File this story under “the more you know, the more you don’t know” or simply under “WTF!” The new paper, “Microduplications of 16p11.2 are associated with schizophrenia” [doi:10.1038/ng.474] reveals that a short stretch of DNA on chromosome 16p11.2 is – very rarely – duplicated and – more rarely – deleted. In an analysis of 8,590 individuals with schizophrenia, 2,172 with developmental delay or autism, 4,822 with bipolar disorder and 30,492 controls, the the microduplication of 16p11.2 was strongly associated with schizophrenia, bipolar and autism while the reciprocal microdeletion was strongly associated with developmental delay or autism – but not associated with schizophrenia or bipolar disorder.
OK, so the title of my post is misleading (hey, its a blog) since there are clearly many additional factors that contribute to the developmental outcome of autism vs. schizophrenia, but this stretch of DNA seems to hold clues about early development of brain systems that go awry in both disorders. Here is a list of the brain expressed genes in this 600 kbp region (in order from telomere-side to centromere-side): SPN, QPRT, C16orf54, MAZ, PRRT2, C16orf53, MVP, CDIPT, SEZ6L2, ASPHD1, KCTD13, TMEM219, TAOK2, HIRIP3, INO80E, DOC2A, FLJ25404, FAM57B, ALDOA, PPP4C, TBX6, YPEL3, GDPD3, MAPK3, CORO1A.
Any guess as to which one(s) are the culprits? I’ll go with HIRIP3 given its role in chromatin structure regulation – and the consequent regulation of under- (schiz?)/over- (autism) growth of synapses. What an amazing mystery to pursue.
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