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Background: alpha-Synuclein is involved in dopaminergic neurotransmission and has been implicated in a number of neurodegenerative disorders, such as Parkinson's disease. Recent studies, in humans and in rat and monkey models, have suggested that alpha-synuclein may play a role in the development and maintenance of certain addictive disorders. Methods: Fifteen single-nucleotide polymorphisms (SNPs) in the alpha-synuclein gene (SNCA) and 1 upstream microsatellite repeat (NACP-REP1) were assayed in Southwest (SW; n=514) and Plains (n=420) American Indian populations. Patterns of linkage disequilibrium (LD) at SNCA were determined for the 2 populations and compared with Caucasian, African, and Asian populations in the HapMap database (http://www.hapmap.org). Assayed alleles and constructed haplotypes in the study populations were tested for association with 4 clinical phenotypes [alcohol dependence, alcohol use disorders, drug dependence, and drug use disorders (lifetime diagnoses)] as well as with 2 symptom count phenotypes (all 18 questions and the 8 questions diagnostic for alcohol dependence). Results: Patterns of LD at SNCA were similar in both Indian populations and were consistent with the LD structure in other populations as reflected in the HapMap database. Single allele tests revealed significant associations between 4 SNPs and drug dependence in the SW population and between 2 of those SNPs plus 2 other SNPs and drug dependence in SW males only. In the Plains population, a significant association was detected only in males between 2 SNPs and alcohol use disorders and between 1 SNP and alcohol dependence. In the SW population, 1 SNP was marginally significant with the total symptom count. However, in all cases, the support was modest and disappeared with correction for multiple comparisons. No association was found between constructed haplotypes and any of the phenotypes in either population. Conclusions: Despite modest support for association between multiple SNCA SNPs and several of the addictive disorders tested in this study, statistical significance disappeared after correction for multiple testing. Thus, our data do not support a role for a variant in the SNCA gene that contributes to alcohol or drug addiction in the 2 studied American Indian populations. Future research may focus on variants in the promoter region that could cause the changes in mRNA and protein levels observed in previous studies. [ABSTRACT FROM AUTHOR]

Objectives: Maternal stress has long been associated with lower birthweight, which is associated with adverse health outcomes including many adult diseases. The underlying mechanisms remain elusive although changes in gene expression may play a role. Studies are only beginning to test how maternal stress impacts gene expression as reflected in the transcriptome., Materials and Methods: In a cohort of mothers and newborns in the eastern Democratic Republic of Congo (n=93), we studied the effects of four maternal stress measures (chronic stress, war trauma, sexual trauma, and general trauma) on the transcriptomes of maternal venous blood, newborn venous blood, and placental tissues, and on newborn birthweight. Maternal stress was investigated as independent measures, principal components, and clusters identified through machine learning. The transcriptome was assayed using the ClariomD chip. Multiple regression models were used to test for associations between maternal stress measures, the transcriptome, and newborn birthweight., Results: None of the maternal stress measures showed an association with expression of individual genes. In contrast, when testing global gene expression, war trauma was significantly associated with the placental transcriptome. War trauma was also significantly associated with birthweight in multiple models. Mediation analysis indicated that ~14% of the effect of war trauma on birthweight was mediated by a placental gene expression component., Discussion: Our results suggest that gene expression in the placenta, which represents the interface between mother and developing fetus, may partially mediate the negative impact of maternal stress on newborn birthweight.

The GPT-4 large language model (LLM) and ChatGPT chatbot have emerged as accessible and capable tools for generating English-language text in a variety of formats. GPT-4 has previously performed well when applied to questions from multiple standardized examinations. However, further evaluation of trustworthiness and accuracy of GPT-4 responses across various knowledge domains is essential before its use as a reference resource. Here, we assess GPT-4 performance on nine graduate-level examinations in the biomedical sciences (seven blinded), finding that GPT-4 scores exceed the student average in seven of nine cases and exceed all student scores for four exams. GPT-4 performed very well on fill-in-the-blank, short-answer, and essay questions, and correctly answered several questions on figures sourced from published manuscripts. Conversely, GPT-4 performed poorly on questions with figures containing simulated data and those requiring a hand-drawn answer. Two GPT-4 answer-sets were flagged as plagiarism based on answer similarity and some model responses included detailed hallucinations. In addition to assessing GPT-4 performance, we discuss patterns and limitations in GPT-4 capabilities with the goal of informing design of future academic examinations in the chatbot era., (© 2024. The Author(s).)

"Touch DNA" is a form of trace DNA that is presumed to be deposited when an individual touches something and leaves behind DNA-containing skin cells, sweat, or other fluids. While touch DNA is often the result of direct contact (i.e., primary transfer), it can also be indirectly transferred between surfaces or individuals (e.g., secondary or tertiary transfer). Even experts cannot distinguish between different types of transfer and do not fully understand which variables affect direct versus indirect transfer or how often each type of transfer occurs. In this study, we utilize an innovative protocol that combines a paired male and female transfer DNA experimental design with an Amelogenin qPCR assay to generate data on primary, secondary, and tertiary DNA transfer. We report frequencies of indirect DNA transfer and also investigate the potential effects of participant age, self-identified ethnicity, and skin conditions on DNA transfer. Out of 22 experimental trials, we detected primary transfer (male + female) in 71% of trials, secondary DNA transfer in 50% of trials, and tertiary DNA transfer in 27% of trials. No significant associations were found between primary DNA transfer and age, self-identified ancestry, or skin conditions, however, all individuals with sloughing skin conditions demonstrated primary DNA transfer and we suggest this variable be explored in larger samples. These results contribute to a better understanding of the conditions under which secondary and tertiary DNA transfer occurs and can be used to propose realistic DNA transfer scenarios in court cases., (© 2023 American Academy of Forensic Sciences.)

In the present scoping review, we explore whether existing evidence supports the premise that social determinants of health (SDoH) affect immigrant health outcomes through their effects on the microbiome. We adapt the National Institute on Minority Health and Health Disparities' research framework to propose a conceptual model that considers the intersection of SDoH, the microbiome, and health outcomes in immigrants. We use this conceptual model as a lens through which to explore recent research about SDoH, biological factors associated with changes to immigrants' microbiomes, and long-term health outcomes. In the 17 articles reviewed, dietary acculturation, physical activity, ethnicity, birthplace, age at migration and length of time in the host country, socioeconomic status, and social/linguistic acculturation were important determinants of postmigration microbiome-related transformations. These factors are associated with progressive shifts in microbiome profile with time in host country, increasing the risks for cardiometabolic, mental, immune, and inflammatory disorders and antibiotic resistance. The evidence thus supports the premise that SDoH influence immigrants' health postmigration, at least in part, through their effects on the microbiome. Omission of important postmigration social-ecological variables (e.g., stress, racism, social/family relationships, and environment), limited research among minoritized subgroups of immigrants, complexity and inter- and intra-individual differences in the microbiome, and limited interdisciplinary and biosocial collaboration restrict our understanding of this area of study. To identify potential microbiome-based interventions and promote immigrants' well-being, more research is necessary to understand the intersections of immigrant health with factors from the biological, behavioral/psychosocial, physical/built environment, and sociocultural environment domains at all social-ecological levels., (© 2023 Wiley Periodicals LLC.)

