Human core duplicon gene families: game changers or game players?

Bekpen, Cemalettin; Tautz, Diethard

Despite its broad expression, the functional analysis of this gene family has focused on brain-and/or neuron-specific functions. This was triggered by the observation that the 1q21.1 chromosome region in humans, which is associated with brain disorders such as micro-or macrocephaly, autism and schizophrenia, includes a number of the NPBPF1 genes [25] . Further, a correlation was found between Olduvai copy number and brain size in humans. This correlation was most prominent in affected patients, but copy number was also associated with gray-matter volume in healthy controls [26] . Over-expression of Olduvai sequences in neural stem cells promotes proliferation [27] [28] [29] . Further studies also suggested a correlation between Olduvai copy number and schizophrenia risk and severity [30] as well as with IQ and total mathematical aptitude scores [31] , although the breadth of this latter study is limited. While these results suggest a particularly interesting function of NBPF genes in human brain evolution with implications for the etiology of brain diseases [21] , more studies are required to support this notion. Notably, copy number variations (CNVs) and deletions in the 1q21.1 region are also correlated with heart [32, 33] and kidney [34] diseases. Given that NBPF11 genes are broadly expressed, they could have a more general function.