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Complex structural variations (cxSVs) are often overlooked in genome analyses due to detection challenges. We developed ARC-SV, a probabilistic and machine-learning-based method that enables accurate detection and reconstruction of cxSVs from standard datasets. By applying ARC-SV across 4,262 genomes representing all continental populations, we identified cxSVs as a significant source of natural human genetic variation. Rare cxSVs have a propensity to occur in neural genes and loci that underwent rapid human-specific evolution, including those regulating corticogenesis. By performing single-nucleus multiomics in postmortem brains, we discovered cxSVs associated with differential gene expression and chromatin accessibility across various brain regions and cell types. Additionally, cxSVs detected in brains of psychiatric cases are enriched for linkage with psychiatric GWAS risk alleles detected in the same brains. Furthermore, our analysis revealed significantly decreased brain-region- and cell-type-specific expression of cxSV genes, specifically for psychiatric cases, implicating cxSVs in the molecular etiology of major neuropsychiatric disorders. [Display omitted] • ARC-SV uses machine learning on pangenomes to detect cxSVs with high accuracy • Rare cxSVs in the human population are enriched in neural genes • Rare cxSVs are enriched in loci that underwent rapid human-specific evolution • cxSVs contribute to the genetic architecture of major psychiatric disorders ARC-SV enables highly accurate detection and characterization of localized complex rearrangements of multiple DNA segments. Applying ARC-SV across human populations and brain cohorts uncovers connections between complex structural variantion and human-specific evolution, neural genes, and major psychiatric disorders. [ABSTRACT FROM AUTHOR]

Ancient DNA provides a unique frame for directly studying human population genetics in time and space. Still, since most of the ancient genomic data is low coverage, analysis is confronted with a low number of SNPs, genotype uncertainties, and reference-bias. Here, we for the first time benchmark the two distinct versions of Glimpse tools on 120 ancient human genomes from Eurasia including those largely from previously under-evaluated regions and compare the performance of genotype imputation with de facto analysis approaches for low coverage genomic data analysis. We further investigate the impact of two distinct reference panels on imputation accuracy for low coverage genomic data. We compute accuracy statistics and perform PCA and f4-statistics to explore the behaviour of genotype imputation on low coverage data regarding (i)two versions of Glimpse, (ii)two reference panels, (iii)four post-imputation filters and coverages, as well as (iv)data type and geographical origin of the samples on the analyses. Our results reveal that even for 0.1X coverage ancient human genomes, genotype imputation using Glimpse-v2 is suitable. Additionally, using the 1000 Genomes merged with Human Genome Diversity Panel improves the accuracy of imputation for the rare variants with low MAF, which might be important not only for ancient genomics but also for modern human genomic studies based on low coverage data and for haplotype-based analysis. Most importantly, we reveal that genotype imputation of low coverage ancient human genomes reduces the genetic affinity of the samples towards human reference genome. Through solving one of the most challenging biases in data analysis, so-called reference bias, genotype imputation using Glimpse v2 is promising for low coverage ancient human genomic data analysis and for rare-variant-based and haplotype-based analysis. [ABSTRACT FROM AUTHOR]

Abstract Background North African human populations present a complex demographic scenario due to the presence of an autochthonous genetic component and population substructure, plus extensive gene flow from the Middle East, Europe, and sub-Saharan Africa. Results We conducted a comprehensive analysis of 364 genomes to construct detailed demographic models for the North African region, encompassing its two primary ethnic groups, the Arab and Amazigh populations. This was achieved through an Approximate Bayesian Computation with Deep Learning (ABC-DL) framework and a novel algorithm called Genetic Programming for Population Genetics (GP4PG). This innovative approach enabled us to effectively model intricate demographic scenarios, utilizing a subset of 16 whole genomes at > 30X coverage. The demographic model suggested by GP4PG exhibited a closer alignment with the observed data compared to the ABC-DL model. Both point to a back-to-Africa origin of North African individuals and a close relationship with Eurasian populations. Results support different origins for Amazigh and Arab populations, with Amazigh populations originating back in Epipaleolithic times, while GP4PG supports Arabization as the main source of Middle Eastern ancestry. The GP4PG model includes population substructure in surrounding populations (sub-Saharan Africa and Middle East) with continuous decaying gene flow after population split. Contrary to ABC-DL, the best GP4PG model does not require pulses of admixture from surrounding populations into North Africa pointing to soft splits as drivers of divergence in North Africa. Conclusions We have built a demographic model on North Africa that points to a back-to-Africa expansion and a differential origin between Arab and Amazigh populations.

