Por favor, use este identificador para citar o enlazar a este item:
http://hdl.handle.net/10261/113684COMPARTIR / EXPORTAR:
 SHARE
 CORE
BASE
|
|
| Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE | |
| Título: | Long-Standing Balancing Selection in the THBS4 Gene: Influence on Sex-Specific Brain Expression and Gray Matter Volumes in Alzheimer Disease |
Autor: | Cagliani, Rachele; Sikora, Martin CSIC ORCID; Casals, Ferran CSIC ORCID; Sironi, Manuela | Palabras clave: | THBS4 Balancing selection Brain Alzheimer disease Transcriptional regulation |
Fecha de publicación: | may-2013 | Editor: | John Wiley & Sons | Citación: | Human Mutation 34(5): 743-753 (2013) | Resumen: | 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. | Descripción: | Cagliani, Rachele et al. | Versión del editor: | http://dx.doi.org/10.1002/humu.22301 | URI: | http://hdl.handle.net/10261/113684 | DOI: | 10.1002/humu.22301 | Identificadores: | doi: 10.1002/humu.22301 issn: 1059-7794 e-issn: 1098-1004 |
| Aparece en las colecciones: | (IBE) Artículos |
Ficheros en este ítem:
| Fichero | Descripción | Tamaño | Formato | |
|---|---|---|---|---|
| accesoRestringido.pdf | 15,38 kB | Adobe PDF |  Visualizar/Abrir |
CORE Recommender
SCOPUSTM
Citations
7
checked on 16-abr-2024
WEB OF SCIENCETM
Citations
8
checked on 15-feb-2024
Page view(s)
289
checked on 22-abr-2024
Download(s)
148
checked on 22-abr-2024
Google ScholarTM
Check
Altmetric
Altmetric
NOTA: Los ítems de Digital.CSIC están protegidos por copyright, con todos los derechos reservados, a menos que se indique lo contrario.