Why are these findings important despite their apparent rarity? From a mechanistic standpoint, both the parent-of-origin effects and structural change of this chromosomal region may provide clues to the genes involved in and pathogenesis related to schizophrenia. Ingason et al. suggest that overexpression of maternally expressed imprinted genes, such as UBE3A, could cause schizophrenia (3), as proposed for autism (6). Parent-of-origin effects are not restricted to classic imprinting mechanisms, however, and other genes may be involved. Normally, for example, the GABAA receptor subunit genes GABRB3, GABRA5, and GABRG3 (Figure 1) are expressed equally from maternal and paternal alleles in the frontal cortex (6, 8). There is genetic evidence implicating GABRB3 in autism, including association of a rare coding sequence variant when it is maternally transmitted (9). Importantly, dosage imbalance in the 15q11.2-q13.3 region can disrupt normal parental homologue pairing, DNA methylation patterns, and gene expression in this region during development of neurons (6, 10). This process of homologue pairing of chromosome 15 requires binding of the MECP2-methylated DNA binding protein to sites across the 15q11.2-q13.3 region (6, 8). Recent studies implicate fascinating epigenetic mechanisms involving this product of the MECP2 gene, mutations of which cause Rett syndrome (MIM 312750). MECP2 deficiency has been shown to reduce expression of GABRB3 as well as UBE3A (8, 10). Studies of gene expression in brain tissue unrelated to 15q11-q13 anomalies suggest the tantalizing possibility of broader applicability (6, 10). Mouse- and human-induced pluripotent stem cell models may help further our understanding of a possible shared molecular pathway for autism and schizophrenia (2).