Epidemiological studies frequently classify groups based on phenotypes like self-reported skin color/race, which inaccurately represent genetic ancestry and may lead to misclassification, particularly among individuals of multiracial backgrounds. This study aimed to characterize both global and local genome-wide genetic ancestries and to assess their relationship with self-reported skin color/race in an admixed population of Sao Paulo city. We analyzed 226,346 single-nucleotide polymorphisms from 841 individuals participating in the population-based ISA-Nutrition study. Our findings confirmed the admixed nature of the population, demonstrating substantial European, significant Sub-Saharan African, and minor Native American ancestries, irrespective of skin color. A correlation was observed between global genetic ancestry and self-reported color-race, which was more evident in the extreme proportions of African and European ancestries. Individuals with higher African ancestry tended to identify as Black, those with higher European ancestry tended to identify as White, and individuals with higher Native American ancestry were more likely to self-identify as Mixed, a group with diverse ancestral compositions. However, at the individual level, this correlation was notably weak, and no deviations were observed for specific regions throughout the individual's genome. Our findings emphasize the significance of accurately defining and thoroughly analyzing race and ancestry, especially within admixed populations. [ABSTRACT FROM AUTHOR]

Short tandem repeats (STRs) are the most common genetic markers in forensic and human population genetics due to their high polymorphism, rapid detection, and reliable genotyping. To adapt the rapid growth of forensic DNA database and solve problems in disputed cases, a panel of 23 autosomal STR loci with high discriminating ability was constructed recently. The Tai-Kadai-speaking Gelao is the most ancient indigenous minority in Guizhou province, however, the forensic efficiency and population genetic structure remain poorly explored. Here, 490 Guizhou Gelao individuals from Southwest China were genotyped with the panel of 23 STRs using the Huaxia Platinum Kit. A total of 265 alleles were screened. The combined discrimination power and the combined probability of paternity were 0.9999 and 0.9999, respectively. This indicated the 23 loci had higher discrimination power in Guizhou Gelao and could be applied to forensic practice. Comprehensive population structures with reference populations from China and abroad using the neighbour-joining phylogenetic tree (N-J tree), multidimensional scaling, principal component analysis and heatmap demonstrated that Guizhou Gelao was genetically closer to Guizhou Han than other populations. Moreover, our results showed that a complex phylogenetic model was influenced by ethnic, geographic, and linguistic factors. Key points The first batch of genetic data for 23 autosomal STRs in 490 Geolao individuals from Guizhou was provided. The 23 STR panel can afford high genetic polymorphisms and discrimination power and can be efficiently applied to forensic practice in Guizhou Gelao population. A complex phylogenetic model influenced by ethnic, geographic, and linguistic factors was uncovered. [ABSTRACT FROM AUTHOR]

X‐chromosome short tandem repeat (X‐STR) tools are crucial in forensic genetics and human population fields. This study presents the development and validation of a multiplex STR system consisting of thirteen X‐STR loci and amelogenin specific to the human X chromosome. The system was optimized and tested for species specificity, sensitivity, stability, and DNA mixture using 9947A female and 9948 male control genomic DNA. The amplified products of nine loci were sequenced to determine the correct amplicon length. Allele frequencies, forensic parameters, mean exclusion chance (MEC), linkage disequilibrium (LD), and allelic patterns were investigated using DNA samples from 225 (159 male, 66 female) unrelated Kurdish individuals who live in Sulaymaniyah province in the Kurdistan region of Iraq. The most informative locus in the Kurdish population was GATA172D05, while the least informative locus was DXS10164. The results demonstrated that the 13 X‐STR system is highly polymorphic and sensitive for forensic DNA identification. Genetic distance‐based clustering, metric multidimensional scaling (MDS), and correlation matrix were analyzed for 19 ethnic groups and populations. The phylogenetic tree showed that populations clustered according to their ethnogeographic relationships. The findings revealed genetic links between the Iraqi Kurds, Caucasians, Iraqi Arabs, United States (U.S.) ethnic groups, and Chinese populations. [ABSTRACT FROM AUTHOR]

The article focuses on the significance of studying human skeletons, dental plaque, and biomolecules to uncover hidden aspects of the past, particularly through paleogenomics. Topics include how molecular analyses reveal historical interactions between humans and their environment, the application of these findings to modern health issues and disease prevention, and the advancement of new therapeutic approaches through interdisciplinary research.

