The Experts below are selected from a list of 75 Experts worldwide ranked by ideXlab platform

Nilufer Ertekintaner - One of the best experts on this subject based on the ideXlab platform.

  • genetic variation in PCDH11X is associated with susceptibility to late onset alzheimer s disease
    Nature Genetics, 2009
    Co-Authors: Minerva M Carrasquillo, Fanggeng Zou, Shane V Pankratz, Samantha L Wilcox, Louise P Walker, Samuel Younkin, Curtis S Younkin, Linda H Younkin, Gina Bisceglio, Nilufer Ertekintaner
    Abstract:

    Steve Younkin and colleagues report the results of a genome-wide association study for late-onset Alzheimer's disease. A variant on the X chromosome in PCDH11X is associated with increased risk of the disorder. PCDH11X encodes a protocadherin and is a member of a cell surface receptor molecule family. By analyzing late-onset Alzheimer's disease (LOAD) in a genome-wide association study (313,504 SNPs, three series, 844 cases and 1,255 controls) and evaluating the 25 SNPs with the most significant allelic association in four additional series (1,547 cases and 1,209 controls), we identified a SNP (rs5984894) on Xq21.3 in PCDH11X that is strongly associated with LOAD in individuals of European descent from the United States. Analysis of rs5984894 by multivariable logistic regression adjusted for sex gave global P values of 5.7 × 10−5 in stage 1, 4.8 × 10−6 in stage 2 and 3.9 × 10−12 in the combined data. Odds ratios were 1.75 (95% CI = 1.42–2.16) for female homozygotes (P = 2.0 × 10−7) and 1.26 (95% CI = 1.05–1.51) for female heterozygotes (P = 0.01) compared to female noncarriers. For male hemizygotes (P = 0.07) compared to male noncarriers, the odds ratio was 1.18 (95% CI = 0.99–1.41).

Timothy J Crow - One of the best experts on this subject based on the ideXlab platform.

  • the protocadherin 11x y PCDH11X y gene pair as determinant of cerebral asymmetry in modern homo sapiens
    Annals of the New York Academy of Sciences, 2013
    Co-Authors: T H Priddle, Timothy J Crow
    Abstract:

    Annett's right-shift theory proposes that human cerebral dominance (the functional and anatomical asymmetry or torque along the antero-posterior axis) and handedness are determined by a single “right-shift” gene. Familial transmission of handedness and specific deviations of cerebral dominance in sex chromosome aneuploidies implicate a locus within an X–Y homologous region of the sex chromosomes. The Xq21.3/Yp11.2 human-specific region of homology includes the protocadherin 11X/Y (PCDH11X/Y) gene pair, which encode cell adhesion molecules subject to accelerated evolution following the separation of the human and chimpanzee lineages six million years ago. PCDH11X and PCDH11Y, differentially regulated by retinoic acid, are highly expressed in the ventricular zone, subplate, and cortical plate of the developing cerebral cortex. Both proteins interact with β-catenin, a protein that plays a role in determining axis formation and regulating cortical size. In this way, the PCDH11X/Y gene pair determines cerebral asymmetry by initiating the right shift in Homo sapiens.

  • inactivation status of PCDH11X sexual dimorphisms in gene expression levels in brain
    Human Genetics, 2006
    Co-Authors: Alexandra M Lopes, James Close, Norman L J Ross, Adam Dagnall, A Amorim, Timothy J Crow
    Abstract:

    Genes escaping X-inactivation are predicted to contribute to differences in gene dosage between the sexes and are the prime candidates for being involved in the phenotype observed in individuals with X chromosome aneuploidies. Of particular interest is ProtocadherinX (PCDH11X or PCDHX), a recently described gene expressed in brain. In humans, PCDH11X has a homologue on the Y chromosome and is predicted to escape from X-inactivation. Employing bisulphite sequencing analysis we found absence of CpG island methylation on both the active and the inactive X chromosomes, providing a strong indication that PCDH11X escapes inactivation in humans. Furthermore, a sexual dimorphism in levels of expression in brain tissue was observed by quantitative real-time PCR, with females presenting an up to 2-fold excess in the abundance of PCDH11X transcripts. We relate these findings to sexually dimorphic traits in the human brain. Interestingly, PCDH11X/Y gene pair is unique to Homo sapiens, since the X-linked gene was transposed to the Y chromosome after the human-chimpanzee lineages split. Although no differences in promoter methylation were found between humans and chimpanzees, evidence of an upregulation of PCDH11X in humans deserves further investigation.

