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Although cassava is a major food security crop for rural communities, its production in Togo is seriously constrained by Cassava Mosaic Disease (CMD), a disease caused by begomoviruses transmitted by the whitefly (Bemesia tabaci). This study was undertaken to characterize cultivated cassava and develop high yielding CMD resistant varieties in Togo. A Participatory Rural Appraisal (PRA) was conducted to assess farmers’ perceptions of CMD, cassava production constraints, and preference criteria. Though there were some few exceptions among agroecologies, PRA results revealed that farmers perceived inadequate capital, cassava mosaic disease, deterioration of cassava roots after harvest, inadequate processing methods and the non-availability of clean cassava planting materials to be the prime constraints to cassava production. The investigations on farmers’ preferences revealed that yield, early maturity, resistance to pest and disease, delayed deterioration of roots after harvest, dry matter content, poundability and taste were the most valued selection criteria by farmers. In the survey area, CMD was perceived as the major disease causing yield losses, and various causes and management practices were associated with the disease. Genetic diversity in a panel of 149 accessions from Togo, Ghana, Brazil and International Institute of Tropical Agriculture, was explored to assess the level of phenotypic and molecular diversity present, and, subsequently, estimate the variance components, heritability and genetic advance from selecting best accessions within the germplasm for disease and agronomic traits. Multiple Correspondence Analysis showed that the most diverse qualitative traits were petiole colour, leaf colour, colour of leaf vein, flowering ability, seed set ability, levels of branching, colour of end branches, colour of stem epidermis, leaf lobe margins, and the growth habit of stem. Moreover, Principal Component Analysis underscored traits such as fresh root yield, number of roots per plant, plant vigour, aboveground biomass, CMD severity, Cassava Bacterial Blight severity (CBB), length of leaf lobe, width of leaf lobe, petiole length, plant height, height to first branching, and the harvest index as mostly contributing to the germplasm variability. Ten phenotypic clusters with interesting features such as CMD and CBB resistance, vigorous plant growth, high canopy and fresh root yield, high harvest index and high root dry matter content were identified through cluster and canonical analyses. Overall, moderate to high diversity coefficient of 0.48 and 0.78 was observed among the accessions using agromorphological and SNP markers, respectively; and the proportion of heterozygous accessions varied from 0.11 to 0.32. AMOVA revealed that only 1.1% of the genetic variation was due to the geographical origin of the accessions. Three genotypic groups and sixty duplicate accessions were detected based on SNPs profile. Ten parent genotypes comprising four farmers’ preferred cultivars susceptible to CMD with various flesh colour, two varieties from IITA and four varieties with CMD2 gene introduced from the CRI-Kumasi were crossed in a NCII mating design at Fumesua to develop F1 CMD resistant populations and, subsequently, to evaluate the performances of these populations for agronomic traits and CMD resistance; and to estimate variance components, heritability and genetic gain from breeding. In total, 24 F1 segregating families composed of 2850 progenies were developed and screened in a seedling evaluation trial conducted at Davié Research station in an alpha lattice design with four replications. The results revealed considerable amount of variability within and among families for diseases and agronomic traits under selection. The most diverse traits contributing to the families’ variability were CMD resistance, plant vigour, number of roots per plant, number of commercial roots per plant, above ground biomass, fresh root yield, harvest index and the root dry matter content. High heritability, and genetic advance expectations were observed for most of the disease and agronomic traits. There was high genetic variability among the F1 seedling populations, with great potential for selection of a group of genotypes to be used either as varieties or for hybridization.