The ancestral recombination graph (ARG) is a structure that represents the history of coalescent and recombination events connecting a set of sequences (Hudson RR. In: Futuyma D, Antonovics J, editors. Gene genealogies and the coalescent process. In: Oxford Surveys in Evolutionary Biology; 1991. p. 1 to 44.). The full ARG can be represented as a set of genealogical trees at every locus in the genome, annotated with recombination events that change the topology of the trees between adjacent loci and the mutations that occurred along the branches of those trees (Griffiths RC, Marjoram P. An ancestral recombination graph. In: Donnelly P, Tavare S, editors. Progress in population genetics and human evolution. Springer; 1997. p. 257 to 270.). Valuable insights can be gained into past evolutionary processes, such as demographic events or the influence of natural selection, by studying the ARG. It is regarded as the "holy grail" of population genetics (Hubisz M, Siepel A. Inference of ancestral recombination graphs using ARGweaver. In: Dutheil JY, editors. Statistical population genomics. New York, NY: Springer US; 2020. p. 231–266.) since it encodes the processes that generate all patterns of allelic and haplotypic variation from which all commonly used summary statistics in population genetic research (e.g. heterozygosity and linkage disequilibrium) can be derived. Many previous evolutionary inferences relied on summary statistics extracted from the genotype matrix. Evolutionary inferences using the ARG represent a significant advancement as the ARG is a representation of the evolutionary history of a sample that shows the past history of recombination, coalescence, and mutation events across a particular sequence. This representation in theory contains as much information, if not more, than the combination of all independent summary statistics that could be derived from the genotype matrix. Consistent with this idea, some of the first ARG-based analyses have proven to be more powerful than summary statistic-based analyses (Speidel L, Forest M, Shi S, Myers SR. A method for genome-wide genealogy estimation for thousands of samples. Nat Genet. 2019:51(9):1321 to 1329.; Stern AJ, Wilton PR, Nielsen R. An approximate full-likelihood method for inferring selection and allele frequency trajectories from DNA sequence data. PLoS Genet. 2019:15(9):e1008384.; Hubisz MJ, Williams AL, Siepel A. Mapping gene flow between ancient hominins through demography-aware inference of the ancestral recombination graph. PLoS Genet. 2020:16(8):e1008895.; Fan C, Mancuso N, Chiang CWK. A genealogical estimate of genetic relationships. Am J Hum Genet. 2022:109(5):812–824.; Fan C, Cahoon JL, Dinh BL, Ortega-Del Vecchyo D, Huber C, Edge MD, Mancuso N, Chiang CWK. A likelihood-based framework for demographic inference from genealogical trees. bioRxiv. 2023.10.10.561787. 2023.; Hejase HA, Mo Z, Campagna L, Siepel A. A deep-learning approach for inference of selective sweeps from the ancestral recombination graph. Mol Biol Evol. 2022:39(1):msab332.; Link V, Schraiber JG, Fan C, Dinh B, Mancuso N, Chiang CWK, Edge MD. Tree-based QTL mapping with expected local genetic relatedness matrices. bioRxiv. 2023.04.07.536093. 2023.; Zhang BC, Biddanda A, Gunnarsson ÁF, Cooper F, Palamara PF. Biobank-scale inference of ancestral recombination graphs enables genealogical analysis of complex traits. Nat Genet. 2023:55(5):768–776.). As such, there has been significant interest in the field to investigate 2 main problems related to the ARG: (i) How can we estimate the ARG based on genomic data, and (ii) how can we extract information of past evolutionary processes from the ARG? In this perspective, we highlight 3 topics that pertain to these main issues: The development of computational innovations that enable the estimation of the ARG; remaining challenges in estimating the ARG; and methodological advances for deducing evolutionary forces and mechanisms using the ARG. This perspective serves to introduce the readers to the types of questions that can be explored using the ARG and to highlight some of the most pressing issues that must be addressed in order to make ARG-based inference an indispensable tool for evolutionary research. [ABSTRACT FROM AUTHOR]

Background: Although schistosomiasis is a public health issue in Mali, little is known about the parasite genetic profile. The purpose of this study was to analyze the genetic profile of the schistosomes of Schistosoma haematobium group in school-aged children in various sites in Mali. Methods: Urine samples were collected from 7 to 21 November 2021 and subjected to a filtration method for the presence S. haematobium eggs. The study took place in two schistosomiasis endemic villages (Fangouné Bamanan and Diakalèl), qualified as hotspots according to the World Health Organization (WHO) definition. Molecular genotyping on both Cox1 and ITS2/18S was used for eggs' taxonomic assignation. Results: A total of 970 miracidia were individually collected from 63 school-aged children and stored on Whatman FTA cards for molecular analysis. After genotyping 42.0% (353/840) and 58.0% (487/840) of miracidia revealed Schistosoma bovis and S. haematobium Cox1 profiles, respectively; 95.7 (885/925) and 4.3% (40/925) revealed S. haematobium and S. haematobium/S. curassoni profiles for ITS/18S genes, respectively. There was a significant difference in the Cox1 and ITS2/18S profile distribution according to the village (P < 0.0001). Overall, 45.6% (360/789) were hybrids, of which 72.0% (322/447) were from Diakalèl. Three hybrids' profiles (Sb/Sc_ShxSc with 2.3%; Sb/Sc_ShxSh with 40.5%; Sh_ShxSc with 2.8%) and one pure profile (Sh_ShxSh with 54.4%) were identified. Conclusion: Our findings show, for the first time to our knowledge, high prevalence of hybrid schistosomes in Mali. More studies are needed on population genetics of schistosomes at the human and animal interface to evaluate the parasite's gene flow and its consequences on epidemiology of the disease as well as the transmission to humans. [ABSTRACT FROM AUTHOR]

This study re-examines the linguistic phylogeny of the South Caucasian linguistic family (aka the Kartvelian linguistic family) and attempts to identify its Urheimat. We apply Bayesian phylogenetics to infer a dated phylogeny of the South Caucasian languages. We infer the Urheimat and the reasons for the split of the Kartvelian languages by taking into consideration (1) the past distribution ranges of wildlife elements whose names can be traced back to proto-Kartvelian roots, (2) the distribution ranges of past cultures and (3) the genetic variations of past and extant human populations. Our best-fit Bayesian phylogenetic model is in agreement with the widely accepted topology suggested by previous studies. However, in contrast to these studies, our model suggests earlier mean split dates, according to which the divergence between Svan and Karto-Zan occurred in the early Copper Age, while Georgian and Zan diverged in the early Iron Age. The split of Zan into Megrelian and Laz is widely attributed to the spread of Georgian and/or Georgian speakers in the seventh-eighth centuries CE. Our analyses place the Kartvelian Urheimat in an area that largely intersects the Colchis glacial refugium in the South Caucasus. The divergence of Kartvelian languages is strongly associated with differences in the rate of technological expansions in relation to landscape heterogeneity, as well as the emergence of state-run communities. Neolithic societies could not colonize dense forests, whereas Copper Age societies made limited progress in this regard, but not to the same degree of success achieved by Bronze and Iron Age societies. The paper also discusses the importance of glacial refugia in laying the foundation for linguistic families and where Indo-European languages might have originated. [ABSTRACT FROM AUTHOR]

