sub-Saharan African Groups Research Articles

Characterization of CYP2B6 and CYP2A6 Pharmacogenetic Variation in Sub-Saharan African Populations.

Genetic variation in CYP2B6 and CYP2A6 is known to impact interindividual response to antiretrovirals, nicotine, and bupropion, among other drugs. However, the full catalogue of clinically relevant pharmacogenetic variants in these genes is yet to be established, especially across African populations. This study therefore aimed to characterize the star allele (haplotype) distribution in CYP2B6 and CYP2A6 across diverse and understudied sub-Saharan African (SSA) populations. We called star alleles from 961 high-depth full genomes using StellarPGx, Aldy, and PyPGx. In addition, we performed CYP2B6 and CYP2A6 star allele frequency comparisons between SSA and other global biogeographical groups represented in the new 1000 Genomes Project high-coverage dataset (n = 2,000). This study presents frequency information for star alleles in CYP2B6 (e.g., *6 and *18; frequency of 21-47% and 2-19%, respectively) and CYP2A6 (e.g., *4, *9, and *17; frequency of 0-6%, 3-10%, and 6-20%, respectively), and predicted phenotypes (for CYP2B6), across various African populations. In addition, 50 potentially novel African-ancestry star alleles were computationally predicted by StellarPGx in CYP2B6 and CYP2A6 combined. For each of these genes, over 4% of the study participants had predicted novel star alleles. Three novel star alleles in CYP2A6 (*54, *55, and *56) and CYP2B6 apiece, and several suballeles were further validated via targeted Single-Molecule Real-Time resequencing. Our findings are important for informing the design of comprehensive pharmacogenetic testing platforms, and are highly relevant for personalized medicine strategies, especially relating to antiretroviral medication and smoking cessation treatment in Africa and the African diaspora. More broadly, this study highlights the importance of sampling diverse African ethnolinguistic groups for accurate characterization of the pharmacogene variation landscape across the continent.

Variation in Seeking Care for Cardiovascular Disease and Ambulance Utilization among Migrants in Australia: Time, Ethnicity, and Delay (TED) Study III.

Insight into differences in seeking medical care for chest pain among migrant populations is limited. This study aimed to determine ethnic differences in seeking care behaviors and using ambulances among migrants compared to an Australian-born group. A total of 607 patients presenting with chest pain to a tertiary hospital between 1 July 2012 and 30 June 2014 were randomly selected. Data from the emergency department dataset and medical record reviews were collected and linked for analysis. The migrant group was stratified into nine ethnic groups for analysis based on the Australian Standard Classification of Cultural and Ethnic Groups. The overall median prehospital delay time was 3.7 (1.5, 10.7) h, which ranged from 2.5 (1.0, 10.7) (Southern and Eastern European group) to 6.0 (2.3, 20.6) (Sub-Saharan African group). The median decision time was 2.0 (0.8, 7.9) h, which ranged from 1.5 (Australian-born group) to 4.5 h (Sub-Saharan African group). Five ethnic groups had significantly longer decision times compared to the Australian-born group. Decision time accounted for 58.4% of pre-hospital delay time. Migrant patients were 60% less likely to seek care for chest pain within one hour (odds ratio 0.40, (0.23–0.68), p = 0.001). There was no significant difference in ambulance utilization between migrant and Australian-born groups. In conclusion, ethnic differences in seeking care for chest pain do exist, and ethnicity plays a vital role in a longer delay in seeking care. To reduce the delays and improve patient outcomes, appropriate health campaigns focusing on ethnic differences among migrant populations and normalizing cultural competency into practice are recommended.

