abstract: Migraine is a primary headache disorder with neurovascular involvement. Migraine with aura is a subtype that accounts for approximately 15%–40% of all migraine cases. Several studies have shown that the global prevalence of migraine varies depending on the population studied. The population of Buenos Aires Province has an admixed genetic background. Several genetic association studies on migraine have been reported; however, most of them were conducted in cohorts of European ancestry, introducing a bias that overlooks global population diversity. DNA was extracted from 310 individuals (153 cases and 157 controls). Genotypes were determined using allele-specific polymerase chain reaction and polymerase chain reaction–restriction fragment length polymorphism techniques for the following polymorphisms: rs2075968 ( PRDM16 ), rs12134493 ( TSPAN2 ), rs10166942 ( TRPM8 ), rs10456100 ( KCNK5 ), rs4910165 ( IRAG1 ), rs11031122 ( MPPED2 ), rs11172113 ( LRP1 ), and rs6081613 ( SLC24A3 ). A case-control analysis was conducted using logistic regression models. All markers were in Hardy-Weinberg equilibrium in the case group. In the control group, however, rs4910165 ( IRAG1 ) deviated from equilibrium and was therefore excluded from the association analysis ( p = .0032). Although codominant and dominant models including all markers simultaneously did not yield significant results, in a single-marker analysis, a trend was suggested for the AA genotype of rs2075968 ( PRDM16 ) under a codominant model ( p = .027, OR = 0.42, 95% CI = 0.20–0.91). These exploratory findings suggest a potential protective role of the AA genotype of rs2075968 ( PRDM16 ) in migraine with aura in the Buenos Aires Province population. Further studies involving additional PRDM16 variants and larger sample sizes are needed to confirm and expand upon these results.
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most prevalent enzyme deficiency of human erythrocytes, affecting more than 500 million people globally. G6PD deficiency is the most com- mon hemolytic X-linked genetic disease, which shows a higher prevalence rate in the malaria-endemic population. This review essay aims to examine the overall frequency of G6PD deficiency in the Indian population using systemic review, with a special emphasis on the differential prevalence rate across populations. PubMed, Google Scholar, and ScienceDirect databases were searched to examine the scientific studies focusing on the prevalence of G6PD deficiency among Indian populations. A total of 32 studies were selected after following several inclusion-exclusion criteria, which comprised a total of 115,300 participants. It is observed that the G6PD deficiency is higher among males than females, which is expected as this enzymopathy is caused by inherited mutations of the X-linked gene G6PD. Moreover, the disorder is considerably greater among populations that prefer consanguineal and endogamous marriages, such as Parsi, Muslim, and tribal populations, as compared with nontribal and caste populations. Hence, culturally based marriage practices may help to explain differences in the frequency of this hemolytic genetic disorder among Indian populations.
ABSTRACT: Sickle cell anemia occurs in individuals who are homozygous for the sickle hemoglobin (HbS) allele. The haplotypes of the HbS alleles can be traditionally ascertained through the analysis of five to eight informative restriction fragment length polymorphisms within the HBB gene cluster, defining the five major HbS haplotypes, commonly referred to as Bantu or Central African Republic (CAR), Benin (BEN), Cameroon (CAM), Senegal (SEN), and Arab-Indian. In a recent study, it was suggested that four single nucleotide polymorphisms (SNPs)—rs3834466, rs28440105, rs10128556, and rs968857—are sufficient to characterize most of the HbS haplotypes. In the present study, we investigated the HbS haplotypes in a population sample from São Tomé e Príncipe (Central Africa) by analyzing this set of four SNPs. Additionally, we included the HBG2 rs7482144 (−158C>T) SNP, which is commonly used in the classical HbS haplotype classification, to compare the HbS haplotypes derived from the two different plex systems. Blood samples of 50 heterozygous (HbAS), nine homozygous (HbSS), and three normal HbAA individuals were engaged in this study. Genotyping was performed by the polymerase chain reaction–restriction fragment length polymorphism method. Haplotypes were derived using the Arlequin software. In the 4-plex system, seven different haplotypes were inferred among the 68 HbS chromosomes, corresponding to CAR, 36.8%; BEN, 25.0%; CAM, 13.2%; SEN, 11.8%; and three different sets of unknown HbS haplotypes, 11.4%. The further inclusion of rs7482144 (XmnI) led to the inference of a total of eight distinct HbS haplotypes as follows: CAR, 36.8%; BEN, 25.0%; CAM, 13.2%; SEN, 8.8%; and four different clusters of unknown HbS haplotypes, 16.2%. Using only the nine homozygous HbSS individuals, the same five different haplotypes were identified for both systems, with all common haplotypes occurring at equal frequencies: CAR, 27.8%; BEN, 38.9%; CAM, 16.7%; and SEN, 11.1%. One atypical haplotype was identified at a frequency of 5.6%. Our findings suggest that the 4-plex system may not be entirely accurate in identifying the SEN haplotype when considering heterozygous individuals for the HbS allele in the study population. Additionally, the haplotype background of HbS observed in the S. Tomean population provided further insights compared with previous reports.
