• Mutation
  • Once the total outcomes of the two molecular analyses had been mixed, 28.6% from the cases were discordant in X-chromosome inactivation design and/or mutation, recommending multicentric origin. (immune-source.com)
  • mutation, clonal evaluation, HUMARA, intraglandular metastasis, multicentric incident, multiple papillary thyroid carcinoma, X-chromosome inactivation design Launch Papillary thyroid carcinoma (PTC) may be the most typical thyroid carcinoma, accounting for about 90% of all thyroid malignancies 1C3. (immune-source.com)
  • Mutation and imprinting of the XIST gene, a part of the X inactivation centre, can result in skewing. (wikipedia.org)
  • People carrying a mutation (abnormality) in this gene are at an increased risk of breast or ovarian cancer. (cancerindex.org)
  • Sp1 is a transcription factor that binds GC-rich consensus sequences, and mutation of the SRY binding sites leads to a 90% reduction in gene transcription. (wikipedia.org)
  • Mutation of the Zinc fingers or inactivation of WT1 results in reduced male gonad size. (wikipedia.org)
  • The androgen receptor (AR), which is defective due to a mutation in most of these syndromes, is a type of nuclear receptor that is activated by binding to either of the androgenic hormones (testosterone or dihydrotestosterone) in the cytoplasm, and then translocates into the nucleus where it binds to DNA, provided androgen response elements and coactivators are present. (wikipedia.org)
  • In this case, should a cell sustain only one mutation in the other RB gene, all Rb in that cell would be ineffective at inhibiting cell cycle progression, allowing cells to divide uncontrollably and eventually become cancerous. (wikipedia.org)
  • Less common are SRY-negative XX males which can be caused by a mutation in an autosomal or X chromosomal gene. (wikipedia.org)
  • Cytogenetic studies localized the region to the long arm of chromosome 13, and molecular genetic studies demonstrated that tumorigenesis was associated with chromosomal mechanisms, such as mitotic recombination or non-disjunction, that could lead to homozygosity of the mutation. (wikipedia.org)
  • Clonality
  • Molecular techniques to diagnose hematological malignancies based on the detection of clonality have been with us since the mid-1980s, based on the seminal observation that lymphoid cells rearrange their antigen receptor genes and that recurrent genetic rearrangements are present in myeloid neoplasms. (springer.com)
  • T-cell clonality determination using polymerase chain reaction (PCR) amplification of the T-cell receptor gamma-chain gene and capillary electrophoresis of fluorescently labeled PCR products. (springer.com)
  • genetic
  • In this study, molecular analysis of microsatellite alterations and X-chromosome inactivation status in separate urothelial carcinomas from the same patient was used to assess the molecular genetic relationships among the multiple coexisting tumors. (aacrjournals.org)
  • It is unknown whether a similar gene plays a role in human X inactivation, although a 2008 study found that skewing in humans is mostly caused by secondary events rather than a genetic tendency. (wikipedia.org)
  • Androgen insensitivity syndrome (AIS) is an intersex condition in which there is a partial or complete inability of many cells in the affected genetic male to respond to androgenic hormones. (wikipedia.org)
  • For an individual cell or lineage the inactivation is therefore skewed or 'non-random', and this can give rise to mild symptoms in female 'carriers' of X-linked genetic disorders. (wikipedia.org)
  • XX males that are SRY-positive have two X chromosomes, with one of them containing genetic material from the Y chromosome, making them phenotypically male but genetically female. (wikipedia.org)
  • Males with certain sex chromosome genetic conditions, such as Klinefelter's syndrome, will have a higher level of estradiol. (wikipedia.org)
  • clonal
  • Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: report of the BIOMED-2 Concerted Action BMH4-CT98-3936. (springer.com)
  • Thanks to these qualities of HUMARA gene, clonal origin of any tissue from a female mammalian organism can be determined. (wikipedia.org)
  • Two of three evaluable cases had a monoclonal pattern of inactivation, and the third case had a clonal expansion of cells with an altered microsatellite repeat sequence. (nih.gov)
