within a single graphical user interface. Methods: The platform simplifies key analytical steps, such as quality control, sequence alignment, alignment quality assessment, variant detection, haplogroup classification, and phylogenetic reconstruction. Users can choose between Quick and Advanced modes, which offer default settings or customizable options based on their analysis needs. To demonstrate its effectiveness, we analyzed 15 whole-exome sequencing (WES) samples from Songklanagarind Hospital using MitoGEx. Results: The sequencing data were of high quality, with over 92 percent of bases scoring above a Phred score and consistent GC content across all samples. Variant detection using the GATK mitochondrial pipeline and annotation with ANNOVAR and the MitImpact database revealed multiple high-confidence variants. Haplogroup classification with Haplogrep 3 and phylogenetic analysis with IQ-TREE 2 confirmed diverse maternal lineages within the cohort. Conclusions: Taken together, MitoGEx facilitates mitochondrial genome analysis in a reproducible and accessible manner for both research and clinical bioinformatics applications. The analytical results produced by MitoGEx are concordant with those obtained using standalone bioinformatic tools, demonstrating analytical correctness. By integrating all analysis steps into a single automated workflow, MitoGEx reduces execution time and limits human error inherent to manual, multi-step pipelines. Full article

Mitochondria are crucial carriers of maternal effects, and their function is closely related to energy metabolism and disease occurrence. Previous studies have shown that chickens with different mitochondrial haplogroups exhibit differences in production performance, but the underlying mechanism remains unclear. This study investigates the differences in mitochondrial structure and function-related indices between the A and E mitochondrial haplogroups (referred to as A-group and E-group) in recessive white-feathered chickens. It was achieved using in vivo fasting/refeeding models and an in vitro model of treating hepatocytes with nutritional factors (glucose and fatty acids). In vivo study indicated that compared to A-group chicken hepatocytes, E-group hepatocytes had shorter perimeters of mitochondria and shorter lengths of mitochondria associated with the endoplasmic reticulum membrane during refeeding (p < 0.05); mitochondria were more abundant (p = 0.05) but displayed compromised structural integrity during fasting; mitochondrial swelling was more severe during both refeeding and fasting (p < 0.01, p < 0.05); the protein level of mitofusin 2 (MFN2) was lower during fasting (p < 0.05); and there were more vacuoles and lipid accumulation in liver sections during refeeding (p < 0.05). In cultured hepatocytes, compared to A-group cells, E-group cells had higher reactive oxygen species (ROS) level after oleic acid treatments (p < 0.001); the protein level of microtubule-associated protein 1A/1B-light chain 3 beta (LC3) was lower after glucose treatment (p < 0.01), and the protein levels of MFN2 and LC3 were lower after oleic acid treatment (p < 0.01, p < 0.05). These findings suggest that mitochondrial haplogroups are associated with mitochondrial structure and function, oxidative stress, autophagy, and lipid metabolism of chicken hepatocytes in response to energy stimulation. The findings may explain how mitochondrial haplogroups affect chicken production performance. Full article

Background: Dendroctonus armandi, an oligophagous beetle primarily infesting Pinus armandii, is geographically restricted and persistent in central China, causing significant ecological and economic losses. However, the intrinsic factors driving its continuous occurrence remain unclear. We examined the genetic variation patterns across the species’ range to explore its phylogeographic structure. Methods: We analyzed mitochondrial DNA sequence (mtDNA) data to assess population genetic structure and estimate the divergence times of distinct lineages. Results: Phylogenetic analysis identified four haplogroups corresponding to the Minshan (MSM), Qinling (QLM), Micang (MCM), and Ta-pa (TPM) Mountains. Demographic analyses revealed that QLM and TPM haplogroups have undergone population expansion events. Divergence time estimates indicated four lineages diverged during the Late Pleistocene. Notably, D. armandi may have followed two horizontal and one vertical independent colonization routes. The first route extended from MSM into QLM and then spread eastward along the QLM; the second route progressed from MSM into MCM and continued eastward into TPM; and the third route migrated southward from QLM into TPM. Conclusions: Climate oscillations, geographical isolation, and the patchy distribution of host trees collectively shaped the phylogeographic patterns of D. armandi. These findings elucidate the evolution and adaptability of D. armandi in mountainous environments. Full article