Comparison of sequencing data processing pipelines and application to underrepresented African human populations

BackgroundPopulation genetic studies of humans make increasing use of high-throughput sequencing in order to capture diversity in an unbiased way. There is an abundance of sequencing technologies, bioinformatic tools and the available genomes are increasing in number. Studies have evaluated and compared some of these technologies and tools, such as the Genome Analysis Toolkit (GATK) and its “Best Practices” bioinformatic pipelines. However, studies often focus on a few genomes of Eurasian origin in order to detect technical issues. We instead surveyed the use of the GATK tools and established a pipeline for processing high coverage full genomes from a diverse set of populations, including Sub-Saharan African groups, in order to reveal challenges from human diversity and stratification.ResultsWe surveyed 29 studies using high-throughput sequencing data, and compared their strategies for data pre-processing and variant calling. We found that processing of data is very variable across studies and that the GATK “Best Practices” are seldom followed strictly. We then compared three versions of a GATK pipeline, differing in the inclusion of an indel realignment step and with a modification of the base quality score recalibration step. We applied the pipelines on a diverse set of 28 individuals. We compared the pipelines in terms of count of called variants and overlap of the callsets. We found that the pipelines resulted in similar callsets, in particular after callset filtering. We also ran one of the pipelines on a larger dataset of 179 individuals. We noted that including more individuals at the joint genotyping step resulted in different counts of variants. At the individual level, we observed that the average genome coverage was correlated to the number of variants called.ConclusionsWe conclude that applying the GATK “Best Practices” pipeline, including their recommended reference datasets, to underrepresented populations does not lead to a decrease in the number of called variants compared to alternative pipelines. We recommend to aim for coverage of > 30X if identifying most variants is important, and to work with large sample sizes at the variant calling stage, also for underrepresented individuals and populations.

Surviving mothers and lost babies - burden of stillbirths and neonatal deaths among women with maternal near miss in eastern Ethiopia: a prospective cohort study.

BackgroundAlthough maternal near miss (MNM) is often considered a ‘great save’ because the woman survived life-threatening complications, these complications may have resulted in loss of a child or severe neonatal morbidity. The objective of this study was to assess proportion of perinatal mortality (stillbirths and early neonatal deaths) in a cohort of women with MNM in eastern Ethiopia. In addition, we compared perinatal outcomes among women who fulfilled the World Health Organization (WHO) and the sub-Saharan African (SSA) MNM criteria.MethodsIn a prospective cohort design, women with potentially life-threatening conditions (PLTC) (severe postpartum hemorrhage, severe pre-(eclampsia), sepsis/severe systemic infection, and ruptured uterus) were identified every day from January 1st, 2016, to April 30th, 2017, and followed until discharge in the two main hospitals in Harar, Ethiopia. Maternal and perinatal outcomes were collected using both sets of criteria. Numbers and proportions of stillbirths and early neonatal deaths were computed and compared.ResultsOf 1054 women admitted with PTLC during the study period, 594 women fulfilled any of the MNM criteria. After excluding near misses related to abortion, ectopic pregnancy or among undelivered women, 465 women were included, in whom 149 (32%) perinatal deaths occurred: 132 (88.6%) stillbirths and 17 (11.4%) early neonatal deaths. In absolute numbers, the SSA criteria picked up more perinatal deaths compared to the WHO criteria, but the proportion of perinatal deaths was lower in SSA group compared to the WHO (149/465, 32% vs 62/100, 62%). Perinatal mortality was more likely among near misses with antepartum hemorrhage (adjusted odds ratio (aOR) = 4.81; 95% CI = 1.76-13.20), grand multiparous women (aOR = 4.31; 95% confidence interval CI = 1.23-15.25), and women fulfilling any of the WHO near miss criteria (aOR = 4.89; 95% CI = 2.17-10.99).ConclusionWHO MNM criteria pick up fewer perinatal deaths, although perinatal mortality occurred in a larger proportion of women fulfilling the WHO MNM criteria compared to the SSA MNM criteria. As women with MNM have increased risk of perinatal deaths (in both definitions), a holistic care addressing the needs of the mother and baby should be considered in management of women with MNM.