  • LOH and X-chromosome inactivation assays show that the coexisting tumors in many cases of multifocal urothelial carcinoma have a unique clonal origin and arise from independently transformed progenitor urothelial cells, supporting the "field effect" theory for urothelial carcinogenesis. (aacrjournals.org)
  • exhibited that a distinct allele of the X-chromosome was inactivated in different tumor foci in three out of eight cases with multifocal PTC, suggesting independent clonal origins of these foci 13. (immune-source.com)
  • HUMARA
  • HUMARA gene, in particular, has three important features that make it highly convenient for the purpose. (wikipedia.org)
  • 3-) DNA is cleaned and the certain region of HUMARA gene is amplified by PCR using "suitable" primers (as an example, please see:Ref.2) 4-) After running PCR products through a gel, the gel is visualized and the results are analyzed accordingly. (wikipedia.org)
  • Table 1 Reported concordance of X-chromosome inactivation patterns in multifocal papillary thyroid carcinoma by HUMARA Although many investigators in the field of thyroid pathology are interested in Dovitinib Dilactic acid the pathogenesis of multifocal PTCs, the principal mechanism responsible for multifocal PTCs must still be decided. (immune-source.com)
  • polymorphism
  • These data established a functional polymorphism in type I IFN pathway gene TLR7 predisposing to SLE, especially in Chinese and Japanese male subjects. (pnas.org)
  • By using a candidate gene approach, we report herein that a functional polymorphism in 3′UTR of TLR7 is associated with SLE in Chinese and Japanese populations, with a stronger effect in male than female subjects. (pnas.org)
  • We investigated the association between polymorphism in the androgen receptor ( AR ) and vitamin D receptor ( VDR ) genes and breast cancer risk in a large population-based case-control study of genetically homogenous Swedish women. (aacrjournals.org)
  • transcription
  • This combination functions as a transcription complex to turn on androgen gene expression. (wikipedia.org)
  • MECP2, MBD1 and MBD2 can also repress transcription from methylated gene promoters. (wikipedia.org)
  • Cyclin D1-CDK4 inhibits pRb through phosphorylation, allowing E2F transcription factors to transcribe genes required for entry into the S phase. (wikipedia.org)
  • protein encoded
  • The protein encoded by this gene belongs to the highly conserved cyclin family, whose members are characterized by a dramatic periodicity in protein abundance throughout the cell cycle. (wikipedia.org)
  • The protein encoded by this gene is a phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase. (wikipedia.org)
  • The dickkopf protein encoded by DKK1 is an antagonistic inhibitor of the WNT signaling pathway that acts by isolating the LRP6 co-receptor so that it cannot aid in activating the WNT signaling pathway. (wikipedia.org)
  • molecular
  • Here we report the clinical and molecular characterization of two Xp11.22 deletions including SHROOM4 and CLCN5 genes. (biomedcentral.com)
  • Here we report the first clinical description and molecular characterization using array-CGH of a patient presenting two maternally inherited interstitial deletions of Xp11.22 in the same chromosome associated with severe psychomotor retardation and Dent disease. (biomedcentral.com)
  • phenotypes
  • Although translocated X chromosome segment in Yaa may contain as many as 16 genes, the major gene for causation of the autoimmune phenotypes was identified to be TLR7 ( 7 ), making it a potential susceptibility gene for SLE. (pnas.org)
  • mutant mice, which develop prostatic intraepithelial neoplasia and adenocarcinoma as a consequence of aging, as well as androgen-independent phenotypes following castration. (aacrjournals.org)
  • mutant mice are capable of surviving and proliferating in the absence of androgens and that they develop androgen-independent phenotypes well before they display overt prostatic intraepithelial neoplasia or cancer phenotypes. (aacrjournals.org)
  • We find that these mice can acquire androgen-independent phenotypes before the formation of overt PIN or cancer. (aacrjournals.org)
  • dihydrotestosterone
  • All aspects of prostate development and prostate carcinogenesis are critically dependent on the activity of the androgen receptor and its primary ligands, testosterone and dihydrotestosterone ( 1 - 7 ). (aacrjournals.org)