Background: Although schistosomiasis is a public health issue in Mali, little is known about the parasite genetic profile. The purpose of this study was to analyze the genetic profile of the schistosomes of Schistosoma haematobium group in school-aged children in various sites in Mali. Methods: Urine samples were collected from 7 to 21 November 2021 and subjected to a filtration method for the presence S. haematobium eggs. The study took place in two schistosomiasis endemic villages (Fangouné Bamanan and Diakalèl), qualified as hotspots according to the World Health Organization (WHO) definition. Molecular genotyping on both Cox1 and ITS2/18S was used for eggs' taxonomic assignation. Results: A total of 970 miracidia were individually collected from 63 school-aged children and stored on Whatman FTA cards for molecular analysis. After genotyping 42.0% (353/840) and 58.0% (487/840) of miracidia revealed Schistosoma bovis and S. haematobium Cox1 profiles, respectively; 95.7 (885/925) and 4.3% (40/925) revealed S. haematobium and S. haematobium/S. curassoni profiles for ITS/18S genes, respectively. There was a significant difference in the Cox1 and ITS2/18S profile distribution according to the village (P < 0.0001). Overall, 45.6% (360/789) were hybrids, of which 72.0% (322/447) were from Diakalèl. Three hybrids' profiles (Sb/Sc_ShxSc with 2.3%; Sb/Sc_ShxSh with 40.5%; Sh_ShxSc with 2.8%) and one pure profile (Sh_ShxSh with 54.4%) were identified. Conclusion: Our findings show, for the first time to our knowledge, high prevalence of hybrid schistosomes in Mali. More studies are needed on population genetics of schistosomes at the human and animal interface to evaluate the parasite's gene flow and its consequences on epidemiology of the disease as well as the transmission to humans. [ABSTRACT FROM AUTHOR]

Mitochondrial DNA (mtDNA) is a small fraction of our hereditary material. However, this molecule has had an overwhelming presence in scientific research for decades until the arrival of high-throughput studies. Several appealing properties justify the application of mtDNA to understand how human populations are—from a genetic perspective—and how individuals exhibit phenotypes of biomedical importance. Here, I review the basics of mitochondrial studies with a focus on the dawn of the field, analysis methods and the connection between two sides of mitochondrial genetics: anthropological and biomedical. The particularities of mtDNA, with respect to inheritance pattern, evolutionary rate and dependence on the nuclear genome, explain the challenges of associating mtDNA composition and diseases. Finally, I consider the relevance of this single locus in the context of omics research. The present work may serve as a tribute to a tool that has provided important insights into the past and present of humankind. [ABSTRACT FROM AUTHOR]

The Nobel Assembly at the Karolinska Institute awarded the 2022 Nobel Prize in Physiology or Medicine to Svante Pääbo (Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany). This award acknowledged his discoveries about the genomes of extinct hominins (Neandertal man and the Denisovans), the molecular genetic insights of human origin and evolutionary history, and the understanding of phylogenetic relationships between archaic hominins and modern humans. The scientific advances included detection of Neandertal and Denisovan DNA carried by modern humans due to past admixture events, which in turn stimulated active research about the functional and phenotypic significance of such archaic ancestry on non-disease and disease phenotypic features in modern populations. In addition, comparative genomic studies started to delineate the genes and genetic regulation mechanisms that distinguish modern-day humans from the archaic hominins and our immediate ancestors, the anatomically modern humans. These breakthroughs allowed a more thorough understanding of ancestral and modern human population genetics, and propelled the take-off of human paleogenomics as a new scientific discipline in its own right. [ABSTRACT FROM AUTHOR]

As the chapter discusses, one of the most pressing questions, and an area of fruitful research, is how consumer genetics results contribute to essentialist beliefs about race and ethnicity. It would serve as an excellent primer text for undergraduate students, scholars who are adjacent to, but still outside of, genetics, or the general public trying to make sense of their consumer genetics results. What's DNA got to say about who you are?. [Extracted from the article]

Causal loss-of-function (LOF) variants for Mendelian and severe complex diseases are enriched in 'mutation intolerant' genes. We show how such observations can be interpreted in light of a model of mutation-selection balance and use the model to relate the pathogenic consequences of LOF mutations at present to their evolutionary fitness effects. To this end, we first infer posterior distributions for the fitness costs of LOF mutations in 17,318 autosomal and 679 X-linked genes from exome sequences in 56,855 individuals. Estimated fitness costs for the loss of a gene copy are typically above 1%; they tend to be largest for X-linked genes, whether or not they have a Y homolog, followed by autosomal genes and genes in the pseudoautosomal region. We compare inferred fitness effects for all possible de novo LOF mutations to those of de novo mutations identified in individuals diagnosed with one of six severe, complex diseases or developmental disorders. Probands carry an excess of mutations with estimated fitness effects above 10%; as we show by simulation, when sampled in the population, such highly deleterious mutations are typically only a couple of generations old. Moreover, the proportion of highly deleterious mutations carried by probands reflects the typical age of onset of the disease. The study design also has a discernible influence: a greater proportion of highly deleterious mutations is detected in pedigree than case-control studies, and for autism, in simplex than multiplex families and in female versus male probands. Thus, anchoring observations in human genetics to a population genetic model allows us to learn about the fitness effects of mutations identified by different mapping strategies and for different traits. [ABSTRACT FROM AUTHOR]

