NDLI: Left-Right Axis Differentiation and Functional Lateralization: a Haplotype in the Methyltransferase Encoding Gene SETDB2 Might Mediate Handedness in Healthy Adults

Content Provider	Springer Nature Link
Author	Ocklenburg, Sebastian Arning, Larissa Gerding, Wanda M. Hengstler, Jan G. Epplen, Jörg T. Güntürkün, Onur Beste, Christian Akkad, Denis A.
Copyright Year	2015
Abstract	Handedness is a multifactorial trait, and genes contributing to the differentiation of the left-right axis during embryogenesis have been identified as a major gene group associated with this trait. The methyltransferase SETDB2 (SET domain, bifurcated 2) has been shown to regulate structural left-right asymmetry in the vertebrate central nervous system by suppressing fgf8 expression. Here, we investigated the relation of genetic variation in SETDB2—and its paralogue SETDB1—with different handedness phenotypes in 950 healthy adult participants. We identified a haplotype on SETDB2 for which homozygous individuals showed a significantly lower lateralization quotient for handedness than the rest of the cohort after correction for multiple comparisons. Moreover, direction of handedness was significantly associated with genetic variation in this haplotype. This effect was mainly, but not exclusively, driven by the sequence variation rs4942830, as individuals homozygous for the A allele of this single nucleotide polymorphism had a significantly lower lateralization quotient than individuals with at least one T allele. These findings further confirm a role of genetic pathways relevant for structural left-right axis differentiation for functional lateralization. Moreover, as the protein encoded by SETDB2 regulates gene expression epigenetically by histone H3 methylation, our findings highlight the importance of investigating the role of epigenetic modulations of gene expression in relation to handedness.
Starting Page	6355
Ending Page	6361
Page Count	7
File Format	PDF
ISSN	08937648
Journal	Molecular Neurobiology
Volume Number	53
Issue Number	9
e-ISSN	15591182
Language	English
Publisher	Springer US
Publisher Date	2015-11-16
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Genetic association study SNP Laterality Lateralization Direction of lateralization Cerebral asymmetries Ontogenesis Neurosciences Neurobiology Cell Biology Neurology
Content Type	Text
Resource Type	Article
Subject	Neurology Cellular and Molecular Neuroscience

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