31 research outputs found
X chromosome inactivation in female predisposition to autoimmunity
Ankara : The Department of Molecular Biology and Genetics and the Institute of Engineering and Science of Bilkent University, 2008.Thesis (Ph.D.] -- Bilkent University, 2008.Includes bibliographical references leaves 95-121.The high female preponderance is thought to be important in identifying the
etiological factors. Sex hormones, pregnancy related microchimerism, and
environmental factors are investigated as likely candidates. Disturbed Xchromosome
inactivation (XCI) is another candidate, which may contribute to the
break-down of self-tolerance. In this study, we tested the hypothesis that “loss of
mosaicism” for X-linked gene expression may contribute to autoimmune disease
etiology. Therefore, XCI status of healthy individuals and patients diagnosed with
scleroderma (SSc), autoimmune thyroiditis (AITDs), Sjogren’s syndrome
(SICCA), and juvenile idiopathic arthritis (JIA) in the Turkish population were
analyzed by genotyping the methylation status of a CAG polymorphism in the
androgen receptor (AR) gene. Extremely skewed XCI was observed in a significant
proportion of SSc (OR: 38.9; P<0.0001), AITDs (OR: 9.6; P<0.0001), and JIA
(OR: 4.4; P=0.0022). Further genotyping of AITDs in Tunisian and SSc in the US
population supported the initial observations (OR: 3.8; P=0.0046; OR: 3.8;
P<0.0001) respectively. Analysis of rheumatoid arthritis (RA) in the Tunisian
population suggests that extremely skewed XCI (OR: 6.7; P<0.0001) could be
involved in disease pathogenesis. Moreover, pre-eclampsia, a disease in which
autoimmunity may be important, skewed XCI was observed (OR; 11.7; P=0.0005).
However, in SICCA random patterns of XCI was observed suggesting that extreme
skewing is not a common feature of all female prevalent autoimmune disorders. In
conclusion, our results suggest that extremely skewed XCI may be important
factor in autoimmune disease pathogenesis.Uz, ElifPh.D
Analyzing the soil texture effect on promoting water holding capacity by polyacrylamide
Polyacrylamide (PAM) has been widely used to improve soil water holding capacity and control infiltration rate
of the soils. However, limited studies have been conducted on the interactions between soil water holding
capacity and PAM rates in different soil textures. This study targeted to analyze the relations between soil
texture and water holding capacity as a response of increasing PAM applications rate. PAM rates of 0.03, 0.1,
0.13, 0.16, 0.23, 0.33 and 0.67% by weight were applied to clay loam, clay and sandy loam soils. Water holding
capacity (q) at field capacity (q 0.01 MPa for sandy loam and q0.033MPa for clay loam and clay) and wilting point
(q1.50 MPa) were measured with a pressure plate apparatus. The values of water holding capacity were regressed
as a function of PAM rate, and the slope and intercepts of regression lines for clay loam, clay and sandy loam
soils were compared to decide the homogeneity of these functions. Increasing PAM rate significantly increased
the water holding capacity in all three soils (P<0.05). The regression lines obtained for sandy loam, clay loam,
and clay were all significantly different from one to another, revealing that soil texture has a significant effect on
the function of PAM in promoting water holding capacity in these soils. Therefore, we concluded that soil
texture should be considered in optimizing the results from PAM applications
Skewed X-chromosome inactivation in scleroderma.
