In the frame of the workshop and training session organized for the European IMAGE project, I will dedicate my presentation on positional cloning strategy aiming at the identification of causal mutations involved in the genetic determinism of traits of interest. After a brief overview of the global approach (genome-wide association study, linkage analysis, haplotype phasing…), I will focus my talk on two examples of successful stories leading to the characterization of molecular mechanisms regulating either reproduction or robustness in sheep. In 2013, we identified 2 novel causal BMP15 mutations associated with hyperprolificacy in sheep and showed their drastic effect on the BMP15 signaling pathway. This study extended the spectrum of mutations within the BMP15 ovine gene and clearly complicated the range of action of BMP15 in the folliculogenesis and control of ovulation rate (https://doi.org/10.1371/journal.pgen.1003482). In 2017, we determined the mutation responsible of the crimped hair (wool) exhibited by most of modern domesticated sheep like the well-known Merino sheep. We reported the original molecular mechanism underlying fleece variation in sheep and we showed that this causal mutation perfectly discriminates ancestral hairy sheep species from domestic modern wooly sheep breeds (https://doi.org/10.1093/molbev/msx114).