This paper examines two moments in the globalization of human genetics, focusing on the American University of Beirut as a site of interaction between American, European and Middle Eastern scientific actors and research subjects. In the interwar period, the establishment of clinical laboratories at AUB's medical school enabled the development of an informal large-scale programme to study human heredity through anthropometry and sero-anthropology. AUB's Middle Eastern students were trained in these techniques, and research results were disseminated locally in Arabic as well as in international scientific journals. In the post-war period, new technologies transformed human genetics into an internationally coordinated science with specialized laboratories. However, an attempt to establish such a lab at AUB during the 1960s ended in failure: the Anthropological Blood Grouping Laboratory functioned for only four years before closing. The American and British personalities who promoted the ABGL in Lebanon aimed to collect blood samples from across the region without committing to long-term relationships with local scientists and research subjects. As an 'outpost' for Western scientists, the ABGL embodied the neo-colonial structure of post-war human population genetics, both in its unfulfilled aspirations to serve metropolitan research agendas and in its marginalization of Middle Eastern scientists. [ABSTRACT FROM AUTHOR]

Abstract Sexual dimorphisms are widespread in animals and plants, for morphological as well as physiological traits. Understanding the genetic basis of sexual dimorphism and its evolution is crucial for understanding biological differences between the sexes. Genetic variants with sex‐antagonistic effects on fitness are expected to segregate in populations at the early phases of sexual dimorphism emergence. Detecting such variants is notoriously difficult, and the few genome‐scan methods employed so far have limited power and little specificity. Here, we propose a new framework to detect a signature of sexually antagonistic (SA) selection. We rely on trio datasets where sex‐biased transmission distortions can be directly tracked from parents to offspring, and identify signals of SA transmission distortions in genomic regions. We report the genomic location of six candidate regions detected in human populations as potentially under sexually antagonist selection. We find an enrichment of genes associated with embryonic development within these regions. Last, we highlight two candidate regions for SA selection in humans.

This is invisible to a two-level gene tree/species tree or host/symbiont reconciliation: in some cases looking at any combination of two levels can lead to miss an evolutionary scenario which can only be the most likely if the information from the three trees are considered together (Fig 6). Reconciliation in models with more than two levels A striking aspect of reconciliation is the common methodology handling different levels of organization: it is used for comparing domain and protein trees, gene and species trees, hosts and symbiont trees, population and geographic trees. It has been achieved with a species/gene/domain system, where genes evolve within the species tree with a DL model and domains evolve within the gene/species system with a DTL model, forbidding domain transfers between genes of two different species (Fig 5G) [[172]]. Horizontal gene transfer routes depend on multiple levels In https://en.wikipedia.org/wiki/endosymbiont insect systems, multiple occurrence of horizontal gene transfers have been identified, whether from host to symbiont, symbiont to host or symbiont to symbiont [[141]]. The evolution of this link appears as an additional level to species and gene trees, partly constrained by the gene/species tree reconciliation, partly evolving on its own, according to genome organization. [Extracted from the article]

Race science attributes differences in human populations to biology and genetics that reflect a hierarchy of human races with whiteness at its pinnacle. This article examining the history of race science and current family scholarship and practice contends that race science matters for family science. We discuss (1) white supremacy, the development of race science, and the eugenics movement in the U.S.; (2) racism, racialized experiences, and oppression of Black families in the U.S.; (3) the construction of whiteness in family science and re‐envisioning theories to make racism's impact visible; (4) racial reckonings for professional organizations; and (5) why race science matters for family science and a call to action. Clarity about the meaning of race can ensure that family science addresses white supremacy and racism embedded in scholarship, training, and practice, and promotes work that supports the well‐being of families that are most vulnerable and marginalized. [ABSTRACT FROM AUTHOR]

Chaim Sheba was one of Israel's most influential medical figures. An internist by training, Sheba was among the founding fathers of the Israeli military medical system and took part in shaping its unique local model. Between 1950 and 1952, he was the Health Ministry's Director General, and soon after was appointed Head of Tel-Hashomer Hospital. In addition, Sheba played an important part in establishing Barzilai Hospital, in Israel's southern region, and was also one of the chief founders of Tel-Aviv University's School of Medicine. Alongside his work as a doctor and hospital manager and his many public obligations and activities, Sheba conducted research on the genetics of different Jewish ethnic communities who emigrated to the nascent State of Israel. In this article, we focus on Sheba's biography and explore how his vision and relentless activity shaped Israel's health system. While Sheba's achievements are our focal point, we also discuss his professional disappointments and unfulfilled visions., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The article presents the discussion on descriptions of human biological variation in support of racism. Topics include considerable uncertainty regarding the genetics underlying the observed protein variation representing the best information available on genetic variation; and observations of racialized physical traits such as skin colour being representative of typical patterns of genetic diversity and divergence.

