'Infertile' studies on mitochondrial DNA variation in asthenozoospermic Tunisian men

We reviewed five studies undertaken by the same research group on the possible links between mitochondrial DNA (mtDNA) variation and asthenozoospermia, all carried out on Tunisian men. A thorough assessment of these articles reveals that all five studies were carried out on virtually the same cohort of patients, although this information was concealed by the authors. Thus, the results were 'sliced' in order to unjustifiably maximize the number of publications. In addition, a phylogenetic analysis of their data indicates that the reported results are notably incomplete and deficient. Overall, contrary to the original claims, the association of mtDNA variants with asthenozoospermia finds no support on this saga on Tunisian infertile men.Instituto de Salud Carlos IIIF.M-T received funding fromthe GrantISCIII/INT14/00245 (Cofinanciado FEDER

A Genome-Wide Study of Modern-Day Tuscans: Revisiting Herodotus's Theory on the Origin of the Etruscans

Background: The origin of the Etruscan civilization (Etruria, Central Italy) is a long-standing subject of debate among scholars from different disciplines. The bulk of the information has been reconstructed from ancient texts and archaeological findings and, in the last few years, through the analysis of uniparental genetic markers. Methods: By meta-analyzing genome-wide data from The 1000 Genomes Project and the literature, we were able to compare the genomic patterns (.540,000 SNPs) of present day Tuscans (N = 98) with other population groups from the main hypothetical source populations, namely, Europe and the Middle East. Results: Admixture analysis indicates the presence of 25–34% of Middle Eastern component in modern Tuscans. Different analyses have been carried out using identity-by-state (IBS) values and genetic distances point to Eastern Anatolia/Southern Caucasus as the most likely geographic origin of the main Middle Eastern genetic component observed in the genome of modern Tuscans. Conclusions: The data indicate that the admixture event between local Tuscans and Middle Easterners could have occurred in Central Italy about 2,600–3,100 years ago (y.a.). On the whole, the results validate the theory of the ancient historian Herodotus on the origin of Etruscans.The research leading to these results has received funding from the ‘‘Ministerio de Ciencia e Innovacio´n’’ (SAF2011-26983) and from the Plan Galego IDT, Xunta de Galicia (EM 2012/045) (A.S.) and Consellerı´a de Sanidade/Xunta de Galicia (RHI07/2-intensificacio´n de la actividad investigadora and 10PXIB918184PR), Instituto Carlos III (Intensificacio´n de la actividad investigadora) and Fondo de Investigacio´n Sanitaria (FIS; PI07/0069, PI10/00540 and PI13/ 02382) of the Plan Nacional de I+D+I and ‘fondos FEDER’ (F.M.T.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.S

Mapping genome variation of SARS-CoV-2 worldwide highlights the impact of COVID-19 super-spreaders

The human pathogen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the major pandemic of the twenty-first century. We analyzed more than 4700 SARS-CoV-2 genomes and associated metadata retrieved from public repositories. SARS-CoV-2 sequences have a high sequence identity (>99.9%), which drops to >96% when compared to bat coronavirus genome. We built a mutation-annotated reference SARS-CoV-2 phylogeny with two main macro-haplogroups, A and B, both of Asian origin, and more than 160 sub-branches representing virus strains of variable geographical origins worldwide, revealing a rather uniform mutation occurrence along branches that could have implications for diagnostics and the design of future vaccines. Identification of the root of SARS-CoV-2 genomes is not without problems, owing to conflicting interpretations derived from either using the bat coronavirus genomes as an outgroup or relying on the sampling chronology of the SARS-CoV-2 genomes and TMRCA estimates; however, the overall scenario favors haplogroup A as the ancestral node. Phylogenetic analysis indicates a TMRCA for SARS-CoV-2 genomes dating to November 12, 2019, thus matching epidemiological records. Sub-haplogroup A2 most likely originated in Europe from an Asian ancestor and gave rise to subclade A2a, which represents the major non-Asian outbreak, especially in Africa and Europe. Multiple founder effect episodes, most likely associated with super-spreader hosts, might explain COVID-19 pandemic to a large extentThis study received support from the Instituto de Salud Carlos III: project GePEM (Instituto de Salud Carlos III(ISCIII)/PI16/01478/ Cofinanciado FEDER), DIAVIR (Instituto de Salud Carlos III(ISCIII)/DTS19/00049/Cofinanciado FEDER; Proyecto de Desarrollo Tecnológico en Salud) and Resvi-Omics (Instituto de Salud Carlos III(ISCIII)/PI19/01039/Cofinanciado FEDER) and project BI-BACVIR (PRIS-3; Agencia de Conocimiento en Salud (ACIS)—Servicio Gallego de Salud (SERGAS)—Xunta de Galicia; Spain) given to A.S.; and projects ReSVinext (Instituto de Salud Carlos III(ISCIII)/PI16/01569/Cofinanciado FEDER), and Enterogen (Instituto de Salud Carlos III(ISCIII)/ PI19/01090/ Cofinanciado FEDER) given to F.M.-TS