abstract: Genetic and archaeological studies indicate that the American continent has undergone multiple waves of human migration, shaping a complex population genetic structure comprising three major ethnic groups—Native American, European, and African—unevenly distributed across the continent. In this study, we examined MAPT (17q21.31) haplotype and subhaplotype frequencies by analyzing two single nucleotide polymorphism markers (rs10514879 and rs199451) in three South American groups from distinct countries: Waorani (Ecuadorian Amazon), Jujuy (northwestern Argentina), and Afro-Colombian (northwestern Colombia). To broaden the scope, we also genotyped four short tandem repeats within the 17q21.31 chromosomal region and compiled H2 haplotype and subhaplotype frequency data for 97 worldwide populations (Africa: 26; Asia: 37; Europe: 19; America: 15). We used the publicly available genome-wide databases 1000G and ALFRED. Genetic heterogeneity among population clusters, classified by geographic region, was examined by hierarchical analysis of molecular variance. Likewise, we explored genetic affinities between the Waorani, Afro-Colombian, and Jujuy samples and worldwide collections using factorial correspondence analysis. The H1 haplotype predominated in all study populations. Notably, H2 varied among them: In Afro-Colombians, H2 was found at a frequency of 0.058, with equal representation of subhaplotypes H2’ and H2D. Among Native American groups (Waorani and Jujuy), the H2 haplotype was virtually absent, with only H2D detected in Jujuy at a very low frequency (0.007). Analysis of a set of short tandem repeats from the MAPT region identified distinct genetic features in Native American groups, characterized by markedly low heterozygosity. Waorani and Karitiana exhibited strikingly low genetic diversity, reflecting a significant degree of population isolation and, consequently, a potentially strong impact of genetic drift. In summary, our analyses demonstrate the utility of MAPT haplotypes in detecting the effects of population isolation, genetic drift, and admixture on the gene pool of the South American samples examined. MAPT haplotypes may serve as reliable lineage markers, given their ability to differentiate ethnic groups and trace ancestral chromosomes. They have proved to be an informative and cost-effective tool for exploring ancestry, geographic origins, and demographic history in anthropological studies.
Forensic anthropologists working in university laboratories are often curators of long-term unidentified human remains cases. Here, we review how and why anthropologists can effectively move toward case resolution by drawing on literature and collaborative best practices from the field of social work. Borrowing from the National Association of Social Workers standards for case management, we detail five standards that can be effectively followed during the forensic anthropological case investigation to ensure culturally sensitive and victim-centered approaches to human identification. While the field of forensic anthropology has its own professional standards developed through a consensus body and shared governance, these standards cannot address all the issues inherent in doing long-term unidentified remains casework in academic laboratories. By borrowing useful standardized National Association of Social Workers procedures (with their focus on improving the lives of living people), we outline how we can improve standards of care and service for deceased individuals in our laboratories. Using case studies from anthropology laboratories in the U.S. Northeast, Midwest, and West that are directed by anthropologists tasked with identification and/or curation of archaeological, historical, anatomical, and forensic cases, we offer collaborative strategies for resource-constrained institutions. As current debates about bodily autonomy, antemortem consent, and ethical treatment of the dead continue to (re)define how anthropologists interact with the individual remains in their care, we offer one potential path forward by exploring how our work can be more deeply understood and enacted by positioning ourselves as “social workers for the deceased.”