Prenatal maternal stress has a negative impact on child health but the mechanisms through which maternal stress affects child health are unclear. Epigenetic variation, such as DNA methylation, is a likely mechanistic candidate as DNA methylation is sensitive to environmental insults and can regulate long-term changes in gene expression. We recruited 155 mother-newborn dyads in the Democratic Republic of Congo to investigate the effects of maternal stress on DNA methylation in mothers and newborns. We used four measures of maternal stress to capture a range of stressful experiences: general trauma, sexual trauma, war trauma, and chronic stress. We identified differentially methylated positions (DMPs) associated with general trauma, sexual trauma, and war trauma in both mothers and newborns. No DMPs were associated with chronic stress. Sexual trauma was positively associated with epigenetic age acceleration across several epigenetic clocks in mothers. General trauma and war trauma were positively associated with newborn epigenetic age acceleration using the extrinsic epigenetic age clock. We tested the top DMPs for enrichment of DNase I hypersensitive sites (DHS) and found no enrichment in mothers. In newborns, top DMPs associated with war trauma were enriched for DHS in embryonic and foetal cell types. Finally, one of the top DMPs associated with war trauma in newborns also predicted birthweight, completing the cycle from maternal stress to DNA methylation to newborn health outcome. Our results indicate that maternal stress is associated with site-specific changes in DNAm and epigenetic age acceleration in both mothers and newborns.

Background: Most research on discrimination and health operationalizes discrimination as direct individual experiences. Here, we examine the social patterning of vicarious discrimination, an important but largely overlooked dimension of discrimination., Methods: Drawing on community-based participatory research with a multi-stage probability sample (n = 178) of African Americans in Tallahassee, Florida, we measured vicarious discrimination, or exposure to discrimination through one's family and friends. We used chi-square tests to examine gender differences in the social domains and relational sources of vicarious discrimination. Negative binomial regression models were fit to identify predictors of exposure to vicarious discrimination., Results: Vicarious discrimination is more prevalent than direct experiences of discrimination (73 versus 61%) and more than 20% of participants report vicarious discrimination in the absence of direct discrimination. For women, vicarious discrimination most often involved the workplace; for men, police. However, gender differences are smaller for vicarious versus direct discrimination. Close friends and children were top relational sources of vicarious discrimination for men and women, respectively. Middle-aged participants reported the most vicarious discrimination., Conclusions: Overall, our data show that vicarious discrimination is more common than widely understood and associated with individual-level sociodemographic characteristics that index one's position in broader social systems. The prevalence of vicarious discrimination in the absence of direct discrimination suggests that standard approaches, which measure individual exposures in isolation, are subject to misclassification bias. Our results imply that existing research on discrimination and health, which already demonstrates substantial harm, underestimates African Americans' true exposures to salient aspects of discrimination., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background and Objectives: The Developmental Origins of Health and Disease hypothesis posits that early life adversity is associated with poor adult health outcomes. Epidemiological evidence has supported this framework by linking low birthweight with adult health and mortality, but the mechanisms remain unclear. Accelerated epigenetic aging may be a pathway to connect early life experiences with adult health outcomes, based on associations of accelerated epigenetic aging with increased morbidity and mortality., Methodology: Sixty-seven mother-infant dyads were recruited in the eastern Democratic Republic of Congo. Birthweight data were collected at birth, and blood samples were collected at birth and follow-up visits up to age 3. DNA methylation data were generated with the Illumina MethylationEPIC array and used to estimate epigenetic age. A multilevel model was used to test for associations between birthweight and epigenetic age acceleration., Results: Chronological age was highly correlated with epigenetic age from birth to age 3 ( r = 0.95, p < 2.2 × 10 -16 ). Variation in epigenetic age acceleration increased over time. Birthweight, dichotomized around 2500 g, predicted epigenetic age acceleration over the first 3 years of life ( b = -0.39, p = 0.005)., Conclusions and Implications: Our longitudinal analysis provides the first evidence for accelerated epigenetic aging that emerges between birth and age 3 and associates with low birthweight. These results suggest that early life experiences, such as low birthweight, may shape the trajectory of epigenetic aging in early childhood. Furthermore, accelerated epigenetic aging may be a pathway that links low birthweight and poor adult health outcomes., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Foundation for Evolution, Medicine, and Public Health.)

Forensic "touch" DNA samples are low-quantity samples that are recovered from surfaces that have been touched by single or multiple individuals. These samples can include DNA from primary contributors who directly touched the surface, as well as secondary contributors whose DNA was transferred to the surface through an intermediary. It is difficult to determine the type of transfer, or how often and under what conditions DNA transfer occurs. In this paper, we present an innovative protocol that combines (1) a paired male and female transfer DNA experimental design in which the presence of male DNA indicates secondary transfer and (2) a cost-effective quantitative PCR (qPCR) assay of a sex-specific region in the Amelogenin gene to detect male and female DNA. We evaluate the ability of the Amelogenin qPCR assay to detect low concentrations of male and female DNA in mixed samples. We also test experimental DNA samples using our transfer DNA protocol to differentiate primary and secondary DNA transfer. Male DNA was detected in the majority of known mixed samples, even in samples with 4× more female DNA-this result demonstrates the ability to detect low concentrations of male DNA and the presence of secondary transfer DNA in our experimental design. Primary DNA transfer was detected in 100% of our experimental trials and secondary DNA transfer was detected in 37.5% of trials. Our innovative protocol mimics realistic case scenarios to establish rates of primary and secondary DNA transfer in an inexpensive and simplified manner., (© 2023 American Academy of Forensic Sciences.)

The developing infant gut microbiome is highly sensitive to environmental exposures, enabling its evolution into an organ that supports the immune system, confers protection from infection, and facilitates optimal gut and central nervous system function. In this study, we focus on the impact of maternal psychosocial stress on the infant gut microbiome. Forty-seven mother-infant dyads were recruited at the HEAL Africa Hospital in Goma, Democratic Republic of Congo. Extensive medical, demographic, and psychosocial stress data were collected at birth, and infant stool samples were collected at six weeks, three months, and six months. A composite maternal psychosocial stress score was created, based on eight questionnaires to capture a diverse range of stress exposures. Full-length 16S rRNA gene sequences were generated. Infants of mothers with high composite stress scores showed lower levels of gut microbiome beta diversity at six weeks and three months, as well as higher levels of alpha diversity at six months compared to infants of low stress mothers. Longitudinal analyses showed that infants of high stress mothers had lower levels of health-promoting Lactobacillus gasseri and Bifidobacterium pseudocatenulatum at six weeks compared to infants of low stress mothers, but the differences largely disappeared by three to six months. Previous research has shown that L. gasseri can be used as a probiotic to reduce inflammation, stress, and fatigue, as well as to improve mental state, while B. pseudocatenulatum is important in modulating the gut-brain axis in early development and in preventing mood disorders. Our finding of reduced levels of these health-promoting bacteria in infants of high stress mothers suggests that the infant gut microbiome may help mediate the effect of maternal stress on infant health and development.