Genomic insights on the ethno-history of the Maya and the ‘Ladinos’ from Guatemala

Background Guatemala is a multiethnic and multilingual country located in Central America. The main population groups separate ‘Ladinos’ (mixed Native American-African-Spanish), and Native indigenous people of Maya descent. Among the present-day Guatemalan Maya, there are more than 20 different ethnic groups separated by different languages and cultures. Genetic variation of these communities still remains largely unexplored. The principal aim of this study is to explore the genetic variability of the Maya and ‘Ladinos’ from Guatemala by means of uniparental and ancestry informative markers (AIMs). Results Analyses of uniparental genetic markers indicate that Maya have a dominant Native American ancestry (mitochondrial DNA [mtDNA]: 100%; Y-chromosome: 94%). ‘Ladino’, however, show a clear gender-bias as indicated by the large European ancestry observed in the Y-chromosome (75%) compared to the mtDNA (0%). Autosomal polymorphisms (AIMs) also mirror this marked gender-bias: (i) Native American ancestry: 92% for the Maya vs. 55% for the ‘Ladino’, and (ii) European ancestry: 8% for the Maya vs. 41% for the ‘Ladino’. In addition, the impact of the Trans-Atlantic slave trade on the present-day Guatemalan population is very low (and only occurs in the ‘Ladino’; mtDNA: 9%; AIMs: 4%), in part mirroring the fact that Guatemala has a predominant orientation to the Pacific Ocean instead of a Caribbean one. Sequencing of entire Guatemalan mitogenomes has led to improved Native American phylogeny via the addition of new haplogroups that are mainly observed in Mesoamerica and/or the North of South America. Conclusions The data reveal the existence of a fluid gene flow in the Mesoamerican area and a predominant unidirectional flow towards South America, most likely occurring during the Pre-Classic (1800 BC-200 AD) and the Classic (200–1000 AD) Eras of the Mesoamerican chronology, coinciding with development of the most distinctive and advanced Mesoamerican civilization, the Maya. Phylogenetic features of mtDNA data also suggest a demographic scenario that is compatible with moderate local endogamy and isolation in the Maya combined with episodes of gene exchange between ethnic groups, suggesting an ethno-genesis in the Guatemalan Maya that is recent and supported on a cultural rather than a biological basis.We greatly thank all the sample contributors in Guatemala. JS was supported by research grants from the German FAZIT-STIFTUNG and the German Academic Exchange Service (DAAD). VAI was supported by funding from the EUROFORGEN project and the Xunta de Galicia (EM 2012/045). The research leading to these results has received funding from the People Program (Marie Curie Actions) of the European Union’s Seventh Framework Program FP7/2007-2013/ under REA grant agreement n° 290344, and the grants from the “Ministerio de Ciencia e Innovación” (SAF2008-02971) from the Plan Galego IDT, Xunta de Galicia (EM 2012/045) given to ASS

A Meta-Analysis of Multiple Whole Blood Gene Expression Data Unveils a Diagnostic Host-Response Transcript Signature for Respiratory Syncytial Virus

Respiratory syncytial virus (RSV) is one of the major causes of acute lower respiratory tract infection worldwide. The absence of a commercial vaccine and the limited success of current therapeutic strategies against RSV make further research necessary. We used a multi-cohort analysis approach to investigate host transcriptomic biomarkers and shed further light on the molecular mechanism underlying RSV-host interactions. We meta-analyzed seven transcriptome microarray studies from the public Gene Expression Omnibus (GEO) repository containing a total of 922 samples, including RSV, healthy controls, coronaviruses, enteroviruses, influenzas, rhinoviruses, and coinfections, from both adult and pediatric patients. We identified > 1500 genes differentially expressed when comparing the transcriptomes of RSV-infected patients against healthy controls. Functional enrichment analysis showed several pathways significantly altered, including immunologic response mediated by RSV infection, pattern recognition receptors, cell cycle, and olfactory signaling. In addition, we identified a minimal 17-transcript host signature specific for RSV infection by comparing transcriptomic profiles against other respiratory viruses. These multi-genic signatures might help to investigate future drug targets against RSV infectionThis study received support from the Instituto de Salud Carlos III: project GePEM (Instituto de Salud Carlos III(ISCIII)/PI16/01478/Cofinanciado FEDER), DIAVIR (Instituto de Salud Carlos III(ISCIII)/DTS19/00049/Cofinanciado FEDER; Proyecto de Desarrollo Tecnológico en Salud) and Resvi-Omics (Instituto de Salud Carlos III(ISCIII)/PI19/0103; 9/Cofinanciado FEDER) given to A.S.; and project ReSVinext (Instituto de Salud Carlos III(ISCIII)/PI16/01569/Cofinanciado FEDER), and Enterogen (Instituto de Salud Carlos III(ISCIII)/ PI19/01090/Cofinanciado FEDER) given to F.M.-T.S

