North and East African mitochondrial genetic variation needs further characterization towards precision medicine

Abstract

Mitochondria are maternally inherited cell organelles with their own genome, and perform various functions in eukaryotic cells such as energy production and cellular homeostasis. Due to their inheritance and manifold biological roles in health and disease, mitochondrial genetics serves a dual purpose of tracing the history as well as disease susceptibility of human populations across the globe. This requires a comprehensive catalogue of commonly observed genetic variations in the mitochondria for all regions throughout the world. So far, however, certain regions, such as North and East Africa have been understudied. Towards this, we have created the most comprehensive quality-controlled North and East African mitochondrial dataset to date by compiling 11 published cohorts with novel data of mitochondrial genomes from 159 Sudanese individuals. We combined these 641 mitochondrial sequences with sequences from the 1000 Genomes (n=2,504) and the Human Genome Diversity Project (n=828) and used the tool haplocheck for extensive quality control and detection of in-sample contamination. Using a subset of high-coverage mitochondrial sequences we predict 15 potentially novel haplogroups in North and East African subjects and observe likely phylogenetic deviations from the established PhyloTree reference for haplogroups L0a1 and L2a1. This demonstrates common hitherto unexplored variants in mitochondrial genomes of the North and East African region that lead to novel phylogenetic relationships, calling for further in-depth population genetic studies in that region.