Background: In the United States, hypertension disproportionately afflicts over half of African American adults, many of whom also experience racial discrimination. Understanding gene × discrimination effects may help explain racial disparities in hypertension., Methods: We tested for the main effects and interactive effects of 5 candidate single nucleotide polymorphisms (SNPs: rs2116737, rs11190458, rs2445762, rs2597955, and rs2416545) and experiences of discrimination on blood pressure (BP) in African Americans not taking antihypertensive medications in the Jackson Heart Study from Mississippi (n = 2,933). Multiple linear regression models assumed an additive genetic model and adjusted for ancestry, age, sex, body mass index, education, and relatedness. We additionally tested recessive and dominant genetic models., Results: Discrimination was significantly associated with higher diastolic BP (P = 0.003). In contrast, there were no main effects of any SNP on BP. When analyzing SNPs and discrimination together, SGCD (Sarcoglycan Delta; rs2116737) demonstrated a gene × environment interaction. Specifically, an SGCD × Discrimination interaction was associated with systolic BP (β =1.95, P = 0.00028) in a recessive model. Participants carrying a T allele, regardless of discrimination experiences, and participants with a GG genotype and high experiences of discrimination had higher systolic BP than participants with a GG genotype and low experiences of discrimination. This finding suggests the SGCD GG genotype may have a protective effect on systolic BP, but only in a setting of low discrimination., Conclusions: The inclusion of culturally relevant stressors, like discrimination, may be important to understand the gene-environment interplay likely underlying complex diseases with racial health inequities., (© The Author(s) 2022. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Responses to early life adversity differ greatly across individuals. Elucidating which factors underlie this variation can help us better understand how to improve health trajectories. Here we used a case:control study of refugee and non-refugee youth, differentially exposed to war-related trauma, to investigate the effects of genetics and psychosocial environment on response to trauma. We investigated genetic variants in two genes (serotonin transporter, 5-HTT, and catechol-O-methyltransferase, COMT) that have been implicated in response to trauma. We collected buccal samples and survey data from 417 Syrian refugee and 306 Jordanian non-refugee youth who were enrolled in a randomized controlled trial to evaluate a mental health-focused intervention. Measures of lifetime trauma exposure, resilience, and six mental health and psychosocial stress outcomes were collected at three time points: baseline, ~13 weeks, and ~48 weeks. We used multilevel models to identify gene x environment (GxE) interactions and direct effects of the genetic variants in association with the six outcome measures over time. We did not identify any interactions with trauma exposure, but we did identify GxE interactions with both genes and resilience; 1) individuals with high expression (HE) variants of 5-HTTLPR and high levels of resilience had the lowest levels of perceived stress and 2) individuals homozygous for the Val variant of COMT with high levels of resilience showed stable levels of post-traumatic stress symptoms. We also identified a direct protective effect of 5-HTTLPR HE homozygotes on perceived insecurity. Our results point to novel interactions between the protective effects of genetic variants and resilience, lending support to ideas of differential susceptibility and altered stress reactivity in a cohort of war-affected adolescents., Competing Interests: The authors have declared that no competing interests exist.

Bioengineered platforms, intended to be used in the investigation of human health and disease, often incorporate cells of unknown ancestry or that lack diversity. To develop tools and platforms that benefit the entire human population, we must consider the ancestry of cells and intentionally diversify the cells we use in our designs., Competing Interests: Competing interests The authors declare no competing interests.

Objectives: The World Health Organization estimates that almost 300 million people suffer from depression worldwide. African Americans are understudied for depression-related phenotypes despite widespread racial disparities. In our study of African Americans, we integrated information on psychosocial stressors with genetic variation in order to better understand how these factors associated with depressive symptoms., Methods: Our research strategy combined information on financial strain and social networks with genetic data to investigate variation in symptoms of depression (CES-D scores). We collected self-report data on depressive symptoms, financial strain (difficulty paying bills) and personal social networks (a model of an individual's social environment), and we genotyped genetic variants in five genes previously implicated in depressive disorders (HTR1a, BDNF, GNB3, SLC6A4, and FKBP5) in 128 African Americans residing in Tallahassee, Florida. We tested for direct and gene-environment interactive effects of the psychosocial stressors and genetic variants on depressive symptoms., Results: Significant associations were identified between high CES-D scores and a stressful social environment (i.e., a high percentage of people in participants' social network who were a source of stress) and high financial strain. Only one genetic variant (rs1360780 in FKBP5) was significantly associated with CES-D scores and only when psychosocial stressors were included in the model; the T allele had an additive effect on depressive symptoms. Sex was also significantly associated with CES-D score in the model with psychosocial stressors and genetic variants; males had higher CES-D scores. No significant interactive effects were detected., Conclusions: A stressful social environment and material disadvantage increase depressive symptoms in the study population. Additional associations with FKBP5 and male sex were revealed in models that included both psychosocial and genetic data. Our results suggest that incorporating psychosocial stressors may empower future genetic association studies and help clarify the biological consequences of social and financial stress., (© 2021 Wiley Periodicals LLC.)

Special Issue - Race reconciled II: Interpreting and communicating biological variation and race in 2021 Many sociocultural factors, like poverty and trauma, or homelessness versus a safe neighborhood, can get "under our skin" and affect our lives. These factors may also get "into our genes" through epigenetic changes that influence how genes are expressed. Changes in gene expression can further influence how we respond to sociocultural factors and how those factors impact our physical and mental health, creating a feedback loop between our sociocultural environment and our genome., (© 2021 Wiley Periodicals LLC.)

Enhanced production of dehydroepiandrosterone (DHEA) by the foetal hypothalamic-pituitary-adrenal (HPA) axis enables maturational events critical for labour induction and neonatal adaptation. Despite knowledge of the interconnected nature of maternal and foetal physiology and dramatic changes in DHEA production after birth, few studies have examined DHEA levels in newborns and none have examined DHEA's response to acute stress. Understanding normative patterns of early DHEA activity is needed to accurately assess functioning of the biological stress system with relevance for health and development. The present study analysed DHEA concentrations and change after stress among 93 newborns and associations with pregnancy, delivery and demographic risk factors. Three saliva samples, collected prior to and following a blood draw stressor, were used to determine baseline and stress reactive DHEA levels. Mothers self-reported on health behaviours during pregnancy. Data on obstetric factors were obtained from medical records. DHEA levels declined from pre- to post-stressor assessments. Results also showed that post-stressor DHEA change was significantly associated with administration of medications used to treat pain and accelerate labour. However, there was no significant variation in DHEA pre-stress levels or change after stress as a function of time after birth. By capturing DHEA levels after birth, the present study provides a window into prenatal health of the HPA system. The study also advances knowledge of DHEA in newborns by providing data on reference levels and important covariates. This information on basic adrenal physiology provides a foundation that can be expanded on to enhance understanding of early hypothalamic-pituitary-adrenal axis activity., (© 2020 British Society for Neuroendocrinology.)

