Recurrent deletions of chromosome 15q13.3 associate with intellectual disability, schizophrenia, autism and epilepsy. To gain insight into its instability, we sequenced the region in patients, normal individuals and nonhuman primates. We discovered five structural configurations of the human chromosome 15q13.3 region ranging in size from 2 to 3 Mbp. These configurations arose recently (~0.5–0.9 million years ago) as a result of human-specific expansions of segmental duplications and two independent inversion events. All inversion breakpoints map near GOLGA8 core duplicons—a ~14 kbp primate-specific chromosome 15 repeat that became organized into larger palindromic structures. GOLGA8-flanked palindromes also demarcate the breakpoints of recurrent 15q13.3 microdeletions, the expansion of chromosome 15 segmental duplications in the human lineage, and independent structural changes in apes. The significant clustering (p=0.002) of breakpoints provides mechanistic evidence for the role of this core duplicon and its palindromic architecture in promoting evolutionary and disease-related instability of chromosome 15.

Dental caries was a significant health issue for these children under 3 years of age, and factors other than bottle feeding may play an important role in its etiology. Prevention of dental caries in children under age three will depend on a better understanding of the etiology as well as improved access to care.

No abstract

Dental caries was a significant health issue for these children under 3 years of age, and factors other than bottle feeding may play an important role in its etiology. Prevention of dental caries in children under age three will depend on a better understanding of the etiology as well as improved access to care.