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TY - JOUR AU - Bond, Jacquelyn AU - Roberts, Emma AU - Mochida, Ganesh H. AU - Hampshire, Daniel J. AU - Scott, Sheila AU - Askham, Jonathan M. AU - Springell, Kelly AU - Mahadevan, Meera AU - Crow, Yanick J. AU - Markham, Alexander F. AU - Walsh, Christopher A. AU - Woods, C. Geoffrey PY - 2002 DA - 2002/10/01 TI - ASPM is a major determinant of cerebral cortical size JO - Nature Genetics SP - 316 EP - 320 VL - 32 IS - 2 AB - One of the most notable trends in mammalian evolution is the massive increase in size of the cerebral cortex, especially in primates. Humans with autosomal recessive primary microcephaly (MCPH) show a small but otherwise grossly normal cerebral cortex associated with mild to moderate mental retardation1,2,3,4. Genes linked to this condition offer potential insights into the development and evolution of the cerebral cortex. Here we show that the most common cause of MCPH is homozygous mutation of ASPM, the human ortholog of the Drosophila melanogaster abnormal spindle gene (asp)5, which is essential for normal mitotic spindle function in embryonic neuroblasts6. The mouse gene Aspm is expressed specifically in the primary sites of prenatal cerebral cortical neurogenesis. Notably, the predicted ASPM proteins encode systematically larger numbers of repeated 'IQ' domains between flies, mice and humans, with the predominant difference between Aspm and ASPM being a single large insertion coding for IQ domains. Our results and evolutionary considerations suggest that brain size is controlled in part through modulation of mitotic spindle activity in neuronal progenitor cells. SN - 1546-1718 UR - https://doi.org/10.1038/ng995 DO - 10.1038/ng995 ID - Bond2002 ER -