An unexpected world population variation of MCT1 polymorphism 1470T > A involved in lactate transport

ABSTRACTA common missense mutation (1470T > A) in gene SLC16A1 responsible for an amino acid substitution in protein MCT1 has been associated with differential lactate transport and hence, differences in physical performance and muscle injuries in relation to physical exercise. This study describes, for the first time, the worldwide variation of MCT1 variant 1470T > A at an intra- and inter-continental level. Two thousand five hundred and four individual genotypes of 26 populations clustered in 5 population groups have been analysed with data downloaded from the public database 1000 Genomes Phase 3 Browser. Several parameters of population differentiation and structure have been explored as well as selection signatures in the whole gene. Allele T, the common variant, shows extremely high values in Sub-Saharan African groups (frequencies 86–91%) as compared with the remaining world regions (69–49%). TT genotype also predominates in African groups, showing significant differences with the rest of world populations. In view of the evidence that the TT genotype is associated with clinical implications and a better predisposition to sprint/power performances, we suggest that the high presence of the TT genotype in African populations should be taken into account in future association studies at both medical and sports fields.

RETRACTED: Gaining ethnoarchaeological insight into prehistoric southern African pigment mining practices

Abstract Although the exploitation of ochre and its role in the emergence of modern human behaviour has been afforded substantial academic consideration, inquiries into ochre procurement strategies remain limited. Since the systematic exploitation of red ochre is widely viewed as symptomatic of increasing cognitive complexity, the persistence of this behaviour amongst extant sub-Saharan African groups is significant in terms of human behavioural aspects observed in the archaeological record. The aim of this paper is to provide insight into prehistoric ochre procurement strategies by presenting an account of the methods implicated in the extraction of red ochre by the Ovahimba of the Kunene Region, north-western Namibia. I draw correlations between prehistoric and modern traditional mining practices and show that ethnoarchaeological research provides a basis for the formulation and assessment of archaeological research questions. I focus on the primary source of red ochre in the Kunene Region, the Ombumbuu ochre quarries, and employ visible spectroscopy, energy-dispersive X-ray fluorescence (ED-XRF), X-ray diffraction (XRD) and scanning electron microscopy and energy dispersive X-ray spectrometry (SEM-EDS) to characterise ochre from this resource. I also explore the evolutionary impact that the habitual exploitation of red ochre might have had on prehistoric human adaptive strategies and assert that these played an important role in increasing human survivability and cumulative cultural capacity.

Admixture into and within sub-Saharan Africa.

Similarity between two individuals in the combination of genetic markers along their chromosomes indicates shared ancestry and can be used to identify historical connections between different population groups due to admixture. We use a genome-wide, haplotype-based, analysis to characterise the structure of genetic diversity and gene-flow in a collection of 48 sub-Saharan African groups. We show that coastal populations experienced an influx of Eurasian haplotypes over the last 7000 years, and that Eastern and Southern Niger-Congo speaking groups share ancestry with Central West Africans as a result of recent population expansions. In fact, most sub-Saharan populations share ancestry with groups from outside of their current geographic region as a result of gene-flow within the last 4000 years. Our in-depth analysis provides insight into haplotype sharing across different ethno-linguistic groups and the recent movement of alleles into new environments, both of which are relevant to studies of genetic epidemiology.

Response to the critique of “Keratocystic odontogenic tumor: systematic review with analysis of 72 additional cases from Mumbai, India”

Response to the critique of “Keratocystic odontogenic tumor: systematic review with analysis of 72 additional cases from Mumbai, India”

Molecular characterization of genetic diversity within the Africa/Middle East/Asia Minor and Sub-Saharan African groups of the Bemisia tabaci species complex

Bemisia tabaci Gennadius is a major plant pest in many agricultural systems worldwide. It is a complex of cryptic species that differ in many ecological respects, including damage-causing potential. Monitoring the genetic composition of B. tabaci populations in the field is, therefore, essential for achieving effective control. Sequencing is costly and time consuming; thus, efficient diagnostic tools must be developed to perform epidemiological studies involving hundreds of individuals. Here, we describe a polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP) method for identifying all the putative species comprising the Africa/Middle East/Asia Minor group, including those that are the most devastating crop pests. Moreover, intra-specific diversity associated with specific symbiotic bacteria known to manipulate insect host phenotypes can also be detected. In addition, this method discriminates between the Africa/Middle East/Asia Minor and the Sub-Saharan African groups, which are sympatric in some areas. This simple, reliable and cost-effective diagnostic tool is ideal for the rapid analysis of a high number of individuals and, thus, has potential applications in field contexts, where it could provide valuable baseline information for pest management programs.

