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Eritrea is strategically located at the eastern part of the African Sahel belt over what is believed to be the original scene of modern humans evolution and dispersal. The country's peculiarity is also reflected in the presence of nine ethno-linguistic populations that speak different languages, makes it all interesting in addressing some of the significant questions pertaining to history of human expansion within and beyond the African landscape. This thesis altogether presented the first glimpse into the demographic history of the existing genetic landscape of the Eritrean populations and also reflected on the spectacular level of sequence variation and presence of ancestral haplogroups within East Africans in comparison to other African and global samples. Both phylogenetic and network analyses placed East African at the root of the human evolutionary tree and as major contributors to the out-of-Africa event. The implication of the current data to genomics, forensics, and health research, as well as the need to carry out defined studies of human genetic variation that includes more representative African populations particularly East Africans is paramount.