The complete mitogenome of a 500-year-old Inca child mummy

In 1985, a frozen mummy was found in Cerro Aconcagua (Argentina). Archaeological studies identified the mummy as a seven-year-old Inca sacrifice victim who lived >500 years ago, at the time of the expansion of the Inca Empire towards the southern cone. The sequence of its entire mitogenome was obtained. After querying a large worldwide database of mitogenomes (>28,000) we found that the Inca haplotype belonged to a branch of haplogroup C1b (C1bi) that has not yet been identified in modern Native Americans. The expansion of C1b into the Americas, as estimated using 203 C1b mitogenomes, dates to the initial Paleoindian settlements (~18.3 thousand years ago [kya]); however, its internal variation differs between Mesoamerica and South America. By querying large databases of control region haplotypes (>150,000), we found only a few C1bi members in Peru and Bolivia (e.g. Aymaras), including one haplotype retrieved from ancient DNA of an individual belonging to the Wari Empire (Peruvian Andes). Overall, the results suggest that the profile of the mummy represents a very rare sub-clade that arose 14.3 (5–23.6) kya and could have been more frequent in the past. A Peruvian Inca origin for present-day C1bi haplotypes would satisfy both the genetic and paleo-anthropological findings.The research leading to these results has received funding from the “Ministerio de Ciencia e Innovación” (SAF2011–26983), the Plan Galego IDT (EM 2012/045) and a grant from the Sistema Universitario Gallego- Modalidad REDES (2012-PG226) from the Xunta de Galicia (A.S.); Instituto Carlos III (Intensificación de la actividad investigadora) and Fondo de Investigación Sanitaria (FIS; PI10/00540 and PI13/02382) of the Plan Nacional de I+ D+ I and Fondos FEDER (F.M.T)S

Arrival of Paleo-Indians to the Southern Cone of South America: New Clues from Mitogenomes

With analyses of entire mitogenomes, studies of Native American mitochondrial DNA (mtDNA) variation have entered the final phase of phylogenetic refinement: the dissection of the founding haplogroups into clades that arose in America during and after human arrival and spread. Ages and geographic distributions of these clades could provide novel clues on the colonization processes of the different regions of the double continent. As for the Southern Cone of South America, this approach has recently allowed the identification of two local clades (D1g and D1j) whose age estimates agree with the dating of the earliest archaeological sites in South America, indicating that Paleo-Indians might have reached that region from Beringia in less than 2000 years. In this study, we sequenced 46 mitogenomes belonging to two additional clades, termed B2i2 (former B2l) and C1b13, which were recently identified on the basis of mtDNA control-region data and whose geographical distributions appear to be restricted to Chile and Argentina. We confirm that their mutational motifs most likely arose in the Southern Cone region. However, the age estimate for B2i2 and C1b13 (11–13,000 years) appears to be younger than those of other local clades. The difference could reflect the different evolutionary origins of the distinct South American-specific sub-haplogroups, with some being already present, at different times and locations, at the very front of the expansion wave in South America, and others originating later in situ, when the tribalization process had already begun. A delayed origin of a few thousand years in one of the locally derived populations, possibly in the central part of Chile, would have limited the geographical and ethnic diffusion of B2i2 and explain the present-day occurrence that appears to be mainly confined to the Tehuelche and Araucanian-speaking grou

Whole mitochondrial DNA sequencing in Alpine populations and the genetic history of the Neolithic Tyrolean Iceman

The Tyrolean Iceman is an extraordinarily well-preserved natural mummy that lived south of the Alpine ridge ~5,200 years before present (ybp), during the Copper Age. Despite studies that have investigated his genetic profile, the relation of the Iceman´s maternal lineage with present-day mitochondrial variation remains elusive. Studies of the Iceman have shown that his mitochondrial DNA (mtDNA) belongs to a novel lineage of haplogroup K1 (K1f) not found in extant populations. We analyzed the complete mtDNA sequences of 42 haplogroup K bearing individuals from populations of the Eastern Italian Alps – putatively in genetic continuity with the Tyrolean Iceman—and compared his mitogenome with a large dataset of worldwide K1 sequences. Our results allow a re-definition of the K1 phylogeny and indicate that the K1f haplogroup is absent or rare in present-day populations. We suggest that mtDNA Iceman´s lineage could have disappeared during demographic events starting in Europe from ~5,000 ybp. Based on the comparison of our results with published data, we propose a scenario that could explain the apparent contrast between the phylogeographic features of maternal and paternal lineages of the Tyrolean Iceman within the context of the demographic dynamics happening in Europe from 8,000 ybp.This study was financed by the Provincia Autonoma di Bolzano – Alto Adige, Ripartizione Diritto allo studio, università e ricerca scientifica, funds to VCS

