Genetic structure correlates with ethnolinguistic diversity in eastern and southern Africa.

African populations are the most diverse in the world yet are sorely underrepresented in medical genetics research. Here, we examine the structure of African populations using genetic and comprehensive multi-generational ethnolinguistic data from the Neuropsychiatric Genetics of African Populations-Psychosis study (NeuroGAP-Psychosis) consisting of 900 individuals from Ethiopia, Kenya, South Africa, and Uganda. We find that self-reported language classifications meaningfully tag underlying genetic variation that would be missed with consideration of geography alone, highlighting the importance of culture in shaping genetic diversity. Leveraging our uniquely rich multi-generational ethnolinguistic metadata, we track language transmission through the pedigree, observing the disappearance of several languages in our cohort as well as notable shifts in frequency over three generations. We find suggestive evidence for the rate of language transmission in matrilineal groups having been higher than that for patrilineal ones. We highlight both the diversity of variation within Africa as well as how within-Africa variation can be informative for broader variant interpretation; many variants that are rare elsewhere are common in parts of Africa. The work presented here improves the understanding of the spectrum of genetic variation in African populations and highlights the enormous and complex genetic and ethnolinguistic diversity across Africa.

Low-coverage sequencing cost-effectively detects known and novel variation in underrepresented populations.

Genetic studies in underrepresented populations identify disproportionate numbers of novel associations. However, most genetic studies use genotyping arrays and sequenced reference panels that best capture variation most common in European ancestry populations. To compare data generation strategies best suited for underrepresented populations, we sequenced the whole genomes of 91 individuals to high coverage as part of the Neuropsychiatric Genetics of African Population-Psychosis (NeuroGAP-Psychosis) study with participants from Ethiopia, Kenya, South Africa, and Uganda. We used a downsampling approach to evaluate the quality of two cost-effective data generation strategies, GWAS arrays versus low-coverage sequencing, by calculating the concordance of imputed variants from these technologies with those from deep whole-genome sequencing data. We show that low-coverage sequencing at a depth of ≥4× captures variants of all frequencies more accurately than all commonly used GWAS arrays investigated and at a comparable cost. Lower depths of sequencing (0.5-1×) performed comparably to commonly used low-density GWAS arrays. Low-coverage sequencing is also sensitive to novel variation; 4× sequencing detects 45% of singletons and 95% of common variants identified in high-coverage African whole genomes. Low-coverage sequencing approaches surmount the problems induced by the ascertainment of common genotyping arrays, effectively identify novel variation particularly in underrepresented populations, and present opportunities to enhance variant discovery at a cost similar to traditional approaches.

CA-MRSA and HA-MRSA coexist in community and hospital settings in Uganda.

Background: Methicillin resistant Staphylococcus aureus (MRSA) strains were once confined to hospitals however, in the last 20 years MRSA infections have emerged in the community in people with no prior exposure to hospitals. Strains causing such infections were novel and referred to as community-associated MRSA (CA-MRSA). The aim of this study was to determine the MRSA carriage rate in children in eastern Uganda, and to investigate coexistence between CA-MRSA and hospital-associated (HA-MRSA). Methods: Between February and October 2011, nasopharyngeal samples (one per child) from 742 healthy children under 5 years in rural eastern Uganda were processed for isolation of MRSA, which was identified based on inhibition zone diameter of ≤19 mm on 30 µg cefoxitin disk. SCCmec and spa typing were performed for MRSA isolates. Results: A total of 140 S. aureus isolates (18.9%, 140/742) were recovered from the children of which 5.7% (42/742) were MRSA. Almost all (95.2%, 40/42) MRSA isolates were multidrug resistant (MDR). The most prevalent SCCmec elements were types IV (40.5%, 17/42) and I (38.1%, 16/42). The overall frequency of SCCmec types IV and V combined, hence CA-MRSA, was 50% (21/42). Likewise, the overall frequency of SCCmec types I, II and III combined, hence HA-MRSA, was 50% (21/42). Spa types t002, t037, t064, t4353 and t12939 were detected and the most frequent were t064 (19%, 8/42) and t037 (12%, 5/42). Conclusion: The MRSA carriage rate in children in eastern Uganda is high (5.7%) and comparable to estimates for Mulago Hospital in Kampala city. Importantly, HA-MRSA (mainly of spa type t037) and CA-MRSA (mainly of spa type t064) coexist in children in the community in eastern Uganda, and due to high proportion of MDR detected, outpatient treatment of MRSA infection in eastern Uganda might be difficult.