Objectives: Experiences of interpersonal discrimination are pervasive stressors in the lives of African Americans. Increased discrimination stress may cause premature aging. Telomere length (TL) is a plastic genetic trait that is an emerging indicator of cellular health and aging. Short TL is a risk factor for the earlier onset of disease. TL shortens with age, a process that may be accelerated by psychosocial stress. Our study explores the relationship between TL and experiences of discrimination in the form of self-reported unfair treatment (UT)., Methods: Using a qPCR-based method, we measured TL in DNA from saliva samples provided by 135 African American adults from Tallahassee, FL. We developed discrimination measures using a modified survey that explores nine social domains of self-reported unfair treatment experienced both directly and indirectly. We used multiple regression to examine associations between UT and TL., Results: We found that racial discrimination in the form of self-reported unfair treatment attributed to race (UT-Race-Self) is inversely associated with TL., Conclusions: The significant association between increased UT-Race-Self and shorter telomeres supports the hypothesis that psychosocial stress stemming from racial discrimination may affect TL. The potential impact of discrimination on TL may contribute to premature biological aging and racial health inequalities seen in African Americans., (© 2019 Wiley Periodicals, Inc.)

Early childhood trauma can have profound and lifelong effects on adult mental health and psychosocial wellbeing. Nevertheless, responses to trauma are highly variable. Genetic variants may help explain variation in responses to trauma by identifying alleles that associate with changes in mental health measures. Protective factors, such as resilience, likely also play an important role in responses to trauma. The effects of genetic variants, in combination with protective factors, on psychosocial health are not well understood, particularly in non-Western contexts. In this study, we test the relative influence of genetic variants of monoamine oxidase A (MAOA, a gene proposed to influence the impact of childhood trauma on adult violence and antisocial behavior), levels of resilience, and exposure to traumatic events on psychosocial stress and mental health trajectories over time. We use data from a cohort of 12-18-year-old Syrian refugees who were forcibly displaced to neighboring Jordan (n = 399). DNA samples and survey data on trauma exposure, resilience (CYRM-12), and psychosocial stress were collected at three time points: baseline, ~13 weeks, and ~48 weeks. Using multilevel models, we identified an association of MAOA variant, in males only, with symptom scores of psychosocial stress on the Perceived Stress Scale (PSS) over time (p = 8.1 x 10-4). We also found that resilience is strongly associated with PSS (p = 7.9 x 10-9), underscoring the importance of protective factors in influencing levels of psychosocial stress. Furthermore, there was an additive effect wherein the sharpest reductions in perceived psychosocial stress are seen in low-activity MAOA males with low trauma exposure or high resilience levels. Our results highlight the value of studies that integrate genetic and psychosocial factors to better understand complex phenotypes, such as responses to trauma in contexts of high trauma exposure., Competing Interests: The authors have declared that no competing interests exist.

Objectives: Modern humans are thought to have interbred with Neanderthals in the Near East soon after modern humans dispersed out of Africa. This introgression event likely took place in either the Levant or southern Arabia depending on the dispersal route out of Africa that was followed. In this study, we compare Neanderthal introgression in contemporary Levantine and southern Arabian populations to investigate Neanderthal introgression and to study Near Eastern population history., Materials and Methods: We analyzed genotyping data on >400,000 autosomal SNPs from seven Levantine and five southern Arabian populations and compared these data to those from populations from around the world including Neanderthal and Denisovan genomes. We used f 4 and D statistics to estimate and compare levels of Neanderthal introgression between Levantine, southern Arabian, and comparative global populations. We also identified 1,581 putative Neanderthal-introgressed SNPs within our dataset and analyzed their allele frequencies as a means to compare introgression patterns in Levantine and southern Arabian genomes., Results: We find that Levantine and southern Arabian populations have similar levels of Neanderthal introgression to each other but lower levels than other non-Africans. Furthermore, we find that introgressed SNPs have very similar allele frequencies in the Levant and southern Arabia, which indicates that Neanderthal introgression is similarly distributed in Levantine and southern Arabian genomes., Discussion: We infer that the ancestors of contemporary Levantine and southern Arabian populations received Neanderthal introgression prior to separating from each other and that there has been extensive gene flow between these populations., (© 2019 Wiley Periodicals, Inc.)

Stress is known to affect health throughout life and into future generations, but the underlying molecular mechanisms are unknown. We tested the hypothesis that maternal psychosocial stress influences DNA methylation (DNAm), which in turn impacts newborn health outcomes. Specifically, we analyzed DNAm at individual, regional, and genome-wide levels to test for associations with maternal stress and newborn birth weight. Maternal venous blood and newborn cord blood ( n = 24 and 22, respectively) were assayed for methylation at ∼450,000 CpG sites. Methylation was analyzed by examining CpG sites individually in an epigenome-wide association study (EWAS), as regional groups using variably methylated region (VMR) analysis in maternal blood only, and through the epigenome-wide measures using genome-wide mean methylation (GMM), Horvath's epigenetic clock, and mitotic age. These methylation measures were tested for association with three measures of maternal stress (maternal war trauma, chronic stress, and experience of sexual violence) and one health outcome (newborn birth weight). We observed that maternal experiences of war trauma, chronic stress, and sexual assault were each associated with decreased newborn birth weight ( p < 1.95 × 10 -7 in all cases). Testing individual CpG sites using EWAS, we observed no associations between DNAm and any measure of maternal stress or newborn birth weight in either maternal or cord blood, after Bonferroni multiple testing correction. However, the top-ranked CpG site in maternal blood that associated with maternal chronic stress and sexual violence before multiple testing correction is located near the SPON1 gene. Testing at a regional level, we found increased methylation of a VMR in maternal blood near SPON1 that was associated with chronic stress and sexual violence after Bonferroni multiple testing correction ( p = 1.95 × 10 -7 and 8.3 × 10 -6 , respectively). At the epigenomic level, cord blood GMM was associated with significantly higher levels of war trauma ( p = 0.025) and was suggestively associated with sexual violence ( p = 0.053). The other two epigenome-wide measures were not associated with maternal stress or newborn birth weight in either tissue type. Despite our small sample size, we identified associations even after conservative multiple testing correction. Specifically, we found associations between DNAm and the three measures of maternal stress across both tissues; specifically, a VMR in maternal blood and GMM in cord blood were both associated with different measures of maternal stress. The association of cord blood GMM, but not maternal blood GMM, with maternal stress may suggest different responses to stress in mother and newborn. It is noteworthy that we found associations only when CpG sites were analyzed in aggregate, either as VMRs or as a broad summary measure of GMM.

The Austronesian dispersal across the Indonesian Ocean to Madagascar and the Comoros has been well documented, but in an unexplained anomaly, few to no traces have been found of the Austronesian expansion in East Africa or the Arabian Peninsula. To revisit this peculiarity, we surveyed the Western Indian Ocean rim populations to identify potential Austronesian genetic ancestry. We generated full mitochondrial DNA genomes and genome-wide genotyping data for these individuals and compared them with the Banjar, the Indonesian source population of the westward Austronesian dispersal. We find strong support for Asian genetic contributions to maternal lineages and autosomal variation in modern day Somalia and Yemen. Surprisingly, this input reveals two apparently different geographic origins and timings of admixture for the Austronesian contact; one at a very early phase (likely associated with the early Austronesian dispersals), and a later movement dating to the end of nineteenth century. These Austronesian gene flows come, respectively, from Madagascar and directly from an unidentified location in Island Southeast Asia. This result reveals a far more complex dynamic of Austronesian dispersals through the Western Indian Ocean than has previously been understood and suggests that Austronesian movements within the Indian Ocean may have been part of a lengthy process, probably continuing well into the modern era., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.)

