title: Investigation of MCPH1 G37995C and ASPM A44871G polymorphisms and brain size in a healthy cohort.
abstract: Loss-of-function mutations in MCPH1 and ASPM are responsible for some cases of autosomal recessive primary microcephaly. Recent studies have indicated that certain common variants of these genes have been positively selected for during the evolution of modern humans. It is therefore possible that these variants may predispose to an increase in brain size in the normal human population. We genotyped the MCPH1 G37995C and ASPM A44871G polymorphisms in a cohort of 118 healthy people who had undergone structural magnetic resonance imaging analysis. We did not detect significant association of either MCPH1 G37995C or ASPM A44871G genotype with whole brain volume, cerebral cortical volume or proportion of grey matter in this cohort. Nor did we detect an association of combined MCPH1 37995C and ASPM 44871G allele dosage with these brain measurements. These results were also confirmed in an age-restricted subcohort of 94 individuals. This study suggests that phenotypes other than brain size may have been selected for in ASPM and MCPH1 variants during evolution of modern humans.
authors.affiliation: Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia.
authors.forename: C
authors.initials: C
authors.lastname: Dobson-Stone
authors.forename: J M
authors.initials: JM
authors.lastname: Gatt
authors.forename: S A
authors.initials: SA
authors.lastname: Kuan
authors.forename: S M
authors.initials: SM
authors.lastname: Grieve
authors.forename: E
authors.initials: E
authors.lastname: Gordon
authors.forename: L M
authors.initials: LM
authors.lastname: Williams
authors.forename: P R
authors.initials: PR
authors.lastname: Schofield
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D005075:Biological Evolution; D001921:Brain / Q000033:anatomy & histology*; D018797:Cell Cycle Proteins; D002648:Child; D003598:Cytoskeletal Proteins; D005260:Female; D005838:Genotype; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008831:Microcephaly; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009929:Organ Size / Q000235:genetics; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic
chemical_list: C467202:ASPM protein, human; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; C460645:MCPH1 protein, human; D009419:Nerve Tissue Proteins