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Relating copy-number variants to head and brain size in neuropsychiatric disorders

Jonathan Sebat, Ph.D.
University of California, San Diego


Copy-number variants (CNVs) are segments of DNA that vary in copy-number between different individuals. Certain CNVs confer significant risk of neuropsychiatric disorders, including autism and schizophrenia. Notably, there appears to be a reciprocal relationship between copy-number and brain size for certain genetic loci. For example, deletions of the genomic region 16p11.2 tend to be associated with autism and increased head circumference, whereas duplications of the same segment tend to be associated with schizophrenia and smaller head circumference. These differing psychiatric phenotypes may reflect quantitative differences in how neurobiological processes are influenced by genetic variation.

Jonathan Sebat and his team are investigating how autism- and schizophrenia-associated CNVs influence craniofacial features and brain volume. They plan to screen a large clinical pediatric cohort of 1,000 subjects for CNVs known to be associated with neuropsychiatric disease. The researchers also aim to identify novel variants associated with head circumference. Sebat’s team plans to recall this group of patients for neuroimaging studies and psychiatric evaluations, including standardized diagnostic measures for autism, pediatric schizophrenia and other childhood neuropsychiatric disorders.

Changes in brain volume may be a common characteristic in people with autism- and schizophrenia-associated CNVs. These mutations might account, in part, for changes in brain anatomy observed in a variety of neuropsychiatric patient groups. The researchers’ analysis of head and brain size as it relates to CNVs may help to elucidate underlying brain alterations in a range of related disorders.