| Autor: |
Ionita-Laza I; Departments of Biostatistics, Psychiatry, Neuroscience, Physiology, and Cellular Biophysics, Columbia University, New York, NY 10032., Xu B, Makarov V, Buxbaum JD, Roos JL, Gogos JA, Karayiorgou M |
| Jazyk: |
angličtina |
| Zdroj: |
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2014 Jan 07; Vol. 111 (1), pp. 343-8. Date of Electronic Publication: 2013 Dec 16. |
| DOI: |
10.1073/pnas.1309475110 |
| Abstrakt: |
We used a family-based cluster detection approach designed to localize significant rare disease-risk variants clusters within a region of interest to systematically search for schizophrenia (SCZ) susceptibility genes within 49 genomic loci previously implicated by de novo copy number variants. Using two independent whole-exome sequencing family datasets and a follow-up autism spectrum disorder (ASD) case/control whole-exome sequencing dataset, we identified variants in one gene, Fanconi-associated nuclease 1 (FAN1), as being associated with both SCZ and ASD. FAN1 is located in a region on chromosome 15q13.3 implicated by a recurrent copy number variant, which predisposes to an array of psychiatric and neurodevelopmental phenotypes. In both SCZ and ASD datasets, rare nonsynonymous risk variants cluster significantly in affected individuals within a 20-kb window that spans several key functional domains of the gene. Our finding suggests that FAN1 is a key driver in the 15q13.3 locus for the associated psychiatric and neurodevelopmental phenotypes. FAN1 encodes a DNA repair enzyme, thus implicating abnormalities in DNA repair in the susceptibility to SCZ or ASD. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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