‘The Apportionment of Human Diversity’ stands as a noteworthy intervention, both for the field of human population genetics as well as in the annals of public communication of science. Despite the widespread uptake of Lewontin's conclusion that racial classification is of ‘virtually no genetic or taxonomic significance’, the biomedical research community continues to grapple with whether and how best to account for race in its work. Nowhere is this struggle more apparent than in the latest attempts to translate genetic associations with complex disease risk to clinical use in the form of polygenic risk scores, or PRS. In this perspective piece, we trace current challenges surrounding the appropriate development and clinical application of PRS in diverse patient cohorts to ongoing difficulties deciding which facets of population structure matter, and for what reasons, to human health. Despite numerous analytical innovations, there are reasons that emerge from Lewontin's work to remain sceptical that accounting for population structure in the context of polygenic risk estimation will allow us to more effectively identify and intervene on the significant health disparities which plague marginalized populations around the world. [ABSTRACT FROM AUTHOR]

A Y-STR polymorphism study is a convenient tool in molecular anthropology and forensic DNA analysis. Through standard ethical procedures, the proposed study explored the genetic scenario in male lineage in Madhya Pradesh, a central Indian state, by Y-STR genotyping and haplogroup studies. Five hundred and eleven unrelated male blood samples were directly amplified, and fragment separation was done using capillary electrophoresis to generate a Y-STR profile for 23 forensic relevant markers through PowerPlex® Y 23 multiplex system. The different statistical methods were applied for studying the forensic and genetics parameters. Subsequently, population comparison was performed by AMOVA, PCoA, and MDS plot, and Haplogroups were predicted with Whit Athey's haplogroup predictor tool. These data represented the potential value of the PowerPlex® Y-23 multiplex system for the forensic and human genetics application in the population of Madhya Pradesh, India. Simultaneously the Haplogroup analysis revealed information about the multi-geographic origin as well as multi-ethnic genetic affinities of the Madhya Pradesh population. [ABSTRACT FROM AUTHOR]

With the characteristics of low mutation rate, length variation and short amplicon size, insertion/deletion polymorphisms (InDels) have the advantages of both short tandem repeats (STRs) and single nucleotide polymorphisms (SNPs). Herein, people of two ethnicities from Hainan Island were genotyped for the first time using the Investigator DIPplex kit. We investigated the forensic parameters of the 30 InDels and the phylogenetic relationships among different populations. The accumulated powers of discrimination and powers of exclusion were 0.999 999 999 9646 and 0.9897 in the Hainan Han population and 0.999 999 999 9292 and 0.9861 in the Hainan Li population, respectively. Additionally, population comparisons among geographically, ethnically and linguistically diverse populations via cluster heatmap, multidimensional scaling, principal component analysis, phylogenetic tree and STRUCTURE analyses demonstrated that the Hainan Han population had genetic similarities to the other Han, She and Tujia populations, while the Hainan Li population had close genetic relationships to the Zhuang and Miao groups; both populations had a high degree of genetic differentiation from most Turkic-speaking populations. Aforementioned results suggested that the 30 autosomal InDels are highly polymorphic and informative, which are suitable for human identification and population genetics. Four hundred and forty-five Chinese individuals from two ethnicities (Hainan Han and Hainan Li) were firstly analyzed by 30 autosomal InDels included in the Investigator DIPplex panel. Forensic parameters of the 30 InDels in the two populations showed high polymorphism and universality for human identification purposes. The Investigator DIPplex panel had a certain capacity of differentiating intercontinental populations and different language populations. [ABSTRACT FROM AUTHOR]

Context The peopling of Europe by modern humans is a widely debated topic in the field of modern and ancient genomics. While several recent syntheses have focussed on this topic, little has been discussed about the genetic history of populations in the continent’s surrounding regions. Objective We explore genetic transformations in three key areas that played an essential role in the formation of the European genetic landscape through time, focussing on the periods spanning from the Epipalaeolithic/Mesolithic and up until the Iron Age. Methods We review published ancient genomic studies and integrate the associated data to provide a quantification and visualisation of major trends in the population histories of the Near East, the western Eurasian Steppe and North East Europe. Results We describe cross-regional as well as localised prehistoric demographic shifts and discuss potential research directions while highlighting geo-temporal gaps in the data. Conclusion In recent years, archaeogenetic studies have contributed to the understanding of human genetic diversity through time in regions located at the doorstep of Europe. Further studies focussing on these areas will allow for a better characterisation of genetic shifts and regionally-specific patterns of admixture across western Eurasia.

Currently available genetic tools effectively distinguish between different continental origins. However, North Eurasia, which constitutes one-third of the world's largest continent, remains severely underrepresented. The dataset used in this study represents 266 populations from 12 North Eurasian countries, including most of the ethnic diversity across Russia's vast territory. A total of 1,883 samples were genotyped using the Illumina Infinium Omni5Exome-4 v1.3 BeadChip. Three principal components were computed for the entire dataset using three iterations for outlier removal. It allowed the merging of 266 populations into larger groups while maintaining intragroup homogeneity, so 29 ethnic geographic groups were formed that were genetically distinguishable enough to trace individual ancestry. Several feature selection methods, including the random forest algorithm, were tested to estimate the number of genetic markers needed to differentiate between the groups; 5,229 ancestry-informative SNPs were selected. We tested various classifiers supporting multiple classes and output values for each class that could be interpreted as probabilities. The logistic regression was chosen as the best mathematical model for predicting ancestral populations. The machine learning algorithm for inferring an ancestral ethnic geographic group was implemented in the original software "Homeland" fitted with the interface module, the prediction module, and the cartographic module. Examples of geographic maps showing the likelihood of geographic ancestry for individuals from different regions of North Eurasia are provided. Validating methods show that the highest number of ethnic geographic group predictions with almost absolute accuracy and sensitivity was observed for South and Central Siberia, Far East, and Kamchatka. The total accuracy of prediction of one of 29 ethnic geographic groups reached 71%. The proposed method can be employed to predict ancestries from the populations of Russia and its neighbor states. It can be used for the needs of forensic science and genetic genealogy. [ABSTRACT FROM AUTHOR]

