Long-Standing Balancing Selection in the THBS4 Gene: Influence on Sex-Specific Brain Expression and Gray Matter Volumes in Alzheimer Disease
Cagliani, Rachele et al.
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| Format: | artículo biblioteca |
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John Wiley & Sons
2013-05
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| Subjects: | THBS4, Balancing selection, Brain, Alzheimer disease, Transcriptional regulation, |
| Online Access: | http://hdl.handle.net/10261/113684 |
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dig-ibe-es-10261-1136842016-02-17T19:54:33Z Long-Standing Balancing Selection in the THBS4 Gene: Influence on Sex-Specific Brain Expression and Gray Matter Volumes in Alzheimer Disease Cagliani, Rachele Sikora, Martin Casals, Ferran Sironi, Manuela THBS4 Balancing selection Brain Alzheimer disease Transcriptional regulation Cagliani, Rachele et al. The THBS4 gene encodes a glycoprotein involved in inflammatory responses and synaptogenesis. THBS4 is expressed at higher levels in the brain of humans compared with nonhuman primates, and the protein accumulates in β-amyloid plaques. We analyzed THBS4 genetic variability in humans and show that two haplotypes (hap1 and hap2) are maintained by balancing selection and modulate THBS4 expression in lymphocytes. Indeed, the balancing selection region covers a predicted transcriptional enhancer. In humans, but not in macaques and chimpanzees, THBS4 brain expression increases with age, and variants in the balancing selection region interact with sex in influencing THBS4 expression (pinteraction = 0.038), with hap1 homozygous females showing lowest expression. In Alzheimer disease (AD) patients, significant interactions between sex and THBS4 genotype were detected for peripheral gray matter (pinteraction = 0.014) and total gray matter (pinteraction = 0.012) volumes. Similarly to the gene expression results, the interaction is mainly mediated by hap1 homozygous AD females, who show reduced volumes. Thus, the balancing selection target in THBS4 is likely represented by one or more variants that regulate tissue-specific and sex-specific gene expression. The selection signature associated with THBS4 might not be related to AD pathogenesis, but rather to inflammatory responses. © 2013 Wiley Periodicals, Inc. Peer Reviewed 2015-04-15T10:08:14Z 2015-04-15T10:08:14Z 2013-05 2015-04-15T10:08:15Z artículo http://purl.org/coar/resource_type/c_6501 doi: 10.1002/humu.22301 issn: 1059-7794 e-issn: 1098-1004 Human Mutation 34(5): 743-753 (2013) http://hdl.handle.net/10261/113684 10.1002/humu.22301 http://dx.doi.org/10.1002/humu.22301 none John Wiley & Sons |
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THBS4 Balancing selection Brain Alzheimer disease Transcriptional regulation THBS4 Balancing selection Brain Alzheimer disease Transcriptional regulation |
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THBS4 Balancing selection Brain Alzheimer disease Transcriptional regulation THBS4 Balancing selection Brain Alzheimer disease Transcriptional regulation Cagliani, Rachele Sikora, Martin Casals, Ferran Sironi, Manuela Long-Standing Balancing Selection in the THBS4 Gene: Influence on Sex-Specific Brain Expression and Gray Matter Volumes in Alzheimer Disease |
| description |
Cagliani, Rachele et al. |
| format |
artículo |
| topic_facet |
THBS4 Balancing selection Brain Alzheimer disease Transcriptional regulation |
| author |
Cagliani, Rachele Sikora, Martin Casals, Ferran Sironi, Manuela |
| author_facet |
Cagliani, Rachele Sikora, Martin Casals, Ferran Sironi, Manuela |
| author_sort |
Cagliani, Rachele |
| title |
Long-Standing Balancing Selection in the THBS4 Gene: Influence on Sex-Specific Brain Expression and Gray Matter Volumes in Alzheimer Disease |
| title_short |
Long-Standing Balancing Selection in the THBS4 Gene: Influence on Sex-Specific Brain Expression and Gray Matter Volumes in Alzheimer Disease |
| title_full |
Long-Standing Balancing Selection in the THBS4 Gene: Influence on Sex-Specific Brain Expression and Gray Matter Volumes in Alzheimer Disease |
| title_fullStr |
Long-Standing Balancing Selection in the THBS4 Gene: Influence on Sex-Specific Brain Expression and Gray Matter Volumes in Alzheimer Disease |
| title_full_unstemmed |
Long-Standing Balancing Selection in the THBS4 Gene: Influence on Sex-Specific Brain Expression and Gray Matter Volumes in Alzheimer Disease |
| title_sort |
long-standing balancing selection in the thbs4 gene: influence on sex-specific brain expression and gray matter volumes in alzheimer disease |
| publisher |
John Wiley & Sons |
| publishDate |
2013-05 |
| url |
http://hdl.handle.net/10261/113684 |
| work_keys_str_mv |
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| _version_ |
1777668598259515392 |