Malaria causes approximately one million fatalities per year, mostly among African children. Although highlighted by the strong protective effect of the sickle-cell trait, the full impact of human genetics on resistance to the disease remains largely unexplored. Genome-wide association (GWA) studies are designed to unravel relevant genetic variants comprehensively; however, in malaria, as in other infectious diseases, these studies have been only partly successful. Here we identify two previously unknown loci associated with severe falciparum malaria in patients and controls from Ghana, West Africa. We applied the GWA approach to the diverse clinical syndromes of severe falciparum malaria, thereby targeting human genetic variants influencing any step in the complex pathogenesis of the disease. One of the loci was identified on chromosome 1q32 within the ATP2B4 gene, which encodes the main calcium pump of erythrocytes, the host cells of the pathogenic stage of malaria parasites. The second was indicated by an intergenic single nucleotide polymorphism on chromosome 16q22.2, possibly linked to a neighbouring gene encoding the tight-junction protein MARVELD3. The protein is expressed on endothelial cells and might therefore have a role in microvascular damage caused by endothelial adherence of parasitized erythrocytes. We also confirmed previous reports on protective effects of the sickle-cell trait and blood group O. Our findings underline the potential of the GWA approach to provide candidates for the development of control measures against infectious diseases in humans.

After imputation of data of the 1000 Genomes Project into a genome-wide data set of Ghanaian tuberculosis cases and controls, we identified a resistance locus on chromosome 11p13, downstream of the Wilms' tumour 1 gene. The strongest signal was obtained at SNP rs2057178 (P = 2.63 × 10−9). Replication in Gambian, Indonesian and Russian TB case-control study groups increased the significance level to P = 2.57 × 10−11.

Mutations of the connexin 26 gene (GJB2) were studied in 365 apparently unrelated individuals with profound nonsyndromic, sensorineural hearing impairment from Ghana, West Africa. Among 121 mutated chromosomes found, 110 carried the previously described R143W mutation. A total of 6 novel mutations: L79P, V178A, R184Q, A197S, I203K, and L214P, were identified, whereby I203K was based on a dinucleotide exchange and R184Q appeared to be dominant. The GJB2 variants found in Ghana tend to comprise less nonsense and frameshift mutations and more mutations located in the C-terminal half of the molecule than the variants found in other parts of the world.

Background The true burden and geographical distribution of human Borna disease virus 1 (BoDV-1) encephalitis is unknown. All detected cases so far have been recorded in Bavaria, southern Germany. Case presentation A retrospective laboratory and epidemiological investigation of a 2017 case of fatal encephalitis in a farmer in Brandenburg, northeast Germany, demonstrated BoDV-1 as causative agent by polymerase chain reaction, immunohistochemistry and in situ hybridization. Next-generation sequencing showed that the virus belonged to a cluster not known to be endemic in Brandenburg. The investigation was triggered by a recent outbreak of animal Borna disease in the region. Multiple possible exposures were identified. The next-of-kin were seronegative. Conclusions The investigation highlights clinical awareness for human BoDV-1 encephalitis which should be extended to all areas endemic for animal Borna disease. All previously diagnosed human cases had occurred > 350 km further south. Further testing of shrews and livestock with Borna disease may show whether this BoDV-1 cluster is additionally endemic in the northwest of Brandenburg.

Mutations of the transmembrane channel-like gene 1 (TMC1) have been shown to cause autosomal dominant and recessive forms of congenital nonsyndromic deafness linked to the loci DFNA36 and DFNB7/B11, respectively. In a Sudanese pedigree affected by an apparently recessive form of nonsyndromic deafness, we performed a linkage analysis using markers covering the deafness loci DFNB1 - DFNB30. A two-point LOD score of 3.08 was obtained at marker position D9S1876, located within the first intron of the TMC1 gene at DFNB7/B11. By DNA sequencing of TMC1 exons 3-22, we identified the structural variant c.1165C>T in exon 13, leading to the stop codon p.Arg389X, and the splice-site variant c.19+5G>A, independently segregating with the deafness phenotype. The c.1165C>T [p.Arg389X] mutation was also observed in four out of 243 unrelated deaf Sudanese individuals, but none of the mutations was found among 292 normal hearing controls. The finding of TMC1 mutations contributing to deafness in Sudan confirms and extends previous reports on the role of TMC1 in recessive nonsyndromic deafness and shows that deafness-causing TMC1 mutations may occur in various ethnic groups.