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A sample of Burkina Faso Djallonké (West African Dwarf) sheep was analyzed to identify stretches of homozygous segments (runs of homozygosity; ROH) overlapping with ancient homozygosity-by-descent (HBD) segments. HBD segments were considered ancient if they were likely to be inherited from ancestors living from 1024 to 2048 generations ago, roughly coinciding with the time in which sheep entered into West Africa. It is hypothesized that such homozygous segments can inform on the effect of the sheep genome of human-mediated selection for adaptation to this harsh environment. PLINK analyses allowed to identify a total of 510 ROH segments in 127 different individuals that could be summarized into 124 different ROH. A total of 32,968 HBD segments were identified on 119 individuals using the software ZooRoH. HBD segments inherited from ancestors living 1024 and 2048 generations ago were identified on 61 individuals. The overlap between consensus ROH identified using PLINK and HBD fragments putatively assigned to generations 1024 and 2048 gave 108 genomic areas located on 17 different ovine chromosomes which were considered candidate regions for gene-annotation enrichment analyses. Functional annotation allowed to identify six statistically significant functional clusters involving 50 candidate genes. Cluster 1 was involved in homeostasis and coagulation; functional clusters 2, 3, and 6 were associated to innate immunity, defense against infections, and white blood cells proliferation and migration, respectively; cluster 4 was involved in parasite resistance; and functional cluster 5, formed by 20 genes, was involved in response to stress. The current analysis confirms the importance of genomic areas associated to immunity, disease resistance, and response to stress for adaptation of sheep to the challenging environment of humid Sub-Saharan West Africa. Full article