Their observations revealed an alternating occurrence of clusters containing lethal and non-lethal glycine substitutions along the gene, with three such regions present in COL1A1 and two in COL1A2. This discovery indicated that the clinical severity of OI is not only determined by the impact of the mutation on the structure or assembly of the monomer, but may also play a role in higher order interactions with multiple matrix molecules (Di Lullo et al., 2002; Sweeney et al., 2008). The gene discussed is COL1A1; the disease is osteogenesis imperfecta.