Prevalence, awareness, treatment, and control of hypertension among Ghanaian population in Amsterdam, the Netherlands: the GHAIA study

Migration from sub-Saharan Africa to industrialized countries has increased tremendously over the last few decades, yet very little is known about the health status of sub-Saharan African populations living in industrialized communities. The aim of this study was to assess prevalence, levels of awareness, treatment, and control of hypertension among the largest sub-Saharan African group (Ghanaians) living in the Netherlands. Cross-sectional study of Ghanaian adults aged 18-60 years in Amsterdam, the Netherlands. The overall prevalence of hypertension was 55%. Of these, about half were aware of their condition, 45% were receiving antihypertensive medication, and 15% were controlled (blood pressure <140/90 mmHg). The prevalence rates of hypertension, awareness, and treatment were similar among males and females. However, males had a lower blood pressure control rate than females. Among all hypertensives, 22% of females had their blood pressure controlled compared with 5.8% in males: adjusted prevalence ratio (APR) 3.94 (95% CI 1.05-14.79). Among those receiving treatment for their hypertension, 48% of females were controlled compared with only 13% of males: APR 4.08 (95% CI 1.20-13.87). Hypertension is a major problem among this recently migrated sub-Saharan African population. Furthermore, hypertension control rate is very low particularly in males. Urgent measures are needed to halt the increasing prevalence of hypertension and to improve hypertension control among these populations.

Natural selection among Eurasians at genomic regions associated with HIV-1 control

BackgroundHIV susceptibility and pathogenicity exhibit both interindividual and intergroup variability. The etiology of intergroup variability is still poorly understood, and could be partly linked to genetic differences among racial/ethnic groups. These genetic differences may be traceable to different regimes of natural selection in the 60,000 years since the human radiation out of Africa. Here, we examine population differentiation and haplotype patterns at several loci identified through genome-wide association studies on HIV-1 control, as determined by viral-load setpoint, in European and African-American populations. We use genome-wide data from the Human Genome Diversity Project, consisting of 53 world-wide populations, to compare measures of FST and relative extended haplotype homozygosity (REHH) at these candidate loci to the rest of the respective chromosome.ResultsWe find that the Europe-Middle East and Europe-South Asia pairwise FST in the most strongly associated region are elevated compared to most pairwise comparisons with the sub-Saharan African group, which exhibit very low FST. We also find genetic signatures of recent positive selection (higher REHH) at these associated regions among all groups except for sub-Saharan Africans and Native Americans. This pattern is consistent with one in which genetic differentiation, possibly due to diversifying/positive selection, occurred at these loci among Eurasians.ConclusionsThese findings are concordant with those from earlier studies suggesting recent evolutionary change at immunity-related genomic regions among Europeans, and shed light on the potential genetic and evolutionary origin of population differences in HIV-1 control.

Glandular odontogenic cyst: systematic review

The aim of this study was to evaluate the principal features of "glandular odontogenic cyst" (GOC), by systematic review (SR), and to compare their frequencies among four global groups. The databases searched were the PubMed interface of MEDLINE and LILACS. Only those reports of GOCs that occurred in a series in the reporting authors' caseload were considered. All cases were confirmed histopathologically. 18 reports on 17 series of consecutive cases were included in the SR. GOC affected males twice as frequently and the mandible almost three times as frequently. The mean age at first presentation was 44 years, coincident with that of the Western global group, in which the largest proportion of reports and cases first presented in the second half of the fifth decade. However, age at presentation of GOCs in the East Asian and sub-Saharan African global groups was nearly a decade younger, this was significant. Six reports included details of at least one clinical presentation. Eight reports included at least one conventional radiological feature. There were some significant differences between global groups. The Western global group had a particular predilection for the anterior sextants of both jaws. The sub-Saharan African group displayed buccolingual expansion (as did the Latin American group) and tooth displacement in every case. 18% of GOCs recurred overall, except in the sub-Saharan African global group. GOCs have a marked propensity to recur in most global groups. GOCs presented in older patients and with swellings, affected the anterior sextants of both jaws, and radiologically were more likely to present as a well-defined unilocular radiolucency with buccolingual expansion. Tooth displacement, root resorption and an association with unerupted teeth occurred in 50%, 30% and 11% of cases, respectively.

