Domain-Specific Cognitive Impairments in Humans and Flies With Reduced CYFIP1 Dosage.

Details

Serval ID
serval:BIB_6ED830B0747E
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Domain-Specific Cognitive Impairments in Humans and Flies With Reduced CYFIP1 Dosage.
Journal
Biological psychiatry
Author(s)
Woo Y.J., Kanellopoulos A.K., Hemati P., Kirschen J., Nebel R.A., Wang T., Bagni C., Abrahams B.S.
ISSN
1873-2402 (Electronic)
ISSN-L
0006-3223
Publication state
Published
Issued date
15/08/2019
Peer-reviewed
Oui
Volume
86
Number
4
Pages
306-314
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Deletions encompassing a four-gene region on chromosome 15 (BP1-BP2 at 15q11.2), seen at a population frequency of 1 in 500, are associated with increased risk for schizophrenia, epilepsy, and other common neurodevelopmental disorders. However, little is known in terms of how these common deletions impact cognition.
We used a Web-based tool to characterize cognitive function in a novel cohort of adult carriers and their noncarrier family members. Results from 31 carrier and 38 noncarrier parents from 40 families were compared with control data from 6530 individuals who self-registered on the Lumosity platform and opted in to participate in research. We then examined aspects of sensory and cognitive function in flies harboring a mutation in Cyfip, the homologue of one of the genes within the deletion. For the fly studies, 10 or more groups of 50 individuals per genotype were included.
Our human studies revealed profound deficits in grammatical reasoning, arithmetic reasoning, and working memory in BP1-BP2 deletion carriers. No such deficits were observed in noncarrier spouses. Our fly studies revealed deficits in associative and nonassociative learning despite intact sensory perception.
Our results provide new insights into outcomes associated with BP1-BP2 deletions and call for a discussion on how to appropriately communicate these findings to unaffected carriers. Findings also highlight the utility of an online tool in characterizing cognitive function in a geographically distributed population.
Keywords
Adaptor Proteins, Signal Transducing/genetics, Adult, Animals, Chromosome Aberrations, Chromosomes, Human, Pair 15/genetics, Cognitive Dysfunction/genetics, Cognitive Dysfunction/physiopathology, Cohort Studies, Drosophila/genetics, Drosophila Proteins/genetics, Female, Genotype, Humans, Male, Middle Aged, Neurodevelopmental Disorders/genetics, Neurodevelopmental Disorders/physiopathology, Phenotype, 15q11.2, CYFIP1, Cognitive impairment, Drosophila, Neurodevelopmental disorders, Online phenotyping
Pubmed
Web of science
Create date
30/06/2019 14:51
Last modification date
07/07/2020 5:20
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