Sex-dependent association of common variants of microcephaly genes with brain structure.
Proc Natl Acad Sci U S A
; 107(1): 384-8, 2010 Jan 05.
Article
en En
| MEDLINE
| ID: mdl-20080800
ABSTRACT
Loss-of-function mutations in the genes associated with primary microcephaly (MCPH) reduce human brain size by about two-thirds, without producing gross abnormalities in brain organization or physiology and leaving other organs largely unaffected [Woods CG, et al. (2005) Am J Hum Genet 76717-728]. There is also evidence suggesting that MCPH genes have evolved rapidly in primates and humans and have been subjected to selection in recent human evolution [Vallender EJ, et al. (2008) Trends Neurosci 31637-644]. Here, we show that common variants of MCPH genes account for some of the common variation in brain structure in humans, independently of disease status. We investigated the correlations of SNPs from four MCPH genes with brain morphometry phenotypes obtained with MRI. We found significant, sex-specific associations between common, nonexonic, SNPs of the genes CDK5RAP2, MCPH1, and ASPM, with brain volume or cortical surface area in an ethnically homogenous Norwegian discovery sample (n = 287), including patients with mental illness. The most strongly associated SNP findings were replicated in an independent North American sample (n = 656), which included patients with dementia. These results are consistent with the view that common variation in brain structure is associated with genetic variants located in nonexonic, presumably regulatory, regions.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Encéfalo
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Polimorfismo de Nucleótido Simple
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Microcefalia
Tipo de estudio:
Risk_factors_studies
Límite:
Adult
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Animals
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Año:
2010
Tipo del documento:
Article
País de afiliación:
Noruega