Developmental biology. From genetic association to genetic switch.

at which nucleation occurs is determined largely by the size of the nanodroplets present (10). Could the precritical clusters observed by Gebauer et al. also be the result of stabilization of calcium carbonate clusters by another species present as an impurity? This mechanism would provide a basis for stabilizing precritical clusters in a free-energy minimum and does not contradict classical nucle-ation theory. Such impurities are ubiquitous and virtually impossible to eliminate from any solution. The results of Gebauer et al. may thus reflect the mechanism of nucle-ation of calcium carbonate in " real " systems. Nucleation could then occur by coalescence of the precritical clusters to give ACC, which will subsequently crystallize to a more stable crystalline polymorph. The latter mechanism is consistent with the observations of Gebauer et al., who show that ACC is the first phase precipitated after nucleation. The idea that nucleation of calcium car-bonate may proceed via an aggregation mechanism is highly topical. The past decade has seen great progress in understanding crystallization processes, and it is now well recognized that single-crystal growth (as distinct from nucleation) often occurs via the aggregation of small precursor units rather than by addition of ions or molecules to a nucleus (11). Cluster species have also been observed before nucleation in saturated solutions of compounds such as sodium chloride (2), urea (12), and glycine (3), and there have been suggestions that clustering can determine which polymorph is formed (13). However, none of these even remotely approach the size or stability of the clusters observed by Gebauer et al. Further investigation of precritical clusters and their role in the crystallization of calcium carbonate, and indeed other compounds, is eagerly anticipated. 1803 PERSPECTIVES D eciphering the sequence of the human genome and the subsequent cataloging of common human DNA sequence variation marked a paradigm shift in human genetics. These resources, together with advances in cost-effective genotyping technologies, enabled the design of genome-wide association studies for the unbiased discovery of commonly occurring DNA sequence variations called single-nucleotide polymorphisms (SNPs) that are preferentially associated with a disease or other clinical trait (1). Although genome-wide association studies have uncovered disease-associated SNPs, identifying actual disease-causing variants— and gaining deep insights into how those variants generate the underlying molecular patho-physiology—have so far yielded only modest results. This has led to criticisms of the genome-wide association approach for investigating the etiologies of common diseases (2). However, this assessment …