Epigenetic variation represents a unique aspect of human biological variation that can shed light on our evolutionary history as well as the etiology of human disease. DNA methylation is the most commonly studied type of epigenetic modification and can alter gene expression without changing the underlying DNA sequence. DNA methylation occurs throughout all living organisms although its function seems to have evolved from genome defense in fungi, bacteria and plants to a more complex role in gene regulation and cellular differentiation in animals. Human DNA methylation was originally studied in imprinting diseases and cancer, but more recently has been investigated as a mechanism to mediate the impact of environmental and psychosocial stressors on human health and disease., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Deaths due to hypertension in the US are highest among African Americans, who have a higher prevalence of hypertension and more severe hypertensive symptoms. Research indicates that there are both genetic and sociocultural risk factors for hypertension. Racial disparities in hypertension also likely involve genetic and sociocultural factors, but the factors may interact and manifest differently across racial groups. Here we use a biocultural approach to integrate genetic and social network data to better understand variation in blood pressure. We assay genetic variation at the angiotensin I converting enzyme gene (ACE) and analyze social network composition and structure in African Americans living in Tallahassee, FL (n = 138). We demonstrate that models including both genetic and social network data explain significantly more variation in blood pressure and have better model diagnostics than do models including only one datatype. Specifically, optimal models for systolic and diastolic blood pressure explain a notable 35% and 21%, respectively, of blood pressure variation. Analysis of the social networks reveals that individuals whose networks are dominated by family connections and are more fragmented have higher blood pressure. Historically, family support has been associated with better mental and physical health, but our results suggest that those family connections can also take a toll on health. These findings raise compelling questions regarding the roles of genetics, family, and social environment in hypertension in the African American community and suggest that interactions among these factors may help explain racial disparities in hypertension more accurately than any of the factors alone., Competing Interests: The authors have declared that no competing interests exist.

Maternal stress has been linked to low birth weight in newborns. One potential pathway involves epigenetic changes at candidate genes that may mediate the effects of prenatal maternal stress on birth weight. This relationship has been documented in stress-related genes, such as NR3C1. There is less literature exploring the effect of stress on growth-related genes. IGF1 and IGF2 have been implicated in fetal growth and development, though via different mechanisms as IGF2 is under imprinting control. In this study, we tested for associations between prenatal stress, methylation of IGF1 and IGF2, and birth weight. A total of 24 mother-newborn dyads in the Democratic Republic of Congo were enrolled. Ethnographic interviews were conducted with mothers at delivery to gather culturally relevant war-related and chronic stressors. DNA methylation data were generated from maternal venous, cord blood and placental tissue samples. Multivariate regressions were used to test for associations between stress measures, DNA methylation and birth weight in each of the three tissue types. We found an association between IGF2 methylation in maternal blood and birth weight. Previous literature on the relationship between IGF2 methylation and birth weight has focused on methylation at known differentially methylated regions in cord blood or placental samples. Our findings indicate there may be links between the maternal epigenome and low birth weight that rely on mechanisms outside known imprinting pathways. It thus may be important to consider the effect of maternal exposures and epigenetic profiles on birth weight even in the setting of maternally imprinted genes such as IGF2.

Objectives: Early life stress is known to have enduring biological effects, particularly with respect to health. Epigenetic modifications, such as DNA methylation, are a possible mechanism to mediate the biological effect of stress. We previously found correlations between maternal stress, newborn birthweight, and genome-wide measures of DNA methylation. Here we investigate ten genes related to the methylation/demethylation complex in order to better understand the impact of stress on health., Materials and Methods: DNA methylation and genetic variants at methylation/demethylation genes were assayed. Mean methylation measures were constructed for each gene and tested, in addition to genetic variants, for association with maternal stress measures based on interview and survey data (chronic stress and war trauma), maternal venous, and newborn cord genome-wide mean methylation (GMM), and birthweight., Results: After cell type correction, we found multiple pairwise associations between war trauma, maternal GMM, maternal methylation at DNMT1, DNMT3A, TET3, and MBD2, and birthweight., Conclusions: The association of maternal GMM and maternal methylation at DNMT1, DNMT3A, TET3, and MBD2 is consistent with the role of these genes in establishing, maintaining and altering genome-wide methylation patterns, in some cases in response to stress. DNMT1 produces one of the primary enzymes that reproduces methylation patterns during DNA replication. DNMT3A and TET3 have been implicated in genome-wide hypomethylation in response to glucocorticoid hormones. Although we cannot determine the directionality of the genic and genome-wide changes in methylation, our results suggest that altered methylation of specific methylation genes may be part of the molecular mechanism underlying the human biological response to stress., (© 2017 Wiley Periodicals, Inc.)

Objectives: The Northern Dispersal Route (NDR) and Southern Dispersal Route (SDR) are hypothesized to have been used by modern humans in the dispersal out of Africa. The NDR follows the Nile into Northeast Africa and crosses the Red Sea into the Levant. The SDR emerges from the Horn of Africa and crosses the Bab el-Mandeb into southern Arabia. In this study, we analyze genetic data from populations living along the NDR and SDR to test support for each dispersal route., Materials and Methods: We genotyped 90 Yemeni samples on the Affymetrix Human Origins array. We analyzed these data with published data from Levantine and other southern Arabian populations as well as 157 comparative populations for a total sample size of >550,000 genetic variants from >2,000 individuals in >160 populations. We calculated outgroup f 3 statistics to test how Levantine and southern Arabian populations relate to African populations living along the NDR and SDR and to other non-African populations., Results: We find that Levantine and southern Arabian populations bear similar genetic relationships to both African and non-African populations, thus providing no support for the use of one dispersal route over the other., Discussion: Our results are consistent with a history of gene flow between the Levant and southern Arabia. Consideration of genetic, archaeological, and paleoclimate data provide a slight edge for the SDR but, ultimately, more data are needed to definitively identify which dispersal route out of Africa was used., (© 2017 Wiley Periodicals, Inc.)

Background: The BDNF gene codes for brain-derived neurotrophic factor, a growth factor involved in neural development, cell differentiation, and synaptic plasticity. Present in both the brain and periphery, BDNF plays critical roles throughout the body and is essential for placental and fetal development. Rodent studies show that early life stress, including prenatal stress, broadly alters BDNF methylation, with presumed changes in gene expression. No studies have assessed prenatal exposure to maternal traumatic stress and BDNF methylation in humans. This study examined associations of prenatal exposure to maternal stress and BDNF methylation at CpG sites across the BDNF gene., Results: Among 24 mothers and newborns in the eastern Democratic Republic of Congo, a region with extreme conflict and violence to women, maternal experiences of war trauma and chronic stress were associated with BDNF methylation in umbilical cord blood, placental tissue, and maternal venous blood. Associations of maternal stress and BDNF methylation showed high tissue specificity. The majority of significant associations were observed in putative transcription factor binding regions., Conclusions: This is the first study in humans to examine BDNF methylation in relation to prenatal exposure to maternal stress in three tissues simultaneously and the first in any mammalian species to report associations of prenatal stress and BDNF methylation in placental tissue. The findings add to the growing body of evidence highlighting the importance of considering epigenetic effects when examining the impacts of trauma and stress, not only for adults but also for offspring exposed via effects transmitted before birth.