Background: Microarray testing is commonly used as a screening method for phenotypic traits and common diseases and for genome-wide association studies (GWASs). Despite the known limitations, microarray services can potentially be used as a prescreening tool for chromosomal disorders, which affect approximately 0.4–0.6% of the world population, followed by further clinical diagnostic methods when appropriate. Case Presentation: Here we present a case study of a male subject in his 40s who underwent direct-to-consumer (DTC) genetic testing that utilized microarray, which revealed the absence of Y chromosome haplogroup data despite possessing a typical male phenotype. Subsequent medical consultation, whole-genome sequencing (WGS), and chromosomal analysis confirmed a diagnosis of 46,XX testicular differences of sex development (DSD, formerly XX male syndrome) characterized by the presence of Y chromosome-derived genomic material, including the SRY gene. An initial microarray test gave an indeterminate result for the Y chromosome call rate and an X chromosome heterozygosity result that aligned with the female average. These indeterminate results, coupled with the subject’s male phenotype, led to further testing—WGS, karyotyping, fluorescence in situ hybridization using an SRY Probe, and endocrine testing. From these results, the subject was diagnosed with 46,XX testicular DSD. Conclusions: To our knowledge, this represents the first reported case where 46,XX testicular DSD was diagnosed starting from a DTC test which led to medical consultation and comprehensive genomic and cytogenetic analysis. This case underscores the potential diagnostic value of consumer-initiated DTC microarray screening in the era of genomic medicine and for supporting social needs such as gender confirmation for sports. Full article

Rapid pain progression in knee osteoarthritis (OA) is heterogeneous and may reflect redox-related mechanisms. We performed an exploratory analysis in Osteoarthritis Initiative (OAI) participants, combining nuclear genome-wide association, mitochondrial DNA (mtDNA) haplogroups, and leukocyte telomere length. Rapid pain progression was defined using the rescaled Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) for pain (0–100) within 24-month windows. An additive genome-wide association study (GWAS) in 2946 participants tested 7,762,204 imputed variants, adjusting for age, sex, body mass index (BMI) and three principal components. Haplogroups were analysed in 3357 participants, and telomere length (telomere-to-single-copy gene, T/S, ratio) was analysed in 301 participants. No variant reached genome-wide significance (p < 5 × 10⁻⁸), but six loci were suggestive (p < 5 × 10⁻⁶), with minimal inflation (λ = 0.995). mtDNA haplogroup H was nominally associated with rapid pain progression (odds ratio, OR = 1.179, p = 0.023). Rapid pain progressors had shorter baseline telomeres (0.825 ± 0.268 vs. 0.985 ± 0.375; p < 0.001), and telomere length was inversely associated with progression (OR per 1-unit T/S = 0.260, p = 0.007). These preliminary, hypothesis-generating findings are compatible with a redox-related interpretation of rapid pain progression and require external validation in independent cohorts, while providing candidates for future mechanistic studies. Full article

Background/Objectives: Arctic foxes (Vulpes lagopus) exemplify the vulnerability of Arctic species to global warming and anthropogenic impacts, including habitat loss, interspecific competition with temperate species, pollution (chemical and biological), and declining prey abundance. Despite their ecological importance, the evolutionary and demographic history of the species is still incompletely understood, and the colonization history of isolated island populations, such as the one on Iceland, remains unresolved. Methods: We analyzed 80 mitochondrial genomes from across the Holarctic, including 22 Icelandic individuals. We combined phylogenetic reconstruction, coalescence-dating, haplotype network analysis, and diversity metrics to infer matrilineal relationships and colonization history. Results: Seven distinct haplogroups (Hg.1–Hg.7) were identified, which diverged ≥65 thousand years ago (kya). Two haplogroups were broadly distributed across Fennoscandia, Russia, Iceland, and Canada, while others were region-specific: two in eastern Russia (respectively diverging ~171 kya and ~89 kya), one in central Russia (~66 kya), and two in Iceland (~95 kya and ~66 kya). Three haplogroups were detected in Iceland, and at least four unrelated founding females are required to explain the current matrilineal diversity. One haplogroup contained sufficient representatives for molecular dating, yielding a minimum colonization age of ~5600 years, assuming in situ diversification. Observed matrilineal diversity in Iceland does not uniquely identify a single geographic source. Conclusions: Arctic foxes’ distribution and diversity reflect repeated cycles of isolation and expansion as circumpolar environments shifted. Broader sampling across the Nearctic is critical to clarify the timing, sources, and routes of Iceland’s colonization, as Nearctic sampling was limited to a single Canadian mitogenome. Full article

