We use genomic and transcriptomic analysis to identify candidate causal mutations in families with hereditary female infertility. Using various genome engineering methods, we generate Drosophila models of the mutations which enable us to experimentally evaluate the role of the specific mutations and the affected genes in women’s fertility. These model systems allow us to further investigate the genetic network and signaling pathways involved in ovarian development and failure. These findings will allow us to develop kits for identifying carriers of relevant genetic diseases as part of family planning counseling and will pave the way for future potential therapeutic targets and treatments for female infertility.