Normal variants of Microcephalin and ASPM do not account for brain size variability

• Published in: Human molecular genetics 2006-06, Vol.15 (12), p.2025-2029
• Main Authors: Woods, Roger P., Freimer, Nelson B., De Young, Joseph A., Fears, Scott C., Sicotte, Nancy L., Service, Susan K., Valentino, Daniel J., Toga, Arthur W., Mazziotta, John C.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Biological and medical sciences; Brain - anatomy & histology; Fundamental and applied biological sciences. Psychology; Genetics of eukaryotes. Biological and molecular evolution; Genotype; Humans; Magnetic Resonance Imaging; Microcephaly - genetics; Molecular and cellular biology; Nerve Tissue Proteins - genetics; Organ Size; Polymerase Chain Reaction; Polymorphism, Single Nucleotide
• ISSN: 0964-6906; 1460-2083
• DOI: 10.1093/hmg/ddl126

Normal human brain volume is heritable. The genes responsible for variation in brain volume are not known. Microcephalin (MCPH1) and ASPM (abnormal spindle-like microcephaly associated) have been proposed as candidate genes as mutations in both genes are associated with microcephaly, and common variants of each gene are apparently under strong positive selective pressure. In 120 normal subjects, we genotyped these variants and measured brain volumes using magnetic resonance imaging. We found no evidence that the selected alleles were associated with increases or decreases in brain volume. This result suggests that the selective pressure on these genes may be related to subtle neurobiological effects or to their expression outside the brain.