Spinocerebellar ataxia type 10 (SCA10), an autosomal dominant cerebellar ataxia disorder, is caused by a non-coding ATTCT microsatellite repeat expansion in the ataxin 10 gene. In a subset of SCA10 families, the 5'-end of the repeat expansion contains a complex sequence of penta- and heptanucleotide interruption motifs which is followed by a pure tract of tandem ATCCT repeats of unknown length at its 3'-end. Intriguingly, expansions that carry these interruption motifs correlate with an epileptic seizure phenotype and are unstable despite the theory that interruptions are expected to stabilize expanded repeats. To examine the apparent contradiction of unstable, interruption-positive SCA10 expansion alleles and to determine whether the instability originates outside of the interrupted region, we sequenced approximately 1 kb of the 5'-end of SCA10 expansions using the ATCCT-PCR product in individuals across multiple generations from four SCA10 families. We found that the greatest instability within this region occurred in paternal transmissions of the allele in stretches of pure ATTCT motifs while the intervening interrupted sequences were stable. Overall, the ATCCT interruption changes by only one to three repeat units and therefore cannot account for the instability across the length of the disease allele. We conclude that the AT-rich interruptions locally stabilize the SCA10 expansion at the 5'-end but do not completely abolish instability across the entire span of the expansion. In addition, analysis of the interruption alleles across these families support a parsimonious single origin of the mutation with a shared distant ancestor.

The current model for peopling of the Americas involves divergence from an ancestral Asian population followed by a period of population isolation and genetic diversification in Beringia, and finally, a rapid expansion into and throughout the Americas. Studies in the 1970s sought to characterize the biological relationships between different indigenous populations and first proposed an occupation of Beringia. More recent studies using molecular genetic markers often neglect to reference early works that laid the groundwork for current colonization models. We address this matter, and briefly summarize the literature and technological advances that contributed to our current understanding of the peopling of the Americas. Furthermore, we argue that describing the process of peopling of the Americas as "migrations from Asia" minimizes the significant genetic diversification that occurred outside of Asia, and offends indigenous Americans by discounting their origin narratives and land rights. Rather than referring to the indigenous peoples of the Americas as "migrants" or "immigrants," we recommend consistency in the language used to describe all post-glacial expansions of people into Asia, Europe and the Americas., (© 2017 Wiley Periodicals, Inc.)

Sequencing of the human genome and decades of genetic association and linkage studies have dramatically improved our understanding of the etiology of many diseases. However, the multiple causes of complex diseases are still not well understood, in part because genetic and sociocultural risk factors are not typically investigated concurrently. Hypertension is a leading risk factor for cardiovascular disease and afflicts more African Americans than any other racially defined group in the US. Few genetic loci for hypertension have been replicated across populations, which may reflect population-specific differences in genetic variants and/or inattention to relevant sociocultural factors. Discrimination is a salient sociocultural risk factor for poor health and has been associated with hypertension. Here we use a biocultural approach to study blood pressure (BP) variation in African Americans living in Tallahassee, Florida by genotyping over 30,000 single nucleotide polymorphisms (SNPs) and capturing experiences of discrimination using novel measures of unfair treatment of self and others (n = 157). We perform a joint admixture and genetic association analysis for BP that prioritizes regions of the genome with African ancestry. We only report significant SNPs that were confirmed through our simulation analyses, which were performed to determine the false positive rate. We identify eight significant SNPs in five genes that were previously associated with cardiovascular diseases. When we include measures of unfair treatment and test for interactions between SNPs and unfair treatment, we identify a new class of genes involved in multiple phenotypes including psychosocial distress and mood disorders. Our results suggest that inclusion of culturally relevant stress measures, like unfair treatment in African Americans, may reveal new genes and biological pathways relevant to the etiology of hypertension, and may also improve our understanding of the complexity of gene-environment interactions that underlie complex diseases., Competing Interests: The authors have declared that no competing interests exist.

Objectives: Genetic and archaeological research supports the theory that Arabia was the first region traversed by modern humans as they left Africa and dispersed throughout Eurasia. However, the role of Arabia from the initial migration out of Africa until more recent times is still unclear., Materials and Methods: We have generated 379 new hypervariable segment 1 (HVS-1) sequences from a range of geographic locations throughout Yemen. We compare these data to published HVS-1 sequences representing Arabia and neighboring regions to build a unique dataset of 186 populations and 14,290 sequences., Results: We identify 4,563 haplotypes unevenly distributed across Arabia and neighboring regions. Arabia contains higher proportions of shared haplotypes than the regions with which it shares these haplotypes, suggesting high levels of migration through the region. Populations in Arabia show higher levels of population expansion than those in East Africa, but lower levels than the Near East, Middle East or India. Arabian populations also show very high levels of genetic variation that overlaps with variation from most other regions., Conclusion: We take a population genetics approach to provide a comprehensive view of the relationships of Arabian and neighboring populations. We show that Arabian populations share closest links to the Near East and North Africa, but have a more ancient origin with slower demographic growth and/or lower migration rates. Our conclusions are supported by phylogenetic studies but also suggest that recent migrations have erased signals of earlier events., (© 2015 Wiley Periodicals, Inc.)

Objectives: Anatomically, modern humans are thought to have migrated out of Africa ∼60,000 years ago in the first successful global dispersal. This initial migration may have passed through Yemen, a region that has experienced multiple migrations events with Africa and Eurasia throughout human history. We use Bayesian phylogenetics to determine how ancient and recent migrations have shaped Yemeni mitogenomic variation., Materials and Methods: We sequenced 113 mitogenomes from multiple Yemeni regions with a focus on haplogroups M, N, and L3(xM,N) as these groups have the oldest evolutionary history outside of Africa. We performed Bayesian evolutionary analyses to generate time-measured phylogenies calibrated by Neanderthal and Denisovan mitogenomes in order to determine the age of Yemeni-specific clades., Results: As defined by Yemeni monophyly, Yemeni in situ evolution is limited to the Holocene or latest Pleistocene (ages of clades in subhaplogroups L3b1a1a, L3h2, L3x1, M1a1f, M1a5, N1a1a3, and N1a3 range from 2 to 14 kya) and is often situated within broader Horn of Africa/southern Arabia in situ evolution (L3h2, L3x1, M1a1f, M1a5, and N1a1a3 ages range from 7 to 29 kya). Five subhaplogroups show no monophyly and are candidates for Holocene migration into Yemen (L0a2a2a, L3d1a1a, L3i2, M1a1b, and N1b1a)., Discussion: Yemeni mitogenomes are largely the product of Holocene migration, and subsequent in situ evolution, from Africa and western Eurasia. However, we hypothesize that recent population movements may obscure the genetic signature of more ancient migrations. Additional research, e.g., analyses of Yemeni nuclear genetic data, is needed to better reconstruct the complex population and migration histories associated with Out of Africa., (© 2015 Wiley Periodicals, Inc.)