  • In contrast, the other endogenous androgens dihydrotestosterone (DHT) and androstenedione show low affinity for the receptor with less than 1% of that of testosterone, although DHT is still effective in activating the receptor at sufficiently high concentrations. (wikipedia.org)
  • Thus
  • 5 CTCF was shown to be involved in X chromosome counting, the first step of XCI, along with non-coding RNA Jpx , and thus haploinsufficiency of CTCF would result in aberrant XCI. (bmj.com)
  • Thus, when DNA from a healthy female tissue is amplified by PCR for a specific region of the gene, two separated bands can be seen on the gel. (wikipedia.org)
  • However, when the gene is mutated it is thought that this repair function may become disabled thus leading to more DNA replication errors and cancerous growth. (cancerindex.org)
  • One explanation for this disparity is that over 25%[citation needed] of genes on the inactivated X chromosome remain expressed, thus providing women with added protection against defective genes coded by the X-chromosome. (wikipedia.org)
  • With LH attached, the receptor shifts conformation and thus mechanically activates the G protein, which detaches from the receptor and activates the cAMP system. (wikipedia.org)
  • ovarian cancer
  • Skewed somatic X inactivation (XCI), X-linked gene overexpression and abnormal X content have been associated with breast and ovarian cancer. (ubc.ca)
  • Overall, expression was greatly increased for genes subject to inactivation but not increased in genes that escape inactivation for most ovarian cancer cell lines. (ubc.ca)
  • Queen's University, 2003 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE in THE FACULTY OF GRADUATE STUDIES (Medical Genetics) THE UNIVERSITY OF BRITISH COLUMBIA November 2007  Sara Helen Alison Harbord, 2007 ii Abstract Skewed somatic X inactivation (XCI), X-linked gene overexpression and abnormal X content have been associated with breast and ovarian cancer. (ubc.ca)
  • endogenous
  • Moreover, the synthetic androgens mibolerone and metribolone (R-1881), the endogenous androgen 11-ketotestoterone, and the other steroid hormones estradiol and cortisol are all ineffective competitors for the receptor. (wikipedia.org)
  • multifocal
  • A more recent study showed a high frequency of the same inactivation pattern (nine of 11 cases), which suggests that individual tumors arise from a single clone and that intraglandular metastasis may play an important role in the formation of multifocal PTCs 12. (immune-source.com)
  • loci
  • DNA FISH signals from Xist loci are shown in yellow color, marking both active and inactive X-chromosomes (Xa, Xi). (wikipedia.org)
  • MeCP2 has been implicated in regulation of imprinted genes and loci that include UBE3A and DLX5. (wikipedia.org)
  • males
  • SRY gene effects normally take place 6-8 weeks after foetus formation and inhibits the female anatomical structural growth in males. (wikipedia.org)
  • It is thought that X inactivation in XX males may account for the genital ambiguities and incomplete masculinization seen in SRY-positive XX males. (wikipedia.org)
  • Males typically have one X chromosome and one Y chromosome in each diploid cell of their bodies. (wikipedia.org)
  • In most XX males the SRY gene is present. (wikipedia.org)
  • tissue
  • Considering the fact that once one X chromosome is inactivated in a cell, all other cells derived from it will have the same X chromosome inactivated, this approach becomes a great tool to differentiate a monoclonal population from a polyclonal one in a female tissue. (wikipedia.org)
  • Although in vitro experiments indicate that androgens inhibit breast cell growth ( 1 , 2 ), higher circulating androgen levels in breast cancer cases compared with controls ( 3 ) point to a possible adverse influence of androgenic stimulation in breast cancer tissue. (aacrjournals.org)
  • ZIP9 membrane androgen receptor was first discovered in Atlantic croaker (Micropogonias undulatus) brain, ovary and testicular tissues and named "AR2" in 1999, together with another androgen receptor which was found only in brain tissue, and it was named "AR1" in that time. (wikipedia.org)
  • ZIP9 influxes zinc ions into the cytosol and its gene is expressed almost in every tissue of human body. (wikipedia.org)
