Importance of human demographic history knowledge in genetic studies involving multi-ethnic cohorts [version 2; referees: 2 approved]

Paucity of data from African populations due to under-representation in human genetic studies has impeded detailed understanding of the heritable human genome variation. This is despite the fact that Africa has sizeable genetic, cultural and linguistic diversity. There are renewed efforts to understand health problems relevant to African populations using more comprehensive datasets, and by improving expertise in health-related genomics among African scientists. We emphasise that careful consideration of the sampled populations from national and within-continental cohorts in large multi-ethnic genetic research efforts is required to maximise the prospects of identifying and fine-mapping novel risk variants in indigenous populations. We caution that human demographic history should be taken into consideration in such prospective genetic-association studies

Importance of human demographic history knowledge in genetic studies involving multi-ethnic cohorts [version 3; referees: 2 approved]

Paucity of data from African populations due to under-representation in human genetic studies has impeded detailed understanding of the heritable human genome variation. This is despite the fact that Africa has sizeable genetic, cultural and linguistic diversity. There are renewed efforts to understand health problems relevant to African populations using more comprehensive datasets, and by improving expertise in health-related genomics among African scientists. We emphasise that careful consideration of the sampled populations from national and within-continental cohorts in large multi-ethnic genetic research efforts is required to maximise the prospects of identifying and fine-mapping novel risk variants in indigenous populations. We caution that human demographic history should be taken into consideration in such prospective genetic-association studies

Population genetic structure of Streptococcus pneumoniae in Kilifi, Kenya, prior to the introduction of pneumococcal conjugate vaccine.

BACKGROUND: The 10-valent pneumococcal conjugate vaccine (PCV10) was introduced in Kenya in 2011. Introduction of any PCV will perturb the existing pneumococcal population structure, thus the aim was to genotype pneumococci collected in Kilifi before PCV10. METHODS AND FINDINGS: Using multilocus sequence typing (MLST), we genotyped >1100 invasive and carriage pneumococci from children, the largest collection genotyped from a single resource-poor country and reported to date. Serotype 1 was the most common serotype causing invasive disease and was rarely detected in carriage; all serotype 1 isolates were members of clonal complex (CC) 217. There were temporal fluctuations in the major circulating sequence types (STs); and although 1-3 major serotype 1, 14 or 23F STs co-circulated annually, the two major serotype 5 STs mainly circulated independently. Major STs/CCs also included isolates of serotypes 3, 12F, 18C and 19A and each shared ≤ 2 MLST alleles with STs that circulate widely elsewhere. Major CCs associated with non-PCV10 serotypes were predominantly represented by carriage isolates, although serotype 19A and 12F CCs were largely invasive and a serotype 10A CC was equally represented by invasive and carriage isolates. CONCLUSIONS: Understanding the pre-PCV10 population genetic structure in Kilifi will allow for the detection of changes in prevalence of the circulating genotypes and evidence for capsular switching post-vaccine implementation

The Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia : design, results and future prospects

The impact of many unfavorable childhood traits or diseases, such as low birth weight and mental disorders, is not limited to childhood and adolescence, as they are also associated with poor outcomes in adulthood, such as cardiovascular disease. Insight into the genetic etiology of childhood and adolescent traits and disorders may therefore provide new perspectives, not only on how to improve wellbeing during childhood, but also how to prevent later adverse outcomes. To achieve the sample sizes required for genetic research, the Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia were established. The majority of the participating cohorts are longitudinal population-based samples, but other cohorts with data on early childhood phenotypes are also involved. Cohorts often have a broad focus and collect(ed) data on various somatic and psychiatric traits as well as environmental factors. Genetic variants have been successfully identified for multiple traits, for example, birth weight, atopic dermatitis, childhood BMI, allergic sensitization, and pubertal growth. Furthermore, the results have shown that genetic factors also partly underlie the association with adult traits. As sample sizes are still increasing, it is expected that future analyses will identify additional variants. This, in combination with the development of innovative statistical methods, will provide detailed insight on the mechanisms underlying the transition from childhood to adult disorders. Both consortia welcome new collaborations. Policies and contact details are available from the corresponding authors of this manuscript and/or the consortium websites.Peer reviewe

