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Pathway of Discovery of the GPR54 Gene, Mutations in its Sequence Leading to GnRH Deficiency in the Human, and Animal Knock-outs as Occurred in Reference 12. A pedigree (lower left) led to linkage (upper left) which led to demonstration of a biologic defect in the (then) candidate gene, GPR54, (upper right) which led to animal knock-outs (lower right) that demonstrated hypogonadism (lower center).