The impact of modern migrations on present-day multi-ethnic Argentina as recorded on the mitochondrial DNA genome

<p>Abstract</p> <p>Background</p> <p>The genetic background of Argentineans is a mosaic of different continental ancestries. From colonial to present times, the genetic contribution of Europeans and sub-Saharan Africans has superposed to or replaced the indigenous genetic 'stratum'. A sample of 384 individuals representing different Argentinean provinces was collected and genotyped for the first and the second mitochondrial DNA (mtDNA) hypervariable regions, and selectively genotyped for mtDNA SNPs. This data was analyzed together with additional 440 profiles from rural and urban populations plus 304 from Native American Argentineans, all available from the literature. A worldwide database was used for phylogeographic inferences, inter-population comparisons, and admixture analysis. Samples identified as belonging to hg (hg) H2a5 were sequenced for the entire mtDNA genome.</p> <p>Results</p> <p>Phylogenetic and admixture analyses indicate that only half of the Native American component in urban Argentineans might be attributed to the legacy of extinct ancestral Argentineans and that the Spanish genetic contribution is slightly higher than the Italian one. Entire H2a5 genomes linked these Argentinean mtDNAs to the Basque Country and improved the phylogeny of this Basque autochthonous clade. The fingerprint of African slaves in urban Argentinean mtDNAs was low and it can be phylogeographically attributed predominantly to western African. The European component is significantly more prevalent in the Buenos Aires province, the main gate of entrance for Atlantic immigration to Argentina, while the Native American component is larger in North and South Argentina. AMOVA, Principal Component Analysis and hgs/haplotype patterns in Argentina revealed an important level of genetic sub-structure in the country.</p> <p>Conclusions</p> <p>Studies aimed to compare mtDNA frequency profiles from different Argentinean geographical regions (e.g., forensic and case-control studies) should take into account the important genetic heterogeneity of the country in order to prevent false positive claims of association in disease studies or inadequate evaluation of forensic evidence.</p

GUANIN: an all-in-one GUi-driven analyzer for NanoString interactive normalization

GUANIN can be installed with pip install GUANIN and it is available at https://pypi.org/project/guanin/. Source code, documentation, and case studies are available at https://github.com/julimontoto/guanin under the GPLv3 license.[Abstract]: Most tools for normalizing NanoString gene expression data, apart from the default NanoString nCounter software, are R packages that focus on technical normalization and lack configurable parameters. However, content normalization is the most sensitive, experiment-specific, and relevant step to preprocess NanoString data. Currently this step requires the use of multiple tools and a deep understanding of data management by the researcher. We present GUANIN, a comprehensive normalization tool that integrates both new and well-established methods, offering a wide variety of options to introduce, filter, choose, and evaluate reference genes for content normalization. GUANIN allows the introduction of genes from an endogenous subset as reference genes, addressing housekeeping-related selection problems. It performs a specific and straightforward normalization approach for each experiment, using a wide variety of parameters with suggested default values. GUANIN provides a large number of informative output files that enable the iterative refinement of the normalization process. In terms of normalization, GUANIN matches or outperforms other available methods. Importantly, it allows researchers to interact comprehensively with the data preprocessing step without programming knowledge, thanks to its easy-to-use Graphical User Interface (GUI).The supercomputer FinisTerrae III and its permanent data storage system have been funded by the Spanish Ministry of Science and Innovation, the Galician Government, and the European Regional Development Fund (ERDF). This study also received support by (i) ISCIII: TRINEO: PI22/00162; DIAVIR: DTS19/00049; Resvi-Omics: PI19/01039 (A.S.), ReSVinext: PI16/01569, Enterogen: PI19/01090 (F.M.-T.), cofinanciados FEDER, (ii) GAIN: IN607B 2020/08 and IN607A 2023/02 (A.S.), GEN-COVID: IN845D 2020/23 (F.M.-T.), IIN607A2021/05 (F.M.-T.); (iii) ACIS: BI-BACVIR (PRIS-3, to A.S.), CovidPhy (SA 304 C, to A.S.); and (iv) consorcio Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CB21/06/00103; to A.S. and F.M.-T.). In addition, this study has been funded by ISCIII through the project “CP23/00080” and co-funded by the European Union. The funders were not involved in the study design, collection, analysis, interpretation of data, the writing of this article, or the decision to submit it for publication.Xunta de Galicia; IN607B 2020/08Xunta de Galicia; IN607A 2023/02Xunta de Galicia; IN845D 2020/23Xunta de Galicia; IIN607A2021/05Centro de Investigación Biomédica en Red de Enfermedades Respiratorias; CB21/06/0010