This narrative review summarizes evidence on the bovine β-casein (CSN2) A1/A2 polymorphism as a case study of how intensive dairy selection and global gene flow can reshape allele frequencies in ways that matter for consumers, processing and agroecological resilience. We draw together evidence from (i) population-genetic surveys of CSN2 in contrasting cattle populations, including a descriptive summary of published genotype-frequency studies; (ii) controlled human studies that separate A1-containing from A2-only dairy exposure; and (iii) dairy technology and the authenticity literature relevant to identity-preserved A2 value chains. Across intensively selected Holstein-Friesian populations, A1 was consistently present at substantial frequency (approximately one-third), whereas indigenous, beef and zebu-adjacent populations were typically A2-enriched, highlighting the role of historical breed formation and modern introgression in shaping apparent geographic and climatic patterns. Human intervention studies most consistently support improved short-term gastrointestinal tolerance with A2-only milk in susceptible individuals, while evidence for longer-horizon systemic outcomes remains mixed and insufficient for causal disease claims. Processing and analytical studies suggest that β-casein genotype can modestly affect coagulation and product behavior in a context-dependent manner and that validated proteoform quantification coupled with traceability is essential for credible A2 labeling at scale. We discuss implications for breeding programs, including staged A2 selection that avoids performance trade-offs, and emphasize governance of artificial insemination and supply-chain segregation as levers to limit inadvertent allele diffusion while supporting climate-relevant genetic resources in locally adapted breeds. Collectively, the reviewed evidence suggests that A1/A2 β-casein can be usefully interpreted within a One Health framework spanning animal genetics, dairy systems and human tolerance research.
Tóth et al. (Wed,) studied this question.