Opposing brain differences in 16p11.2 deletion and duplication carriers.

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TitleOpposing brain differences in 16p11.2 deletion and duplication carriers.
Publication TypeJournal Article
Year of Publication2014
AuthorsQureshi, AY, Mueller, S, Snyder, AZ, Mukherjee, P, Berman, JI, Roberts, TPL, Nagarajan, SS, Spiro, JE, Chung, WK, Sherr, EH, Buckner, RL
Corporate AuthorsSimons VIP consortium
JournalJ Neurosci
Date Published2014 Aug 20
KeywordsAdolescent, Adult, Age Factors, Brain, Child, Child Development Disorders, Pervasive, Chromosome Deletion, Chromosome Duplication, Chromosomes, Human, Pair 16, Cognition Disorders, Female, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Middle Aged, Neuropsychological Tests, Psychiatric Status Rating Scales, Social Behavior Disorders, Young Adult

Deletions and duplications of the recurrent ~600 kb chromosomal BP4-BP5 region of 16p11.2 are associated with a broad variety of neurodevelopmental outcomes including autism spectrum disorder. A clue to the pathogenesis of the copy number variant (CNV)'s effect on the brain is that the deletion is associated with a head size increase, whereas the duplication is associated with a decrease. Here we analyzed brain structure in a clinically ascertained group of human deletion (N = 25) and duplication (N = 17) carriers from the Simons Variation in Individuals Project compared with age-matched controls (N = 29 and 33, respectively). Multiple brain measures showed increased size in deletion carriers and reduced size in duplication carriers. The effects spanned global measures of intracranial volume, brain size, compartmental measures of gray matter and white matter, subcortical structures, and the cerebellum. Quantitatively, the largest effect was on the thalamus, but the collective results suggest a pervasive rather than a selective effect on the brain. Detailed analysis of cortical gray matter revealed that cortical surface area displays a strong dose-dependent effect of CNV (deletion > control > duplication), whereas average cortical thickness is less affected. These results suggest that the CNV may exert its opposing influences through mechanisms that influence early stages of embryonic brain development.

Alternate JournalJ Neurosci
PubMed ID25143601
PubMed Central IDPMC4138332
Grant ListR25 NS065743 / NS / NINDS NIH HHS / United States
5R25NS065743 / NS / NINDS NIH HHS / United States
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