The Central Plains region of China was one of the earliest domestication hubs for broomcorn and foxtail millet. This region nurtured rich archaeological cultures and experienced extensive interactions with neighboring populations during the Neolithic period. However, limited genomic research has hindered a clear understanding of the maternal genetic structure and population expansion history in this era. Here, we report 12 complete mitochondrial genomes from individuals of the Yanzhai site population from the Henan Province of China during the Longshan culture period, revealing a high level of maternal genetic diversity. The close genetic distance between these individuals and ancient populations from the Yellow River basin highlights the maternal genetic continuity since the late Neolithic period. Furthermore, our research uncovers multiple population expansion events driven by various factors, which may have contributed to the genetic composition of modern East Asian populations. In summary, our study provides a new perspective on the genetic origins and demographic dynamics of the Central Plains region during the late Neolithic period.
Dermatoglyphic studies of traditional rainforest hunter-gatherers (RHG) have a long history, but as yet no one has synthesized the available data to develop a coherent picture of RHG relationships to one another and to their agricultural (AGR) neighbors. This has been due in part to absence of comparable data, which has now been remedied by the late H. Brehme of Freiburg University, who counted ridges and classified patterns on existing prints, mostly collected in the early 20th century. Thus, analyses of dermatoglyphic prints from most African RHG groups, done in the same way by the same observer, now exist. The present analysis uses finger ridge counts to examine the structure of RHG and AGR populations. Eastern RHG and some AGR samples come from the eastern Democratic Republic of the Congo, some eastern AGR samples are from Kenya, and western RHG and AGR samples come from Cameroon and adjacent countries. Statistical procedures include analysis of variance (ANOVA), multivariate analysis of variance (MANOVA), analysis of covariance, and canonical variates obtained from the discriminant procedure. The relationship of ridge counts to adult stature was also examined. Eastern and western RHG are clearly differentiated on ridge counts. Eastern RHG are differentiated from their AGR neighbors by virtue of very low ridge counts, but western RHG have higher ridge counts, more in line with their AGR neighbors. MANOVA results reveal significant variation among groups and sexes, as well as variation among groups in sex dimorphism. Beyond the marked differences between eastern and western RHG, the western AGR show a certain cohesion, but eastern AGR are highly dispersed. Variation in sex dimorphism involves primarily eastern and western AGR groups. Ridge counts also correlate with stature, suggesting that short stature has prenatal origins. The general conclusion is that ridge-count variation supports a difference between eastern and western RHG seen in cranial morphology and genetics. The unanswered question is why eastern RHG, with the lowest ridge counts in the world, are so differentiated. Variation in sex dimorphism, especially among the AGR neighbors, implies different responses to prenatal hormones. Ridge counts demonstrate variation in prenatal development, which is still poorly understood. Genes influencing limb and digit development have been identified, which along with postnatal anthropometric and disease associations provide a basis for future development and testing of hypotheses.
The genetic variant rs10974944 (C>G) in the JAK2 gene is associated with a higher risk of myeloproliferative neoplasms (MPNs) by increasing the probability of the somatic mutation V617F in the JAK2 protein. For this reason, we evaluated the distribution of rs10974944 in Mexican populations, including published data from association studies in worldwide populations. We analyzed five Mestizo (admixed; n = 200) and four Native American (n = 200) population samples from Mexico, representing the northern, central, western, and southern regions of the country, genotyping rs10974944 by quantitative PCR using Taqman probes. Allele and genotype frequencies were estimated in each population sample. The wild-type allele C, the homozygous C/C, and the heterozygous C/G variants were the most frequent in all Mexican populations, and the genotype distribution in all samples was in Hardy-Weinberg equilibrium. Interestingly, genetic distances clustered most of the worldwide patient samples, including Tarahumaras and Mayas, which differed from Mexican and control samples. Although higher genetic susceptibility to MPNs could be predicted in these Native American populations, the homogeneous allele distribution among Mexican and worldwide control populations warrants analysis of further genetic and nongenetic factors. In sum, although worldwide population samples displayed homogeneous distribution for rs10974944 , genetic clustering of worldwide patients supports the claimed association with MPNs.