Background/Objectives: The Bedouins (nomads) and the Fellahin (farmers) of Jordan represent two distinct subpopulations, characterized by unique lifestyles, settlement patterns, and linguistic features. This study aims to estimate the frequency of 27 Y-STRs in these two Jordanian subpopulations, along with various forensic parameters and paternal lineage comparisons with neighboring populations. Methods: Twenty-seven Y-STRs were typed in two major Jordanian subpopulations: Bedouin nomads (n = 101) and Fellahin farmers (n = 98). The forensic and paternal genetic lineage parameters and Y-haplogroup predictions were estimated. In addition, we conducted multidimensional scaling (MDS) and centroid analyses based on the Fst distance matrix to compare the sampled communities with neighboring populations from the MENA region, East Africa, Southeast Europe, and South Asia. Results: The Y-haplogroup predictions revealed differences in the predicted lineage composition based on the Y-STR profiles. The predicted J1a2a1a2 haplogroup predominated among the Bedouins (74.3%), whereas the Fellahin displayed a more heterogeneous profile, with notable frequencies of J1 (40%) and J2 (17.3%). Furthermore, the Fellahin exhibited remarkable genetic diversity and significant gene flow, providing plausible evidence of kinship with neighboring Levantine and Arabian groups. In contrast, the Bedouins showed consistently lower diversity across multiple loci, indicating long-term tribal isolation and, therefore, the potential effects of genetic drift. The MDS and centroid analyses positioned the Fellahin among the genetically interconnected Middle Eastern populations, while the Bedouins were clustered with the Arabian Peninsula populations. Conclusions: Overall, the contrasting genetic signatures of the two Jordanian subpopulations reflect their settlement patterns and sociocultural practices. In addition, the Y-STR dataset generated in this study enhances the Jordanian forensic database and to extends our understanding of paternal lineage structures in the West Asian/Levantine region. Full article

Background: Short tandem repeats (STRs) are highly variable sequences present along the human genome, including the Y-chromosome. Y-STRs are exclusive to males, and the haplotypes they define are informative. Objectives: Twenty-six Y-STR loci were genotyped in 252 males from Northern Portugal to characterise Y-chromosome genetic variation using the Investigator Argus Y28 QS Kit. Methods: The kit mentioned was used to amplify male DNA samples, and capillary electrophoresis was used to analyze the fragments. Forensic parameters and haplotype diversity were computed, and samples’ haplogroups were predicted. A multidimensional scaling (MDS) plot was used to graphically represent the R_ST genetic distances, including reference populations. Results: A total of 250 different haplotypes were observed, including 248 unique ones, yielding a very high haplotype diversity (HD = 0.999) and discriminatory power (DP = 0.992). Haplogroup analysis indicated a predominance of R1b (58.7%), followed by E1b1b, I and J, pointing to a population history shaped by Mediterranean and North African gene flow. Comparative analysis between Portugal and 5 other populations showed greater genetic affinity with Spain and Italy, while revealing marked differentiation from Greece, Morocco, and former Portuguese colonies. Conclusions: The results confirm that the Northern Portuguese Population exhibits high Y-STR variability and robust forensic resolution. The dataset was submitted to the YHRD database, enhancing the representation of the Portuguese population and underscoring the value of the 26 locus panel for applications in forensic science, genealogy, and population genetics. Full article

Studying intraspecific differentiation in closely related species is essential to clarify the phylogenetic relationships and mechanisms of early stage speciation, particularly in evolutionarily young lineages affected by human-driven population declines. The endangered saker falcon (Falco cherrug), with its ambiguous phylogenetic links to the gyrfalcon (F. rusticolus), exemplifies this scenario. This study presents a comprehensive genetic analysis of F. cherrug and F. rusticolus using mtDNA markers and microsatellite loci, focusing on the diversity of southern Siberian saker falcon populations. The genotyping results for these populations were correlated with phenotypic data obtained from long-term monitoring (1999–2021). Our findings provide novel insights into the current subspecific differentiation and the remnants of a nascent subspecies structure that existed before the recent demographic collapse. Furthermore, our results support the hypothesis of the gyrfalcon’s origin as a descendant species of the Asian saker falcon, i.e., an evolutionarily young lineage undergoing divergence. Our data contribute to the understanding of the Hierofalco evolutionary history, particularly through the analysis of heterogeneous mutation rates among mitochondrial haplogroups. This study underscores the critical importance of conservation efforts for wild endangered populations through long-term monitoring integrated with combined genetic approaches. Full article