  • Synthetic LXR agonist GW3965 improves glucose tolerance in a murine model of diet-induced obesity and insulin resistance by regulating genes involved in glucose metabolism in liver and adipose tissue. (wikipedia.org)
  • mosaic
  • The normal human female as a mosaic of X-chromosome activity: studies using the gene for G-6-PD-deficiency as a marker. (springer.com)
  • 2 Cells expressing the mutant X-chromosome are interspersed with cells expressing the normal X-chromosome, creating a mosaic pattern with the proportion of cells expressing the mutant X-chromosome determining the extent and severity of disease. (arvojournals.org)
  • XIST
  • The human XIST gene: analysis of a 17 kb inactive X-specific RNA that contains conserved repeats and is highly localized within the nucleus. (springer.com)
  • One sample did not localize XIST to the inactive X and three of five genes subject to inactivation were overexpressed. (ubc.ca)
  • The figure shows confocal microscopy images from a combined RNA-DNA FISH experiment for Xist in fibroblast cells from adult female mouse, demonstrating that Xist RNA is coating only one of the X-chromosomes. (wikipedia.org)
  • RNA FISH signals from Xist RNA are shown in red color, marking the inactive X-chromosome (Xi). (wikipedia.org)
  • The second is that Xce acts as a binding site for dosage factors that will affect XIST gene and Tsix expression (long non-coding RNAs involved in X chromosome inactivation). (wikipedia.org)
  • mice
  • Previous findings that duplicated Toll-like receptor 7 ( Tlr7 ) promotes lupus-like disease in male BXSB mice prompted us to evaluate TLR7 in human SLE. (pnas.org)
  • Skewed X inactivation in mice is controlled by the Xce gene on the X chromosome. (wikipedia.org)
  • In mice, loss-of-function of Pten leads to high-grade PIN and/or carcinoma and can synergize with inactivation of other relevant genes, such as Nkx3.1, p27 kip1 , or p53 , in prostate cancer progression ( 15 , 22 - 25 ). (aacrjournals.org)
  • Because the adrenal glands provide an alternative source of androgens that may be used in the absence of testosterone ( 26 ), we also did bilateral adrenalectomy along with castration to fully deplete all circulating androgens in several mice. (aacrjournals.org)
  • SRY gene has little in common with sex determination genes of other model organisms, and mice are the main model research organisms that can be utilized for its study. (wikipedia.org)
  • Scientists have created a DKK1 knockout model in mice that revealed the effects of this gene. (wikipedia.org)
  • DAX1
  • DAX1 represses masculinizing genes, therefore, if there is a loss of function of DAX1 then testes can develop in an XX individual. (wikipedia.org)
  • Pten
  • We have been investigating the evolution of androgen-independent prostate cancer in vivo using a mouse model based on the loss-of-function of the Nkx3.1 homeobox gene and the Pten tumor suppressor. (aacrjournals.org)
  • PTEN maps to human chromosome region 10q23, which is deleted at high frequency in prostate cancer ( 8 ), and loss of PTEN protein expression is a frequent occurrence in advanced prostate cancer ( 20 , 21 ). (aacrjournals.org)
  • Previously, we have found that loss-of-function of Nkx3.1 and Pten leads to PIN and cancer with aging, as well as androgen independence following castration ( 22 , 25 ). (aacrjournals.org)
  • Genes corresponding to PTEN (orthologs) have been identified in most mammals for which complete genome data are available. (wikipedia.org)
  • PTEN acts as a tumor suppressor gene through the action of its phosphatase protein product. (wikipedia.org)
  • in fact, up to 70% of men with prostate cancer are estimated to have lost a copy of the PTEN gene at the time of diagnosis. (wikipedia.org)
  • amplification
  • Amplification of the CCND1 gene is present in: non-small cell lung cancers (30-46%) head and neck squamous cell carcinomas (30-50%) pancreatic carcinomas (25%) bladder cancer (15%) pituitary adenomas (49-54%) breast carcinoma (13%) Cyclin D1 overexpression is strongly correlated to ER+ breast cancer and deregulation of cyclin D1 is associated with hormone therapy resistance in breast cancer. (wikipedia.org)
  • tissues
  • LXRβ is expressed in almost all tissues and organs, hence the early name UR (ubiquitous receptor). (wikipedia.org)
  • Cancer is a classic example of what evolutionary biologists call multilevel selection: at the level of the organism, cancer is usually fatal so there is selection for genes and the organization of tissues that suppress cancer. (wikipedia.org)
