DUF1220 domains, cognitive disease, and human brain evolution.
Cold Spring Harb Symp Quant Biol. 2009; 74: 375-82
Display abstract
We have established that human genome sequences encoding a novel protein domain, DUF1220, show a dramatically elevated copy number in the human lineage (>200copies in humans vs. 1 in mouse/rat) and may be important to human evolutionaryadaptation. Copy-number variations (CNVs) in the 1q21.1 region, where mostDUF1220 sequences map, have now been implicated in numerous diseases associatedwith cognitive dysfunction, including autism, autism spectrum disorder, mentalretardation, schizophrenia, microcephaly, and macrocephaly. We report here thatthese disease-related 1q21.1 CNVs either encompass or are directly flanked byDUF1220 sequences and exhibit a dosage-related correlation with human brain size.Microcephaly-producing 1q21.1 CNVs are deletions, whereas macrocephaly-producing 1q21.1 CNVs are duplications. Similarly, 1q21.1 deletions and smaller brain size are linked with schizophrenia, whereas 1q21.1 duplications and larger brain size are associated with autism. Interestingly, these two diseases are thought to bephenotypic opposites. These data suggest a model which proposes that (1) DUF1220 domain copy number may be involved in influencing human brain size and (2) theevolutionary advantage of rapidly increasing DUF1220 copy number in the humanlineage has resulted in favoring retention of the high genomic instability of the1q21.1 region, which, in turn, has precipitated a spectrum of recurrent humanbrain and developmental disorders.
Links (links to other resources describing this domain)
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