Background/Objectives: Southeastern Europe and Croatia have served as a genetic crossroads between the Near East and Europe since prehistoric times, shaped by numerous and repeated migrations. By integrating 19 newly generated ancient genomes with 285 previously published ancient genomes from Croatia, we investigated patterns of maternal and paternal landscapes from the Neolithic, Bronze, and Iron Ages through to the Antiquity and medieval periods, as well as the modern Croatian population. Methods: Ancient DNA extraction from human remains and library preparation were conducted in dedicated clean-room facilities, followed by high-throughput sequencing on the Illumina platform. Sequencing data were analyzed with established pipelines to determine mitochondrial and Y-chromosomal haplogroups and the genetic sex of individuals. Results: New ancient data reveal a predominantly European maternal profile, dominated by haplogroups H, U, and HV0, whereas Y-chromosomal lineages are characterized by J subclades and R1a, with limited representation of R1b and the absence of I2a. When combined with published ancient Croatian genomes, the results reveal similar haplogroup diversity and patterns, as well as the expansion of mtDNA haplogroup H over time and a substantial increase in Y-chromosome R1a and I2a haplogroup frequency from the prehistoric to the modern period. Conclusions: Although the analyzed samples are heterogeneous and originate from different historical periods, their genetic signatures conform to the broader patterns expected for the region. In a wider context, the ancient Croatian mitochondrial data reveal stronger genetic persistence from prehistory to modern times, unlike paternal lineages, which show significantly higher divergence. Full article

Mitochondria, which have critical roles in energy metabolism and oxidative regulation, also have a role in immune regulation including T cell activation, NET formation, inflammation, and apoptosis. More than 50% of those with systemic lupus erythematosus (SLE) have lupus nephritis due to kidney damage from immune complex deposition. Disease severity is reported to be greater in certain lineages. Mitochondrial DNA (mtDNA) haplogroups, which reflect maternal lineages, may modulate immune balance and disease outcomes in SLE. Methods: DNA was extracted from 25 consecutive, consenting pediatric patients that fulfilled the 1997 criteria for SLE and their maternal mitochondrial DNA (mtDNA) haplogroups were determined through next-generation sequencing (NGS). Results: This study evaluated the associations between mtDNA haplogroups, lupus nephritis, and organ damage in four mtDNA haplogroups: African (n = 5), Amerindian (n = 12), Asian (n = 4), and Caucasian (n = 4). Clinical data, SLE Disease Activity Index (SLEDAI-2K), SLICC Damage Index (SDI), and renal biopsy findings were analyzed. Median SLEDAI-2K scores were higher in Amerindian (10) and African (8) patients than in the Caucasian (5.5) and Asian (3) groups, with significant differences between Amerindian vs. Caucasian (p = 0.045) and Amerindian vs. Asian (p = 0.008). Irreversible organ damage (SDI > 1) was more frequent in Amerindian (54%) and African (40%) patients. Lupus nephritis occurred most often and most severely (Class III–IV, CKD) in the Amerindian (85%) and African (80%) groups, while Caucasian and Asian patients more often showed milder, membranous disease without CKD. Conclusion: Although limited by the small sample size, pediatric SLE severity and renal involvement were found to be greater in Amerindian and African mtDNA haplogroups, suggesting that mitochondrial lineage may contribute to ethnic disparities in SLE. Full article

Congenital toxoplasmosis presents with a wide clinical spectrum, ranging from asymptomatic infection to severe disease with multi-organ failure. We report a rare fatal case of disseminated congenital toxoplasmosis in a human neonate. The infant initially had thrombocytopenia and mild hepatitis, which rapidly progressed to fulminant liver failure. Despite initiation of standard therapy with pyrimethamine, sulfadiazine, and folinic acid on postnatal day 25, the infant died two days later. Autopsy revealed widespread involvement of the liver, spleen, brain, heart, lungs, urinary bladder, and skeletal muscle. To further characterize the infection, genomic sequencing of the isolate (TgHsUS2) was performed, which placed it within clade C (Haplogroup 9) and closely related to reference strains P89 and TgCatBr3. Variant analysis showed type III-like alleles in ROP18, ROP16, and GRA15. These alleles are known to modulate host immunity and may have influenced disease severity in this case. This report highlights the need for rapid recognition and targeted therapy as well as how strain genomics can inform disease mechanisms. Prevention through prenatal screening and maternal treatment during pregnancy may reduce infant mortality. Full article