Genetic testing improves the diagnosis of adult type hypolactasia in the Mediterranean population of Sardinia

Recently, the C/T-13910 polymorphism on chromosome 2q21 in North-European populations has been found completely associated with lactase activity and its genetic typing proposed as first-stage screening test for adult hypolactasia. However, the C/T-13910 variant in some sub-Saharan African groups is not a predictor of lactase persistence. In this work, we wanted to verify if in the Mediterranean island of Sardinia, located in Southern Europe, the C/T-13910 polymorphism may be useful or not for the diagnosis of adult type hypolactasia. Validation study of a genetic testing for adult type hypolactasia in Sardinians. Brotzu Hospital and Microcitemico Hospital, Cagliari, Italy. The sample consisted in 84 Sardinian individuals (63 women and 21 men; range 20-73 years) selected from a group of 832 patients. Genetic testing was compared to an improved test obtained by a combination of different breath hydrogen tests and clinical assessment. We found that all 49 individuals with lactose malabsorption, demonstrated by a combination of different breath hydrogen tests and clinical assessment, carried the C/C-13910 genotype associated with lactase non-persistence, 23 individuals with lactose normal absorption carried the C/T-13910 genotype associated with lactase persistence and only one person with the above phenotype showed a discordant C/C-13910 genotype. The genetic testing showed very high sensitivity, specificity, positive and negative predictive values of 100, 95.8, 98 and 100%, respectively. Sardinians, unlike some ethnic groups in sub-Saharan Africa, show the same genetic association of hypolactasia with the C/T-13910 variant as other North-European populations. The genetic testing for the C/T-13910 variant may contribute to improving the diagnosis of adult type hypolactasia.

Bodily pain and associated mental distress among immigrant adolescents

The aim of this study was to describe differences among immigrant groups in bodily pain, and analyze its association with mental distress. A population-based cross-sectional study was carried out involving tenth grade pupils in Oslo. Of the 7,343 pupils that participated, one-quarter were first- or second-generation immigrants. The Hopkins Symptom Checklist-10 was used to measure mental distress. All information on pain and mental distress was self-reported. Girls reported more bodily pain from all types of pain. Headache was the most prevalent pain site across gender and immigrant groups. Strong associations between mental distress and number of pain sites were found for all immigrant groups. Neck and shoulder pain yielded the highest odds ratio (OR) for mental distress among the majority of the immigrant groups. The Sub-Saharan African group had the highest adjusted OR for mental distress [OR=9.8 (1.1-82.7)] when reporting three or more pain sites, and the Indian Subcontinent the lowest [OR=4.0 (1.8-8.8)]. The differences in number and types of pain were small, though significant between the different immigrant groups. Adolescents from Sub-Saharan Africa seem to react with more mental distress to bodily pain than adolescents emigrating from the Indian Subcontinent.

Finger ridge‐count variation among various Subsaharan African groups

AbstractThis paper addresses the question of the extent to which finger ridge‐count data are useful features with which to study population variation in Subsaharan Africa. Each subject was represented by a vector of 20 ridge‐counts, a radial and an ulnar count for each digit. Such data were available from 11 African groups, nine of which were indigenous Africans, and two, the South African Colored and South African Indians, contained a portion of non‐African ancestory. The ridge‐counts were first transformed to principal component scores and these were subjected to multivariate analysis of variance and distance analysis to elucidate intergroup variation. The primary findings were that ridgecounts provide a good reflection of variation on at least two levels, that of African versus non‐African, and variation among Africans. Also, the principal components that reveal variation at these two levels are very different. We conclude that ridge‐counts can only be useful in population studies if full account is taken of their multicomponent nature.