abstract: Studies of modern and ancient DNA (aDNA) have substantially improved our understanding of the early history of human populations. Despite advances in whole-genome sequencing technologies, present studies of aDNA are largely based on a panel of preselected genomic variants; thus, valuable genetic information in aDNA should be further explored. This study analyzed genotype data from 19 ancient and 16 modern high-coverage shotgun human genomes. We used modern populations from the 1000 Genomes Project and the Human Genome Diversity Project as reference populations and selected single-nucleotide polymorphisms (SNPs) that were polymorphic in one reference population and monomorphic in the others. Ancestral spectrum analyses based on the population-specific SNPs were conducted on the 19 aDNA and 16 modern DNA samples to determine their coancestries with modern reference populations. These analyses effectively revealed the genetic affinity between aDNA and modern populations, which is also true for modern DNA. The results for the 11 aDNA samples with expected transition-to-transversion ratios agree with previous analyses; the 8 aDNA samples with excessive transition-to-transversion ratios revealed ancestral spectra indicative of a high level of DNA damage that cannot be fully explained by postmortem cytosine deamination. Additional biochemistry or bioinformatics treatments seem necessary for the meaningful study of such aDNA.
abstract: This special issue of Human Biology , titled “Perspectives in Embodiment Theory,” brings together researchers who use a variety of lenses within the field of human biology to celebrate the plurality and wide applicability of embodiment. This special issue works to cross disciplinary boundaries to create more nuanced understandings of embodiment, plasticity, and experience in humans.
Interferon-induced transmembrane protein 3 (IFITM3) plays a substantial role in the immune system by repressing viral entry into host cells and restricting virus replication. Recent research suggests that specific polymorphisms of the IFITM3 gene, rs34481144 and rs12252, contribute to susceptibility to viral infections across populations dependent on their population frequencies, which needs further clarification. This population-based study determined the prevalence of two regulator SNPs in the Turkish population and evaluated genotype and allele frequencies in individuals stratified into groups based on a pilot survey conducted during the COVID-19 pandemic. Tetra-Primer Arms PCR assays and Sanger sequencing methods were used to genotype rs34481144 and rs12252; all participants (n = 200) answered a questionnaire on individual experiences (e.g., disease severity, vaccine side effects) during the COVID-19 pandemic. Distributions of genotype frequencies and pairwise linkage disequilibrium correlations were calculated and compared to publicly available data from worldwide populations. The minor allele frequencies for rs12252-G and rs34481144-T were 0.128 and 0.324, respectively, in the total sample. Our preliminary survey data gave no concrete evidence of a correlation between the analyzed SNPs and COVID-19 severity or vaccine side effects yet pinpointed a trend for an association between rs12252-G and symptom burdens, which merits further investigation. Overall, our results present genotype and allele distributions of two IFITM3 polymorphisms in the Turkish population and provide preliminary data on previously suggested correlations of genotype with COVID-19 in our population.
Population genetic studies have shown that the Bosnian-Herzegovinian (B&H) population is a part of the European gene pool, but there has been limited information on the genetic structure of ancient B&H populations. This study aimed to determine the frequency and distribution of mitochondrial DNA (mtDNA) haplogroups for a medieval Bosnian population. Thirty-four samples, excavated from medieval necropolises located within the borders of medieval Bosnia, were analyzed. Sequencing of the mtDNA hypervariable segment 1 (HVS1) region and RFLP analysis were performed for haplogroup determination. All 32 samples were identified as haplogroup H, with subhaplogroups H2a and H5 in 30 and 2 samples, respectively. The frequency of the H haplogroup was significantly different between the studied samples and previous studies of contemporary B&H populations, where the H haplogroup frequency was approximately half that of the ancient population studied here. A significant difference in H haplogroup frequency compared with other medieval populations outside of Bosnia was also observed: the ancient B&H population is most similar to ancient Italians. These results provide insight into the mitochondrial landscape of populations that inhabited the territory of present-day Bosnia and Herzegovina in the Middle Ages. Our study reveals that inhabitants of medieval Bosnia carried genetic lineages that exist today in B&H populations, suggesting continuity of mtDNA haplogroups over a long period of time, regardless of various historical demographic events that shaped the genetic structure of the modern B&H population.
