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X Chromosome Inactivation (x + chromosome_inactivation)

Distribution by Scientific Domains

Medical Sciences	50%
Life Sciences	50%

Selected Abstracts

SEXUAL ANTAGONISM AND THE EVOLUTION OF X CHROMOSOME INACTIVATION

EVOLUTION, Issue 8 2008
Jan Engelstädter
In most female mammals, one of the two X chromosomes is inactivated early in embryogenesis. Expression of most genes on this chromosome is shut down, and the inactive state is maintained throughout life in all somatic cells. It is generally believed that X-inactivation evolved as a means of achieving equal gene expression in males and females (dosage compensation). Following degeneration of genes on the Y chromosome, gene expression on X chromosomes in males and females is upregulated. This results in closer to optimal gene expression in males, but deleterious overexpression in females. In response, selection is proposed to favor inactivation of one of the X chromosomes in females, restoring optimal gene expression. Here, we make a first attempt at shedding light on this intricate process from a population genetic perspective, elucidating the sexually antagonistic selective forces involved. We derive conditions for the process to work and analyze evolutionary stability of the system. The implications of our results are discussed in the light of empirical findings and a recently proposed alternative hypothesis for the evolution of X-inactivation. [source]

Mobile DNA elements in primate and human evolution

AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY, Issue S45 2007
Jinchuan Xing
Abstract Roughly 50% of the primate genome consists of mobile, repetitive DNA sequences such as Alu and LINE1 elements. The causes and evolutionary consequences of mobile element insertion, which have received considerable attention during the past decade, are reviewed in this article. Because of their unique mutational mechanisms, these elements are highly useful for answering phylogenetic questions. We demonstrate how they have been used to help resolve a number of questions in primate phylogeny, including the human,chimpanzee,gorilla trichotomy and New World primate phylogeny. Alu and LINE1 element insertion polymorphisms have also been analyzed in human populations to test hypotheses about human evolution and population affinities and to address forensic issues. Finally, these elements have had impacts on the genome itself. We review how they have influenced fundamental ongoing processes like nonhomologous recombination, genomic deletion, and X chromosome inactivation. Yrbk Phys Anthropol 50:2,19, 2007. © 2007 Wiley-Liss, Inc. [source]

Increased frequency of extremely skewed X chromosome inactivation in juvenile idiopathic arthritis

ARTHRITIS & RHEUMATISM, Issue 11 2009
Elif Uz
Objective Juvenile idiopathic arthritis (JIA) is a childhood rheumatic disease of unknown etiology. Two subgroups of JIA, i.e., oligoarticular and polyarticular, are thought to have an autoimmune component, and show a higher female:male ratio. Skewed X chromosome inactivation (XCI) has previously been shown to be associated with scleroderma and autoimmune thyroiditis, 2 autoimmune disorders occurring predominantly in females. This study was undertaken to extend the analysis to the pediatric age group and to determine the XCI profiles of patients with JIA. Methods A polymorphic repeat in the androgen receptor gene was genotyped to determine XCI status in 81 female patients with JIA (21 with polyarticular disease and 60 with oligoarticular disease) and 211 healthy female controls. DNA obtained from venous blood samples was used for this analysis. Results Informative data were obtained on 62 JIA patients and 155 controls. Skewed XCI was observed in 14 patients (22.6%) and 11 controls (7.1%) (P = 0.0036), and extreme skewing was apparent in 8 patients (12.9%) and 2 controls (1.3%) (P = 0.0008). Conclusion Our findings in the present study indicate that skewed XCI may be a risk factor for the occurrence of autoimmune disorders, including JIA. [source]

Silence of the fathers: Early X inactivation

BIOESSAYS, Issue 8 2004
Mimi K. Cheng
X chromosome inactivation is the mammalian answer to the dilemma of dosage compensation between males and females. The study of this fascinating form of chromosome-wide gene regulation has yielded surprising insights into early development and cellular memory. In the past few months, three papers1,3 reported unexpected findings about the paternal X chromosome (Xp). All three studies agree that the Xp is imprinted to become inactive earlier than ever suspected during embryonic development. Although apparently incomplete, this early form of inactivation insures dosage compensation throughout development. Silencing of the Xp persists in cells of extraembryonic tissues, but it is erased and followed by random X inactivation in cells of the embryo proper. These findings challenge several aspects of the current view of X inactivation during early development and may have profound impact on studies of pluripotency and epigenetics. BioEssays 26:821,824, 2004. © 2004 Wiley Periodicals, Inc. [source]

Precise microdissection of human bladder carcinomas reveals divergent tumor subclones in the same tumor

CANCER, Issue 1 2002
Liang Cheng M.D.
Abstract BACKGROUND Human bladder carcinoma is thought to arise from a field change that affects the entire urothelium. Whether independently transformed urothelial cell populations exist in the same patient is uncertain. METHODS We studied the clonality of urinary bladder carcinoma in 18 female patients who underwent cystectomy for urothelial carcinoma. None had multiple tumors. Tumor samples were obtained from different areas of the same tumor. Sixty-seven tumor samples were analyzed. Tumor genomic DNA was microdissected and extracted from formalin-fixed, paraffin-embedded slides. The clonality of urothelial tumors was evaluated on the basis of a polymorphism of the X chromosome-linked human androgen receptor gene (HUMARA) locus. The technique is dependent on digestion of DNA with the methylation-sensitive restriction enzyme HhaI, polymerase chain reaction (PCR) amplification of HUMARA locus, and detection of methylation of this locus. With this method, only the methylated HUMARA allele is selectively amplified by PCR. RESULTS Eleven of 18 patients were informative. Nonrandom inactivation of the X chromosome was found in 9 of the 11 informative patients (82%). Seven patients showed different patterns of nonrandom X chromosome inactivation for tumor samples obtained from different regions of the same tumor. Two patients showed the same pattern of nonrandom X chromosome inactivation in all samples. CONCLUSIONS Some muscle-invasive urothelial carcinomas may arise from independently transformed progenitor urothelial cells, supporting the "field effect" theory for bladder carcinogenesis. Cancer 2002;94:104,10. © 2002 American Cancer Society. [source]