Eliecer Coto - One of the best experts on this subject based on the ideXlab platform.

  • lack of association between protocadherin 11 x y PCDH11X and pcdh11y polymorphisms and late onset alzheimer s disease
    Brain Research, 2011
    Co-Authors: Ana Miar, Victoria Alvarez, Ana I Corao, Belen Alonso, Marta Diaz, Manuel Menendez, Carmen Martinez, Maite Calatayud, German Moris, Eliecer Coto
    Abstract:

    A recent genome-wide association study (GWA) reported a significant association between single nucleotide polymorphisms (SNPs) at the PCDH11X gene and late-onset Alzheimer's disease (LOAD). Our research was designated to replicate this association, including non previously analyzed PCDH11X and PCDH11Y SNPs. We genotyped four PCDH11X and one PCDH11Y SNPs in a total of 420 LOAD patients and 350 healthy controls from Spain. Allele and genotype frequencies did not differ between patients and controls for the five SNPs, even after correcting by gender, age, and APOE-e4 status. Our data were in agreement with recent reports that failed to confirm the association between PCDH11X polymorphisms and LOAD, and extended the lack of association to common PCDH11Y variants.

Margaret A Pericakvance - One of the best experts on this subject based on the ideXlab platform.

Peng Zhang - One of the best experts on this subject based on the ideXlab platform.

  • effects of PCDH11X on the development of cortical neuronal dendritic branching
    Chin J Neurotrauma Surg(Electronic Edition), 2016
    Co-Authors: Peng Zhang, Lijun Niu, Qingxia Tao, Ning Liu, Chong Wang
    Abstract:

    Objective To discuss the effects of Protocadherin 11 X-linked protein (PCDH11X) on formation of neuronal dendritic branching. Methods In this study, using gain-of-function and loss-of-function studies, we count the number of neural dendritic branching, and analyzed the data with SPSS 13.0 software by one way ANOVA. Results Compared with the control GFP vector, PCDH11X-shRNA increased, whereas pCAG-PCDH11X-GFP decreased the number of primary and secondary dendrites. The number of dendritic tips was reduced in neurons overexpressing pCAG-PCDH11X-GFP, whereas it was increased when PCDH11X activity was inhibited by overexpression of PCDH11X-shRNA. The effects of PCDH11X-shRNA and pCAG-PCDH11X-GFP on dendritic branching were confirmed by Sholl analysis. Therefore PCDH11X acts as a negtive regulator of dendritic branching in cultured cortical neurons from embryonic day 16 mouse embryos. Conclusions PCDH11X Negatively Regulates Dendritic Branching, including primary dendrites, secondary dendrites, dendritic tips and crossing number. Key words: PCDH11X; Central nervous system; Dendritic branching

  • PCDH11X negatively regulates dendritic branching
    Journal of Molecular Neuroscience, 2015
    Co-Authors: Lijun Niu, Ning Liu, Chong Wang, Zhongjie Yan, Yiwu Dai, Peng Zhang
    Abstract:

    Proper formation of neuronal dendritic branching is crucial for correct brain function. The number and distribution of receptive synaptic contacts are defined by the size and shape of dendritic arbors. Our previous research found that protocadherin 11 X-linked protein (PCDH11X) is predominantly expressed in neurons and has an influence on dendritic branching. In this study, gain-of-function and loss-of-function experiments revealed that PCDH11X acts as a negative regulator of dendritic branching in cultured cortical neurons derived from embryonic day 16 mice. Overexpression of wild-type PCDH11X (PCDH11X-GFP) reduced dendritic complexity, whereas knockdown of PCDH11X increased dendritic branching. It was further demonstrated that PCDH11X activates PI3K/AKT signaling to negatively regulate dendritic branching.