Background/Objectives: In Brazil, quilombos—African-descendant resistance communities—emerged during slavery and persisted beyond its abolition. The state of Paraná, in Southern Brazil, is home to 86 quilombos, yet their genetic diversity remains entirely unexplored, and little is known about their subcontinental African origins. Methods: To explore the demographic history of these communities and the reach of the Transatlantic Slave Trade in Southern Brazil, we analyzed Y and mitochondrial DNA haplotypes in samples from two quilombo communities from Paraná, Feixo (n = 117) and Restinga (n = 47). Results: Our findings reveal a significant African maternal ancestry in both communities, with Feixo exhibiting 35% and Restinga showing a striking 78.72% of maternal haplogroups of African origin. Feixo’s mtDNA haplotypes display affinities with Bantu-speaking populations from Central-Western and Southeastern Africa (such as Angola, Congo, and Mozambique), whereas those found in Restinga are more closely aligned with lineages frequent in Western Africa. Y-chromosome data reveal 39.4% and 25% African paternal ancestry in Feixo and Restinga, respectively, with most African chromosomes assigned to haplogroup E1b1b1-M35, which has a broad frequency across eastern Africa. Conclusions: These results offer novel insights into the history of the African diaspora in a previously unstudied Brazilian region, suggesting African sources—including underdocumented Eastern/Southern lineages—and contributing useful new clues to their broader within-Africa affinities. Full article

Background: A comprehensive temporal analysis of mtDNA haplogroup variation across Lithuanian history remains limited. This study investigates the mtDNA variation landscape during the Iron Age by comparing newly reported Iron Age individual mtDNA data with the new data from present-day Lithuanians. Methods: Remains of individuals from the Iron Age Lithuania (n = 101) were processed using standard protocols for ancient DNA processing. For the present-day Lithuanians (n = 279), whole mitogenomes were sequenced. Thirty-six polymorphic sites within the Hypervariable Region I were used for haplogroup assignment, phylogenetic and population genetic analyses. Results: Fifteen distinct haplogroups in the Iron Age and the present-day Lithuanians were identified. Haplogroup R0/H remained the most frequent across time. Haplogroups U, T, and N were prominent in the Iron Age. Haplogroups M and D were introduced after the Iron Age. Phylogenetic and population genetic analyses revealed greater mtDNA diversity in the present-day Lithuanians. Significant difference in molecular variance was observed during the Iron Age. Barring the Viking period, the Iron Age mtDNA variation matched the present-day Lithuanian and European populations. Conclusions: Our study showed that mtDNA variation over time remained stable with some random fluctuations and gained more diversity in the present-day Lithuanians. Full article

The family name Hay (plus associated spelling variants) is a prominent Anglo-Norman-in-origin surname that has been well-documented as a Scottish noble lineage since the 12th century CE. Their historical significance, linked to the rise in the Anglo-Norman era (1093–1286 CE) in Scotland, and the historical complexities of surname adoption post-Norman conquest of England, justifies the need for a comprehensive understanding of the genetic history of the Hay noble lineage. This study focuses on examining the patterns of paternal inheritance in lineages with the Hay surname. We conducted a comprehensive analysis of Y-chromosome data that is publicly available on the Family Tree DNA (FTDNA) platform, and specific FTDNA surname projects, as well as looking in more detail at three well-documented male-line descendants of William II de la HAYA, 1st of Erroll (d. 1201) that have been verified to a high degree of confidence. Our results reveal that all descendants of William II de la HAYA, 1st of Erroll (d. 1201) derive from the multigenerational Y-SNPs R1a-YP6500 (plus equivalent SNPs BY33394/FT2017) and R1a-FTT161. Furthermore, subclades of R1a-FTT161 have been identified that confirm direct male-line descent from two of William II de la HAYA’s sons. Subclade R1a-BY199342 (plus equivalents) confirms direct male-line descent from David de la HAYA, 2nd of Erroll (d. 1241), and subclade R1a-FTA7312 confirms direct male-line descent from Robert de la HAYA of Erroll. The result also confirms that the Hay noble lineage shares the Y-SNP R1a-YP4138 (estimated to have occurred in 832 CE) with several non-Hay test takers that have surnames of Norman origin, therefore providing further evidence to support the Norman origin hypothesis for these surnames. In addition to the identification of multigenerational Y-SNPs associated with documented Hay noblemen, this study has observed significant Y-DNA haplogroup diversity among males with the surname Hay (plus associated spelling variants: Hays, Haye, Hayes, Hey and Haya). Our results show that only 22% of the men sampled (n = 109) with the surname Hay (plus associated spelling variation) are descended from the 12th-century progenitor of the noble Hay lineage of Scotland. Therefore, this confirms that a significant proportion of males with the surname Hay do not descend from the noble progenitor of the Scottish Hay lineage of Erroll. Full article