In 2014, 157 years after the Sepoy Mutiny of 1857, several unidentified human skeletons were discovered in an abandoned well at Ajnala, Punjab. The most prevailing hypothesis suggested them as Indian soldiers who mutinied during the Indian uprising of 1857. However, there is an intense debate on their geographic affinity. Therefore, to pinpoint their area of origin, we have successfully isolated DNA from cementum-rich material of 50 good-quality random teeth samples and analyzed mtDNA haplogroups. In addition to that, we analyzed 85 individuals for oxygen isotopes (δ18O values). The mtDNA haplogroup distribution and clustering pattern rejected the local ancestry and indicated their genetic link with the populations living east of Punjab. In addition, the oxygen isotope analysis (δ18O values) from archaeological skeletal remains corroborated the molecular data and suggested the closest possible geographical affinity of these skeletal remains toward the eastern part of India, largely covering the Gangetic plain region. The data generated from this study are expected to expand our understanding of the ancestry and population affinity of martyr soldiers. [ABSTRACT FROM AUTHOR]

Admixture has been a pervasive phenomenon in human history, extensively shaping the patterns of population genetic diversity. There is increasing evidence to suggest that admixture can also facilitate genetic adaptation to local environments, i.e., admixed populations acquire beneficial mutations from source populations, a process that we refer to as "adaptive admixture." However, the role of adaptive admixture in human evolution and the power to detect it remain poorly characterized. Here, we use extensive computer simulations to evaluate the power of several neutrality statistics to detect natural selection in the admixed population, assuming multiple admixture scenarios. We show that statistics based on admixture proportions, F adm and LAD, show high power to detect mutations that are beneficial in the admixed population, whereas other statistics, including iHS and F ST , falsely detect neutral mutations that have been selected in the source populations only. By combining F adm and LAD into a single, powerful statistic, we scanned the genomes of 15 worldwide, admixed populations for signatures of adaptive admixture. We confirm that lactase persistence and resistance to malaria have been under adaptive admixture in West Africans and in Malagasy, North Africans, and South Asians, respectively. Our approach also uncovers other cases of adaptive admixture, including APOL1 in Fulani nomads and PKN2 in East Indonesians, involved in resistance to infection and metabolism, respectively. Collectively, our study provides evidence that adaptive admixture has occurred in human populations whose genetic history is characterized by periods of isolation and spatial expansions resulting in increased gene flow. [ABSTRACT FROM AUTHOR]

Sexual dimorphisms are widespread in animals and plants, for morphological as well as physiological traits. Understanding the genetic basis of sexual dimorphism and its evolution is crucial for understanding biological differences between the sexes. Genetic variants with sex‐antagonistic effects on fitness are expected to segregate in populations at the early phases of sexual dimorphism emergence. Detecting such variants is notoriously difficult, and the few genome‐scan methods employed so far have limited power and little specificity. Here, we propose a new framework to detect a signature of sexually antagonistic (SA) selection. We rely on trio datasets where sex‐biased transmission distortions can be directly tracked from parents to offspring, and identify signals of SA transmission distortions in genomic regions. We report the genomic location of six candidate regions detected in human populations as potentially under sexually antagonist selection. We find an enrichment of genes associated with embryonic development within these regions. Last, we highlight two candidate regions for SA selection in humans. [ABSTRACT FROM AUTHOR]

Island Southeast Asia (ISEA) and Oceania host one of the world's richest assemblages of human phenotypic, linguistic, and cultural diversity. Despite this, the region's male genetic lineages are globally among the last to remain unresolved. We compiled ∼9.7 Mb of Y chromosome (chrY) sequence from a diverse sample of over 380 men from this region, including 152 first reported here. The granularity of this data set allows us to fully resolve and date the regional chrY phylogeny. This new high-resolution tree confirms two main population bursts: multiple rapid diversifications following the region's initial settlement ∼50 kya, and extensive expansions <6 kya. Notably, ∼40–25 kya the deep rooting local lineages of C-M130, M-P256, and S-B254 show almost no further branching events in ISEA, New Guinea, and Australia, matching a similar pause in diversification seen in maternal mitochondrial DNA lineages. The main local lineages start diversifying ∼25 kya, at the time of the last glacial maximum. This improved chrY topology highlights localized events with important historical implications, including pre-Holocene contact between Mainland and ISEA, potential interactions between Australia and the Papuan world, and a sustained period of diversification following the flooding of the ancient Sunda and Sahul continents as the insular landscape observed today formed. The high-resolution phylogeny of the chrY presented here thus enables a detailed exploration of past isolation, interaction, and change in one of the world's least understood regions. [ABSTRACT FROM AUTHOR]