Exposure to stress early in life permanently shapes activity of the hypothalamic-pituitary-adrenocortical (HPA) axis and the brain. Prenatally, glucocorticoids pass through the placenta to the fetus with postnatal impacts on brain development, birth weight (BW), and HPA axis functioning. Little is known about the biological mechanisms by which prenatal stress affects postnatal functioning. This study addresses this gap by examining the effect of chronic stress and traumatic war-related stress on epigenetic changes in four key genes regulating the HPA axis in neonatal cord blood, placenta, and maternal blood: CRH, CRHBP, NR3C1, and FKBP5. Participants were 24 mother-newborn dyads in the conflict-ridden region of the eastern Democratic Republic of Congo. BW data were collected at delivery and maternal interviews were conducted to assess culturally relevant chronic and war-related stressors. Chronic stress and war trauma had widespread effects on HPA axis gene methylation, with significant effects observed at transcription factor binding (TFB) sites in all target genes tested. Some changes in methylation were unique to chronic or war stress, whereas others were observed across both stressor types. Moreover, stress exposures impacted maternal and fetal tissues differently, supporting theoretical models that stress impacts vary according to life phase. Methylation in several NR3C1 and CRH CpG sites, all located at TFB sites, was associated with BW. These findings suggest that prenatal stress exposure impacts development via epigenetic changes in HPA axis genes., (© 2016 The Authors. Child Development © 2016 Society for Research in Child Development, Inc.)

Hispaniola, comprising Haiti and the Dominican Republic, has been identified as a candidate for malaria elimination. However, incomplete surveillance data in Haiti hamper efforts to assess the impact of ongoing malaria control interventions. Characteristics of the genetic diversity of Plasmodium falciparum populations can be used to assess parasite transmission, which is information vital to evaluating malaria elimination efforts. Here we characterize the genetic diversity of P. falciparum samples collected from patients at seven sites in Haiti using 12 microsatellite markers previously employed in population genetic analyses of global P. falciparum populations. We measured multiplicity of infections, level of genetic diversity, degree of population geographic substructure, and linkage disequilibrium (defined as non-random association of alleles from different loci). For low transmission populations like Haiti, we expect to see few multiple infections, low levels of genetic diversity, high degree of population structure, and high linkage disequilibrium. In Haiti, we found low levels of multiple infections (12.9%), moderate to high levels of genetic diversity (mean number of alleles per locus = 4.9, heterozygosity = 0.61), low levels of population structure (highest pairwise Fst = 0.09 and no clustering in principal components analysis), and moderate linkage disequilibrium (ISA = 0.05, P<0.0001). In addition, population bottleneck analysis revealed no evidence for a reduction in the P. falciparum population size in Haiti. We conclude that the high level of genetic diversity and lack of evidence for a population bottleneck may suggest that Haiti's P. falciparum population has been stable and discuss the implications of our results for understanding the impact of malaria control interventions. We also discuss the relevance of parasite population history and other host and vector factors when assessing transmission intensity from genetic diversity data.

Spinocerebellar ataxia type 10 (SCA10; OMIM #603516) is an autosomal dominant cerebellar ataxia with variably associated extracerebellar signs.(1,2) SCA10 is caused by an expanded noncoding pentanucleotide repeat in ATXN10, which normally ranges from 9 to 32 repeats(3,4); pathogenic alleles have as many as 4,500 repeats.(4) To date, SCA10 has been found exclusively on American continents. In this report, we describe a Chinese Han family with autosomal dominant cerebellar ataxia caused by an SCA10 expansion.

African Americans are 40% more likely to be afflicted with hypertension than are non-Hispanic, white Americans, resulting in a 30% higher instance of mortality due to cardiovascular disease. There is debate about the relative contributions of genetic and sociocultural risk factors to the racial disparity in hypertension. We assayed three Alu insertion polymorphisms located in the ACE (angiotensin 1 converting enzyme), PLAT (plasminogen activator, tissue), and WNK1 (lysine deficient protein kinase 1) genes. We also estimated West African genetic ancestry and developed novel measures of perceived discrimination to create a biocultural model of blood pressure among African American adults in Tallahassee, Florida (n = 158). When tested separately, the ACE Alu noninsertion allele was significantly associated with higher systolic and diastolic blood pressure. In multiple regression analyses, West African genetic ancestry was not associated with blood pressure and reduced the strength of all blood pressure models tested. A gene × environment interaction was identified between the ACE Alu genotype and a new measure of unfair treatment that includes experiences by individuals close to the study participant. Inclusion of the WNK1 Alu genotype further improved this model of blood pressure variation. Our results suggest an association of the ACE and WNK1 genotypes with blood pressure that is consistent with their proposed gene functions. Measures of perceived unfair treatment of others show a threshold effect, with increased blood pressure occurring at higher values. The interaction between the ACE genotype and unfair treatment highlights the benefits of including both genetic and cultural data to investigate complex disease.

Antimalarial drugs are a key tool in malaria elimination programs. With the emergence of artemisinin resistance in southeast Asia, an effort to identify molecular markers for surveillance of resistant malaria parasites is underway. Non-synonymous mutations in the kelch propeller domain (K13-propeller) in Plasmodium falciparum have been associated with artemisinin resistance in samples from southeast Asia, but additional studies are needed to characterize this locus in other P. falciparum populations with different levels of artemisinin use. Here, we sequenced the K13-propeller locus in 82 samples from Haiti, where limited government oversight of non-governmental organizations may have resulted in low-level use of artemisinin-based combination therapies. We detected a single-nucleotide polymorphism (SNP) at nucleotide 1,359 in a single isolate. Our results contribute to our understanding of the global genomic diversity of the K13-propeller locus in P. falciparum populations., (© The American Society of Tropical Medicine and Hygiene.)

The impact of stress on human health is a topic of wide-spread relevance and one that is particularly amenable to multidisciplinary investigation. Stress impacts both our psychological and physical health and, thus, may leave evidence on our psyche, our physical body and our genome. We are interested in the effect of extreme stressors, such as war, on health from the perspective of long-term and multigenerational effects. We integrate sociocultural, biological, and epigenetic data from the war-torn Democratic Republic of Congo (DRC). Between May and August, 2010, we measured sociocultural stress exposure among 25 mother-newborn dyads and we measured health outcomes in newborns. We also collected maternal venous blood, placental tissue, and umbilical cord blood to assay for methylation changes to test for a possible epigenetic mechanism that mediates the effects of stress on health. We provide a qualitative description of the wide range of stress exposures experienced by mothers in our study. As we have shown previously, maternal war stress is strongly associated with newborn birthweight and changes in newborn methylation at the glucocorticoid receptor NR3C1. New results presented here demonstrate that maternal war stress and birthweight are also associated with genome-wide changes in maternal methylation levels. In sum, these results suggest that stress may influence gene expression across a broad spectrum in the individual who directly experiences the stress, i.e., the mother, whereas potential heritable effects in the newborn may be focused on specific genes that are uniquely sensitive to environmental cues., (Copyright © 2014 Wiley Periodicals, Inc.)

