Aspects of the present invention provide novel compositions and methods based on novel calpastatin (CAST) genetic markers, such as missense mutations in exon 3 that result in G48D or P52L substitutions (NM_174003.2:c.271G>A and 283C>T), a G/T substitution in intron 3 (AAFC02060381.1:g.2110G>T) and a GAAA repeat in intron 8 (AAFC02060381.1:g.6700[(GAAA)4]+[(GAAA)5]. Particular aspects provide novel markers for fertility (e.g., daughter pregnancy rate, DPR) and longevity (e.g., productive life, PL) in, for example, dairy cattle. Additional aspects provide for novel methods comprising marker-assisted selection to improve fertility and/or longevity in dairy cattle. Therefore, in particular embodiments, a combination of genetic selection based on one or more of the novel CAST markers, and high PTA potentials of milk production traits, provides for improved reproductive traits in association with continued high milk production traits. Further aspects disclose a previously unrecognized XL domain in the human CAST gene, and thus provide for the use of human CAST XL domain mutants/variants as markers for human fertility and longevity.