The human Y-chromosome haplogroup E-M81 is predominant in northwestern Africa and almost absent elsewhere, except for the Iberian Peninsula. In the present study, we investigated the internal branches of E-M81 (E1b1b1b1a) in 29 unrelated men from mainland Portugal. All individuals sampled carried the derived allele for the marker M183 (E1b1b1b1a1), and all but two had the derived allele for the marker SM001. Eleven individuals carried the derived allele for the marker Z5009 (E1b1b1b1a1c), and 16 were assigned to the paragroup E-SM001*(xZ5009, PF6794, CTS12227, M165, M5043). Median-joining networks based on seven Y-chromosome short tandem repeats (DYS19, DYS389I, DYS389II, DYS390, DYS391, DYS392, and DYS393) showed 14 different haplotypes, revealing a clear star-like structure, with the common central haplotype distributed by the three different subclades identified (M183*, SM001*, and Z5009) encompassing the typical Maghrebin core haplotype in northern African populations. The relatively high frequency of the E-M81 lineage in mainland Portugal supports a North African Y-chromosomal contribution that may have occurred during the Islamic period in the country.
The genetic variant rs10974944 (C>G) in the JAK2 gene is associated with a higher risk of myeloproliferative neoplasms (MPNs) by increasing the probability of the somatic mutation V617F in the JAK2 protein. For this reason, we evaluated the distribution of rs10974944 in Mexican populations, including published data from association studies in worldwide populations. We analyzed five Mestizo (admixed; n = 200) and four Native American (n = 200) population samples from Mexico, representing the northern, central, western, and southern regions of the country, genotyping rs10974944 by quantitative PCR using Taqman probes. Allele and genotype frequencies were estimated in each population sample. The wild-type allele C, the homozygous C/C, and the heterozygous C/G variants were the most frequent in all Mexican populations, and the genotype distribution in all samples was in Hardy-Weinberg equilibrium. Interestingly, genetic distances clustered most of the worldwide patient samples, including Tarahumaras and Mayas, which differed from Mexican and control samples. Although higher genetic susceptibility to MPNs could be predicted in these Native American populations, the homogeneous allele distribution among Mexican and worldwide control populations warrants analysis of further genetic and nongenetic factors. In sum, although worldwide population samples displayed homogeneous distribution for rs10974944 , genetic clustering of worldwide patients supports the claimed association with MPNs.
Understanding gene variations in people living under extreme conditions has the potential of curing diseases caused by exposure to heat, cold, fatty diets, hypoxia, and pathogens. One candidate gene associated with heat resistance is ACE1, encoding angiotensin-converting enzyme 1. Associations have also been made between cold resistance or fatty diets and polymorphisms of several genes, including ACTN3, encoding alpha-actinin-3, and CPTIA, encoding carnitine palmitoyltransferase 1A. A prominent role in resistance to hypoxia has been recognized for polymorphisms of EPAS1, encoding endothelial PAS domain protein 1, and EGLN1, encoding Egl-9 family hypoxia inducible factor 1. Variants conferring human resistance to pathogens include HBB, encoding hemoglobin subunit beta, and ACE2, encoding angiotensin-converting enzyme 2. Genetic knowledge concerning such diseases as malaria and conditions such as hypoxia should continue to promote advances in gene therapy.
Abstract: The Yi people in southwestern China are renowned for their unique history, social structure, and customs. However, due to extensive genetic admixture during their formative period, the early origin and evolutionary trajectory of the Yi people remain unclear. In this study, we identify four paternal founder lineages of Yi people and generate a highly revised phylogenetic tree for these four lineages with 66 sequences. Furthermore, the geographic distribution of four lineages within China is summarized, based on 465 individuals identified among 60,009 Chinese males. The divergence topology indicates that among all Tibeto-Burman-speaking populations, the Naxi, Bai, and Burmese populations exhibit the closest genetic affinity with the Yi people. The distribution of four founder lineages shows similar higher frequency in the Yunnan-Guizhou Plateau, the center of the Yi people’s inhabited area. We conduct an in-depth analysis of the possible origin, migration patterns, and roles of these four components in the demographic history of the Yi people.
