Polygenic risk scores for disease risk prediction in Africa: current challenges and future directions.

Early identification of genetic risk factors for complex diseases can enable timely interventions and prevent serious outcomes, including mortality. While the genetics underlying many Mendelian diseases have been elucidated, it is harder to predict risk for complex diseases arising from the combined effects of many genetic variants with smaller individual effects on disease aetiology. Polygenic risk scores (PRS), which combine multiple contributing variants to predict disease risk, have the potential to influence the implementation for precision medicine. However, the majority of existing PRS were developed from European data with limited transferability to African populations. Notably, African populations have diverse genetic backgrounds, and a genomic architecture with smaller haplotype blocks compared to European genomes. Subsequently, growing evidence shows that using large-scale African ancestry cohorts as discovery for PRS development may generate more generalizable findings. Here, we (1) discuss the factors contributing to the poor transferability of PRS in African populations, (2) showcase the novel Africa genomic datasets for PRS development, (3) explore the potential clinical utility of PRS in African populations, and (4) provide insight into the future of PRS in Africa.

African Global Representation in Biomedical Sciences.

African populations are diverse in their ethnicity, language, culture, and genetics. Although plagued by high disease burdens, until recently the continent has largely been excluded from biomedical studies. Along with limitations in research and clinical infrastructure, human capacity, and funding, this omission has resulted in an underrepresentation of African data and disadvantaged African scientists. This review interrogates the relative abundance of biomedical data from Africa, primarily in genomics and other omics. The visibility of African science through publications is also discussed. A challenge encountered in this review is the relative lack of annotation of data on their geographical or population origin, with African countries represented as a single group. In addition to the abovementioned limitations,the global representation of African data may also be attributed to the hesitation to deposit data in public repositories. Whatever the reason, the disparity should be addressed, as African data have enormous value for scientists in Africa and globally.

Potato oxysterol binding protein and cathepsin B are rapidly up-regulated in independent defence pathways that distinguish R gene-mediated and field resistances to Phytophthora infestans.

SUMMARY Suppression subtractive hybridization was used to isolate the genes which are specifically up-regulated in the biotrophic phase of the incompatible interaction between a potato genotype, 1512 c(16), containing the resistance gene R2, and a Phytophthora infestans isolate containing the avirulence gene Avr2. Eight cDNAs were up-regulated in the biotrophic phase of the incompatible interaction. Seven of these were also up-regulated in the compatible interaction, but not until late in the necrotrophic phase. Amongst the sequences to be isolated were genes encoding the cysteine protease cathepsin B, StCathB, and an oxysterol binding protein, StOBP1; equivalent genes are involved in programmed cell death (PCD) processes in animals, but have yet to be implicated in such processes in plants. Whereas StOBP1 was up-regulated early in potato plants containing either R gene-mediated or moderate to high levels of field resistance, the highest levels of up-regulation of StCathB were observed early in R gene-mediated resistance but gradually increased from the early to late stages of field resistance, revealing these genes to be components of independent defence pathways and providing a means of distinguishing between these forms of resistance. StOBP1 was up-regulated by oligogalacturonides (plant cell wall breakdown products generated by pectinase activities), indicating that it is also a component of a general, non-specific defence pathway and is unlikely to play a role in PCD. In contrast, the expression of StCathB was unaffected by oligogalacturonide treatment, further associating its up-regulation specifically with the gene-for-gene interaction.