  • human
  • Although the sex effect has often been attributed to sex hormones, the fact that XXY male subjects have approximately a 14-fold higher risk of developing SLE than 46 XY men indicates that X-linked genes may be risk factors for human SLE ( 3 ). (pnas.org)
  • Human T-cell gamma chain genes: organization, diversity, and rearrangement. (springer.com)
  • The process and possible outcomes of random X chromosome inactivation in female human embryonic cells undergoing mitosis . (wikipedia.org)
  • Gene knockdown of Oct-4 promotes differentiation, thereby demonstrating a role for these factors in human embryonic stem cell self-renewal. (wikipedia.org)
  • The human TUBB3 gene is located on chromosome 16q24.3, and consists of 4 exons that transcribe a protein of 450aa. (wikipedia.org)
  • The human LXRα gene is located on chromosome 11p11.2, while the LXRβ gene is located on chromosome 19q13.3. (wikipedia.org)
  • Crystal structure of human liver X receptor β(LXRβ) forming heterodimer with its partner retinoid X receptor α(RXRα) on its cognate element, an AGGTCA direct repeat spaced by 4 nt shows an extended X-shaped arrangement, with DNA- and ligand-binding domains crossed, in contrast to the parallel domain arrangement of other NRs that bind an AGGTCA direct repeat spaced by 1 nt. (wikipedia.org)
  • BRCA1 and BRCA1 (/ˌbrækəˈwʌn/) are a human gene and its protein product, respectively. (wikipedia.org)
  • The human BRCA1 gene is located on the long (q) arm of chromosome 17 at region 2 band 1, from base pair 41,196,312 to base pair 41,277,500 (Build GRCh37/hg19) (map). (wikipedia.org)
  • inactive
  • The inactive X chromosome is silenced by it being packaged in such a way that it has a transcriptionally inactive structure called heterochromatin . (wikipedia.org)
  • normal
  • Despite the haploinsufficiency of CTCF, X chromosome inactivation was normal. (bmj.com)
  • The normal gene plays a role in repairing breaks in DNA. (cancerindex.org)
  • mild androgen insensitivity syndrome (MAIS) is indicated when the external genitalia are that of a normal male, and partial androgen insensitivity syndrome (PAIS) is indicated when the external genitalia are partially, but not fully, masculinized. (wikipedia.org)
  • Researchers have not yet determined which genes are targeted by the MeCP2 protein, but such genes are probably important for the normal function of the central nervous system. (wikipedia.org)
  • When the X with the SRY gene combines with a normal X from the mother during fertilization, the result is an XX male. (wikipedia.org)
  • binds
  • Cyclin D1 also binds to histone acetylases and histone deacetylases to regulate cell proliferation and cell differentiation genes in the early to mid-G1 phase. (wikipedia.org)
  • After activation, LXR binds to LXR response element (LXRE), usually a variant of the idealized sequence AGGTCAN4AGGTCA, in the promoters of LXRs' target genes. (wikipedia.org)
  • cell
  • Expression was inconsistent between different genes and among cell lines, ranging from a 2 to 300-fold increase compared to a control. (ubc.ca)
  • In the early blastocyst , this initial, imprinted X-inactivation is reversed in the cells of the inner cell mass (which give rise to the embryo), and in these cells both X chromosomes become active again. (wikipedia.org)
  • A mouse cell with the Xce genotype ad will have a greater number of the a-carrying than d-carrying X chromosomes inactivated, because the d-carrying X chromosome is less likely to be inactivated. (wikipedia.org)
  • For a cell to respond to LH only a small percentage (≈1%) of receptor sites need to be activated. (wikipedia.org)
  • The influx of calcium ions into the cell can initiate a myriad of calcium-dependent processes including muscle contraction, gene expression, and secretion. (wikipedia.org)
  • membrane
  • A study in 2014 utilised the latest research technologies to clone and express a particular cDNA of the female Atlantic croaker ovaries, which encoded a protein showing the characteristics of the canonical isoform of ZIP9, as a novel membrane androgen receptor(mAR). (wikipedia.org)
  • Like other GPCRs, the LHCG receptor possess seven membrane-spanning domains or transmembrane helices. (wikipedia.org)
  • Upregulation refers to the increase in the number of receptor sites on the membrane. (wikipedia.org)