Comparative genomics identifies male accessory gland proteins in five Glossina species [version 2; referees: 2 approved]

Accessory gland proteins (ACPs) are important reproductive proteins produced by the male accessory glands (MAGs) of most insect species. These proteins are essential for male insect fertility, and are transferred alongside semen to females during copulation. ACPs are poorly characterized in Glossina species (tsetse fly), the principal vector of the parasite that causes life-threatening Human African Trypanosomiasis and Animal trypanosomiasis in endemic regions in Africa. The tsetse fly has a peculiar reproductive cycle because of the absence of oviposition. Females mate once and store sperm in a spermathecal, and produce a single fully developed larva at a time that pupates within minutes of exiting their uterus. This slow reproductive cycle, compared to other insects, significantly restricts reproduction to only 3 to 6 larvae per female lifespan. This unique reproductive cycle is an attractive vector control strategy entry point. We exploit comparative genomics approaches to explore the diversity of ACPs in the recently available whole genome sequence data from five tsetse fly species ( Glossina morsitans, G. austeni, G. brevipalpis, G. pallidipes and G. fuscipes). We used previously described ACPs in Drosophila melanogaster and Anopheles gambiae as reference sequences. We identified 36, 27, 31, 29 and 33 diverse ACP orthologous genes in G. austeni, G. brevipalpis, G. fuscipes, G. pallidipes and G. morsitans genomes respectively, which we classified into 21 functional classes. Our findings provide genetic evidence of MAG proteins in five recently sequenced Glossina genomes. It highlights new avenues for molecular studies that evaluate potential field control strategies of these important vectors of human and animal disease

Community-led data collection using Open Data Kit for surveillance of animal African trypanosomiasis in Shimba hills, Kenya

Abstract Objective In Sub-Saharan Africa, there is an increase in trypanosome non-susceptibility to multiple trypanocides, but limited information on judicious trypanocide use is accessible to smallholder farmers and agricultural stakeholders in disease endemic regions, resulting in widespread multi-drug resistance. Huge economic expenses and the laborious nature of extensive field studies have hindered collection of the requisite large-scale prospective datasets required to inform disease management. We examined the efficacy of community-led data collection strategies using smartphones by smallholder farmers to acquire robust datasets from the trypanosomiasis endemic Shimba hills region in Kenya. We used Open Data Kit, an open-source smartphone application development software, to create a data collection App. Results Our study provides proof of concept for the viability of using smartphone Apps to remotely collect reliable large-scale information from smallholder farmers and veterinary health care givers in resource poor settings. We show that these datasets can be reliably collated remotely, analysed, and the findings can inform policies that improve farming practices and economic wellbeing while restricting widespread multi-drug resistance. Moreover, this strategy can be used to monitor and manage other infectious diseases in other rural, resource poor settings

Antimicrobial Resistance Profiles and Genes of Staphylococci Isolated from Mastitic Cow’s Milk in Kenya

Increasing numbers of potentially zoonotic multidrug-resistant (MDR) staphylococci strains, associated with mastitis in dairy cows, are being reported globally and threaten disease management in both animal and human health. However, the prevalence and antimicrobial resistance profiles of these strains, including methicillin-resistant staphylococci (MRS), in Kenya is not well known. This study investigated the drug resistance profiles and genes carried by 183 staphylococci isolates from 142 dairy cows representing 93 farms recovered from mastitis milk of dairy cows in two selected counties in Kenya. Staphylococci isolates were characterized by phenotypic characteristics, polymerase chain reaction (PCR) amplification, partial sequencing and susceptibility testing for 10 antimicrobial drugs. Detection of seven resistance genes to the various antimicrobial drugs was conducted using PCR. Overall, phenotypic resistance among the staphylococci ranged between 66.1% for ampicillin and 3.5% for fluoroquinolones. Twenty-five percent (25%) of S. aureus and 10.8% of the coagulase-negative staphylococci (CoNS) isolates, were methicillin-resistant staphylococci phenotypically (defined as resistance to cefoxitin disk diffusion). The most common genes found in S. aureus and CoNS were blaZ and strB at 44.3% and 26%, and 78% and 50%, respectively. MDR was observed in 29.67% and 16.3% of S. aureus and CoNS, respectively. These findings pose a threat to bovine mastitis treatment and management as well as human health