Scleroderma is a female-prevalent autoimmune disease of unclear etiology. Two fundamental gender differences, skewed X-chromosome inactivation (XCI) and pregnancy-related microchimerism, have been implicated in scleroderma. We investigated the XCI patterns of female scleroderma patients and the parental origin of the inactive X chromosome in those patients having skewed XCI patterns (>80%). In addition, we investigated whether a correlation exists between XCI patterns and microchimerism in a well-characterized cohort. About 195 female scleroderma patients and 160 female controls were analyzed for the androgen receptor locus to assess XCI patterns in the DNA extracted from peripheral blood cells. Skewed XCI was observed in 67 (44.9%) of 149 informative patients and in 10 of 124 healthy controls (8.0%) [odds ratio (OR) = 9.3 (95% confidence interval (CI) 4.3-20.6, P 90%) was present in 44 of 149 patients (29.5%) but only in 3 of 124 controls (2.4%; OR = 16.9; 95% CI 4.8-70.4, P < 0.0001). Parental origin of the inactive X chromosome was investigated for ten patients for whom maternal DNA was informative, and the inactive X chromosome was of maternal origin in eight patients and of paternal origin in two patients. Skewed XCI mosaicism could be considered as an important risk factor in scleroderma
Analysis of skewed X-chromosome inactivation in females with rheumatoid arthritis and autoimmune thyroid diseases
Introduction: The majority of autoimmune diseases such as rheumatoid arthritis (RA) and autoimmune thyroid diseases (AITDs) are characterized by a striking female predominance superimposed on a predisposing genetic background. The role of extremely skewed X-chromosome inactivation (XCI) has been questioned in the pathogenesis of several autoimmune diseases. Methods: We examined XCI profiles of females affected with RA (n = 106), AITDs (n = 145) and age-matched healthy women (n = 257). XCI analysis was performed by enzymatic digestion of DNA with a methylation sensitive enzyme (HpaII) followed by PCR of a polymorphic CAG repeat in the androgen receptor (AR) gene. The XCI pattern was classified as skewed when 80% or more of the cells preferentially inactivated the same X-chromosome. Results: Skewed XCI was observed in 26 of the 76 informative RA patients (34.2%), 26 of the 100 informative AITDs patients (26%), and 19 of the 170 informative controls (11.2%) (P 90% inactivation of one allele, was present in 17 RA patients (22.4%), 14 AITDs patients (14.0%), and in only seven controls (4.1%, P 0.05). Conclusions: These results suggest a possible role for XCI mosaicism in the pathogenesis of RA and AITDs and may in part explain the female preponderance of these diseases. © 2009 Chabchoub et al.; licensee BioMed Central Ltd
Extreme Clonality in Lymphoblastoid Cell Lines with Implications for Allele Specific Expression Analyses
Lymphoblastoid cell lines (LCL) are being actively and extensively used to examine the expression of specific genes and genome-wide expression profiles, including allele specific expression assays. However, it has recently been shown that approximately 10% of human genes exhibit random patterns of monoallelic expression within single clones of LCLs. Consequently allelic imbalance studies could be significantly compromised if bulk populations of donor cells are clonal, or near clonal. Here, using X chromosome inactivation as a readout, we confirm and quantify widespread near monoclonality in two independent sets of cell lines. Consequently, we recommend where possible the use of bulk, non cell line, ex vivo cells for allele specific expression assays
Analysis of triticum monococcum ssp, boeoticum accessions distributed over Turkey using aflp markers and assesment of polymorphism levels of newly isolated ssr markers.
TMCO1 Gen Sekans Varyanlatlarının Fonksiyonel Özelliklerinin In Silico Analizlerlerle Değerlendirilmesi
Transmembrane
and Coiled-Coil Domains 1 (TMCO1) protein is encoded by TMCO1 gene consists of 7 exons. Previous studies have identified
multiple TMCO1 variants in patients
with cerebro-facio-thoracic dysplasia (CFTD) and TMCO1 locus was also shown to be associated with primary open angle
glaucoma (POAG). However, there are limited number of research exist reporting
associations of the TMCO1 gene
sequence variants and majority of the findings affirm the pathogenicity of the
nonsense and frameshift TMCO1 variants
and their associations with clinical phenotypes. Thus functional properties of
the single nucleotide variants causing amino acid changes in the TMCO1 are yet
to be comprehensively elucidated. In this study, we evaluated the effects of
amino acid substitutions on protein structure, identified their putative roles
in post-translational modifications (PTM) and in regulatory mechanism for TMCO1
protein. We classified 41 missense variants as pathogenic based on combined
scores of common in silico tools (SIFT, MutationTaster2, Polyphen2). Of these
41 variants, four (p.K211Q, p.K105E, p.S235F, p.K237R) were identified to be
located in PTMs and regulatory protein binding sites; thus they were proposed
to be putative functional variants. Moreover, rs1387528611 (p.Lys128Gln) had
also strong evidence (RegulomeDB score=2b) for its possible regulatory
function. The results of our in silico analyses highlight the functional
importance of the missense TMCO1
variants that may contribute to the TMCO1-associated
disease phenotypes and further in vivo evaluation yet to be needed to uncover
their role in human diseases