Currently available genetic tools effectively distinguish between different continental origins. However, North Eurasia, which constitutes one-third of the world’s largest continent, remains severely underrepresented. The dataset used in this study represents 266 populations from 12 North Eurasian countries, including most of the ethnic diversity across Russia’s vast territory. A total of 1,883 samples were genotyped using the Illumina Infinium Omni5Exome-4 v1.3 BeadChip. Three principal components were computed for the entire dataset using three iterations for outlier removal. It allowed the merging of 266 populations into larger groups while maintaining intragroup homogeneity, so 29 ethnic geographic groups were formed that were genetically distinguishable enough to trace individual ancestry. Several feature selection methods, including the random forest algorithm, were tested to estimate the number of genetic markers needed to differentiate between the groups; 5,229 ancestry-informative SNPs were selected. We tested various classifiers supporting multiple classes and output values for each class that could be interpreted as probabilities. The logistic regression was chosen as the best mathematical model for predicting ancestral populations. The machine learning algorithm for inferring an ancestral ethnic geographic group was implemented in the original software “Homeland” fitted with the interface module, the prediction module, and the cartographic module. Examples of geographic maps showing the likelihood of geographic ancestry for individuals from different regions of North Eurasia are provided. Validating methods show that the highest number of ethnic geographic group predictions with almost absolute accuracy and sensitivity was observed for South and Central Siberia, Far East, and Kamchatka. The total accuracy of prediction of one of 29 ethnic geographic groups reached 71%. The proposed method can be employed to predict ancestries from the populations of Russia and its neighbor states. It can be used for the needs of forensic science and genetic genealogy.

In 2014, 157 years after the Sepoy Mutiny of 1857, several unidentified human skeletons were discovered in an abandoned well at Ajnala, Punjab. The most prevailing hypothesis suggested them as Indian soldiers who mutinied during the Indian uprising of 1857. However, there is an intense debate on their geographic affinity. Therefore, to pinpoint their area of origin, we have successfully isolated DNA from cementum-rich material of 50 good-quality random teeth samples and analyzed mtDNA haplogroups. In addition to that, we analyzed 85 individuals for oxygen isotopes (δ18O values). The mtDNA haplogroup distribution and clustering pattern rejected the local ancestry and indicated their genetic link with the populations living east of Punjab. In addition, the oxygen isotope analysis (δ18O values) from archaeological skeletal remains corroborated the molecular data and suggested the closest possible geographical affinity of these skeletal remains toward the eastern part of India, largely covering the Gangetic plain region. The data generated from this study are expected to expand our understanding of the ancestry and population affinity of martyr soldiers.

Weiner's proposal was adopted and, with Weiner as its international Convener (Director), the "The Human Adaptability" (HA) section became a component of the IBP. Patterned on the highly successful International Geophysical year (IGY, 1957), in 1962, the International Council of Scientific Unions met in Switzerland and established the International Biological Programme (IBP). Weiner's and Lourie's book on methods (1969, I Human Biology: A Guide to Field Methods i , Blackwell, Oxford) established standardized methods that were employed by about 260 active research projects from 40 countries. [Extracted from the article]

Projection analysis is a tool that extracts information from the joint allele frequency spectrum to better understand the relationship between two populations. In projection analysis, a test genome is compared to a set of genomes from a reference population. The projection's shape depends on the historical relationship of the test genome's population to the reference population. Here, we explore in greater depth the effects on the projection when ancient samples are included in the analysis. First, we conduct a series of simulations in which the ancient sample is directly ancestral to a present-day population (one-population model), or the ancient sample is ancestral to a sister population that diverged before the time of sampling (two-population model). We find that there are characteristic differences between the projections for the one-population and two-population models, which indicate that the projection can be used to determine whether a test genome is directly ancestral to a present-day population or not. Second, we compute projections for several published ancient genomes. We compare two Neanderthals and three ancient human genomes to European, Han Chinese and Yoruba reference panels. We use a previously constructed demographic model and insert these five ancient genomes to assess how well the observed projections are recovered.

Genetic variation in the human gut microbiome is responsible for conferring a number of crucial phenotypes like the ability to digest food and metabolize drugs. Yet, our understanding of how this variation arises and is maintained remains relatively poor. Thus, the microbiome remains a largely untapped resource, as the large number of coexisting species in the microbiome presents a unique opportunity to compare and contrast evolutionary processes across species to identify universal trends and deviations. Here we outline features of the human gut microbiome that, while not unique in isolation, as an assemblage make it a system with unparalleled potential for comparative population genomics studies. We consciously take a broad view of comparative population genetics, emphasizing how sampling a large number of species allows researchers to identify universal evolutionary dynamics in addition to new genes, which can then be leveraged to identify exceptional species that deviate from general patterns. To highlight the potential power of comparative population genetics in the microbiome, we reanalyze patterns of purifying selection across ∼40 prevalent species in the human gut microbiome to identify intriguing trends which highlight functional categories in the microbiome that may be under more or less constraint. [ABSTRACT FROM AUTHOR]

Race in science, medicine, and technology A rich body of literature exists on race in the biosciences, biomedicine, and technology. Moving beyond the lab is not moving outside of laboratory science practices or outside of Western science. So, moving beyond the lab is a move to decentre the laboratory as the place of knowledge and instead pursue a commitment to decolonise knowledge practices, even if the knowledge at stake is biomedicine or genetics. Genetic knowledge is paradigmatically laboratory knowledge, and yet its power does not rise or fall on scientific truth claims situated there. [Extracted from the article]