Chimerism is a rare biological phenomenon in which an individual harbors two or more genetically distinct cell lines, typically resulting from the fusion of two embryos or from twin-to-twin cell transfer in utero. Though often asymptomatic, chimerism can have significant implications for fertility, development, and immunological compatibility. Its true prevalence remains unknown due to frequent underdiagnosis, especially in the absence of phenotypic clues. Recurrent pregnancy loss, defined as the occurrence of two or more consecutive miscarriages, is often attributed to chromosomal abnormalities, uterine malformations, thrombophilia, or immune dysfunction. Paternal contributions, particularly involving rare genetic anomalies, are far less investigated. Here, we report a unique case of a male with 46,XX/46,XY chimerism, discovered during the evaluation of a couple with three consecutive pregnancy losses. We hypothesize that the presence of 46,XXgerm cells in the testes might give rise to epigenetically abnormal spermatozoa, which could disrupt embryonic development through faulty genomic imprinting. Although causality cannot be confirmed in the absence of functional assays, we propose that chimerism might represent an undenecognized and understudied cause of recurrent miscarriage. This case highlights the need to further explore rare paternal genetic configurations in the context of unexplained recurrent pregnancy loss.
Pakistan is among the countries with the highest prevalence of consanguineous unions, with reported rates ranging between 55% and 65%. This high level of consanguinity contributes significantly to the burden of recessive genetic disorders. The Chitrali population, an isolated community residing in the Hindu Kush mountains of northwestern Pakistan, exhibits distinct genetic and cultural characteristics. This study aimed to assess the prevalence and patterns of consanguineous unions within this population. A random sample of 993 individuals from Chitral was recruited between January 2023 and December 2024 through visits to public venues and household surveys. The consanguinity rate and inbreeding coefficient were calculated, and their associations with various biodemographic variables were analyzed. Descriptive statistics and logistic regression models were employed for data analysis. The overall consanguinity rate was found to be 12%, with an estimated inbreeding coefficient of 0.0052. Interestingly, consanguinity showed a trend toward higher prevalence with increased literacy and exhibited a positive association with higher socioeconomic status. The Chitrali population exhibits the lowest reported rate of consanguinity among Pakistani populations. This community has retained diverse marital practices that differ markedly from those of neighboring populations. Contributing factors to the low consanguinity rate may include geographic isolation, low population density, family structures that discourage intrahousehold cousin marriages, and minimal tribal conflict or land-related disputes. These dynamics suggest that, despite its genetic distinctiveness, the Chitrali population may have a lower burden of the recessive disorders commonly observed in more inbred populations across Pakistan.
The apolipoprotein E ( APOE ) ε4 allele is a major genetic risk factor for Alzheimer’s disease and cardio- vascular risk. This study analyzes the distribution of APOE alleles in 143 patients from a Mexican population based in Mexico City. The ε3 allele was the most prevalent (82.9%), followed by ε4 (12.5%) and ε2 (4.5%). Notably, the APOE 3/4 genotype, associated with increased risk for Alzheimer’s and cardiovascular disease, was observed in 21.0% of the cohort, while the APOE 4/4 genotype, representing the highest genetic risk for both conditions, was rare (2.1%). The APOE 2/2 genotype, linked to type III dysbetalipoproteinemia, was absent in this population. These findings align with global trends but highlight unique aspects of the Mexican population, such as the lower prevalence of APOE 4 compared with Northern European and African populations. This study underscores the importance of population-specific genetic screening for personalized medicine, particularly in managing Alzheimer’s and cardiovascular risks. The results provide valuable insights into the genetic landscape of APOE in Mexico City, contributing to the growing body of knowledge on APOE allele distribution and its implications for disease prevention and management in Latin America.