Sickle cell disease is a growing global health concern because infants born with the disorder in developing countries are now surviving longer with little access to diagnostic and management options. In Haiti, the current state of sickle cell disease/trait in the population is unclear. To inform future screening efforts in Haiti, we assayed sickle hemoglobin mutations using traditional hemoglobin solubility tests (HST) and add-on techniques, which incorporated spectrophotometry and insoluble hemoglobin separation. We also generated genotype data as a metric for HST performance. We found 19 of 202 individuals screened with HST were positive for sickle hemoglobin, five of whom did not carry the HbS allele. We show that spectrophotometry and insoluble hemoglobin separation add-on techniques could resolve false positives associated with the traditional HST approach, with some limitations. We also discuss the incorporation of insoluble hemoglobin separation observation with HST in suboptimal screening settings like Haiti., (© The American Society of Tropical Medicine and Hygiene.)

Haiti is one of two remaining malaria-endemic countries in the Caribbean. To decrease malaria transmission in Haiti, primaquine was recently added to the malaria treatment public health policy. One limitation of primaquine is that, at certain doses, primaquine can cause hemolytic anemia in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency (G6PDd). In this study, we genotyped two mutations (A376G and G202A), which confer the most common G6PDd variant in West African populations, G6PDd A-. We estimated the frequency of G6PDd A- in a sample of febrile patients enrolled in an on-going malaria study who represent a potential target population for a primaquine mass drug administration. We found that 33 of 168 individuals carried the G6PDd A- allele (includes A- hemizygous males, A- homozygous or heterozygous females) and could experience toxicity if treated with primaquine. These data inform discussions on safe and effective primaquine dosing and future malaria elimination strategies for Haiti., (© The American Society of Tropical Medicine and Hygiene.)

Genetic studies have identified substantial non-African admixture in the Horn of Africa (HOA). In the most recent genomic studies, this non-African ancestry has been attributed to admixture with Middle Eastern populations during the last few thousand years. However, mitochondrial and Y chromosome data are suggestive of earlier episodes of admixture. To investigate this further, we generated new genome-wide SNP data for a Yemeni population sample and merged these new data with published genome-wide genetic data from the HOA and a broad selection of surrounding populations. We used multidimensional scaling and ADMIXTURE methods in an exploratory data analysis to develop hypotheses on admixture and population structure in HOA populations. These analyses suggested that there might be distinct, differentiated African and non-African ancestries in the HOA. After partitioning the SNP data into African and non-African origin chromosome segments, we found support for a distinct African (Ethiopic) ancestry and a distinct non-African (Ethio-Somali) ancestry in HOA populations. The African Ethiopic ancestry is tightly restricted to HOA populations and likely represents an autochthonous HOA population. The non-African ancestry in the HOA, which is primarily attributed to a novel Ethio-Somali inferred ancestry component, is significantly differentiated from all neighboring non-African ancestries in North Africa, the Levant, and Arabia. The Ethio-Somali ancestry is found in all admixed HOA ethnic groups, shows little inter-individual variance within these ethnic groups, is estimated to have diverged from all other non-African ancestries by at least 23 ka, and does not carry the unique Arabian lactase persistence allele that arose about 4 ka. Taking into account published mitochondrial, Y chromosome, paleoclimate, and archaeological data, we find that the time of the Ethio-Somali back-to-Africa migration is most likely pre-agricultural.

Population migration has played an important role in human evolutionary history and in the patterning of human genetic variation. A deeper and empirically-based understanding of human migration dynamics is needed in order to interpret genetic and archaeological evidence and to accurately reconstruct the prehistoric processes that comprise human evolutionary history. Current empirical estimates of migration include either short time frames (i.e. within one generation) or partial knowledge about migration, such as proportion of migrants or distance of migration. An analysis of migration that includes both proportion of migrants and distance, and direction over multiple generations would better inform prehistoric reconstructions. To evaluate human migration, we use GPS coordinates from the place of residence of the Yemeni individuals sampled in our study, their birthplaces and their parents' and grandparents' birthplaces to calculate the proportion of migrants, as well as the distance and direction of migration events between each generation. We test for differences in these values between the generations and identify factors that influence the probability of migration. Our results show that the proportion and distance of migration between females and males is similar within generations. In contrast, the proportion and distance of migration is significantly lower in the grandparents' generation, most likely reflecting the decreasing effect of technology. Based on our results, we calculate the proportion of migration events (0.102) and mean and median distances of migration (96 km and 26 km) for the grandparent's generation to represent early times in human evolution. These estimates can serve to set parameter values of demographic models in model-based methods of prehistoric reconstruction, such as approximate Bayesian computation. Our study provides the first empirically-based estimates of human migration over multiple generations in a developing country and these estimates are intended to enable more precise reconstruction of the demographic processes that characterized human evolution.

Spinocerebellar ataxia type 10 (SCA10), an autosomal dominant cerebellar ataxia, is caused by the expansion of the non-coding ATTCT pentanucleotide repeat in the ATAXIN 10 gene. To date, all cases of SCA10 are restricted to patients with ancestral ties to Latin American countries. Here, we report on a SCA10 patient with Sioux Native American ancestry and no reported Hispanic or Latino heritage. Neurological exam findings revealed impaired gait with mild, age-consistent cerebellar atrophy and no evidence of epileptic seizures. The age at onset for this patient, at 83 years of age, is the latest documented for SCA10 patients and is suggestive of a reduced penetrance allele in his family. Southern blot analysis showed an SCA10 expanded allele of 1400 repeats. Established SNPs surrounding the SCA10 locus showed a disease haplotype consistent with the previously described "SCA10 haplotype". This case suggests that the SCA10 expansion represents an early mutation event that possibly occurred during the initial peopling of the Americas.

Studies of the impact of post-marital residence patterns on the distribution of genetic variation within populations have returned conflicting results. These studies have generally examined genetic diversity within and between groups with different post-marriage residence patterns. Here, we directly examine Y chromosome microsatellite variation in individuals carrying a chromosome in the same Y haplogroup. We analyze Y chromosome data from two samples of Yemeni males: a sample representing the entire country and a sample from a large highland village. Our results support a normative patrilocality in highland Yemeni tribal populations, but also suggest that patrilocality is violated often enough to break down the expected correlation of genetic and geographic distance. We propose that a great deal of variation in male dispersal distance distributions is subsumed under the "patrilocal" label and that few human societies are likely to realize the idealized male dispersal distribution expected under strict patrilocality. In addition, we found almost no specific correspondence between social kinship and genetic patriline at the level of the clan (large, extended patrilineal kinship group) within a large, highland Yemeni village. We discuss ethnographic accounts that offer several cultural practices that explain exceptions to patrilocality and means by which social kinship and genetic patriline may become disentangled., (Copyright © 2013 Wiley Periodicals, Inc.)