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X Chromosome (x + chromosome)
Kinds of X Chromosome Terms modified by X Chromosome Selected AbstractsDIFFERENTIAL PATTERNS OF INTROGRESSION ACROSS THE X CHROMOSOME IN A HYBRID ZONE BETWEEN TWO SPECIES OF HOUSE MICEEVOLUTION, Issue 9 2004Bret A. Payseur Abstract A complete understanding of the speciation process requires the identification of genomic regions and genes that confer reproductive barriers between species. Empirical and theoretical research has revealed two important patterns in the evolution of reproductive isolation in animals: isolation typically arises as a result of disrupted epistatic interactions between multiple loci and these disruptions map disproportionately to the X chromosome. These patterns suggest that a targeted examination of natural gene flow between closely related species at X-linked markers with known positions would provide insight into the genetic basis of speciation. We take advantage of the existence of genomic data and a well-documented European zone of hybridization between two species of house mice, Mus domesticus and M. musculus, to conduct such a survey. We evaluate patterns of introgression across the hybrid zone for 13 diagnostic X-linked loci with known chromosomal positions using a maximum likelihood model. Interlocus comparisons clearly identify one locus with reduced introgression across the center of the hybrid zone, pinpointing a candidate region for reproductive isolation. Results also reveal one locus with high frequencies of M. domesticus alleles in populations on the M. musculus side of the zone, suggesting the possibility that positive selection may act to drive the spread of alleles from one species on to the genomic background of the other species. Finally, cline width and cline center are strongly positively correlated across the X chromosome, indicating that gene flow of the X chromosome may be asymmetrical. This study highlights the utility of natural populations of hybrids for mapping speciation genes and suggests that the middle of the X chromosome may be important for reproductive isolation between species of house mice. [source] Suspected involvement of the X chromosome in placental mesenchymal dysplasiaCONGENITAL ANOMALIES, Issue 4 2002Masayoshi Arizawa ABSTRACT, So far, 46 cases of placental mesenchymal dysplasia have been reported worldwide. We encountered 15 cases of placental mesenchymal dysplasia (PMD) including 7 cases delivered in our hospital. The incidence of PMD in our hospital was therefore, 7/30, 758 (0.02%). The PMD had a peculiar appearance. In the gross findings, large placenta with intestine-like dilatation of the vessels on the fetal side was reported. Microscopically, cistern-like dilatation of the stem villi, fetal artery thrombosis, and villous hemorrhage were reported. However, we believe most of these findings are secondary rather than the primary of mesenchymal dysplasia. Therefore, we investigated 15 other cases of mesenchymal dysplasia, and found including vascular abnormality of the stem, intermediate and terminal villi in all case of PMD. The abnormality was observed in the vessels of the periphery of the stem villi and their vessel walls were thin and appeared weak. The intermediate villous vessels were unusual, tangled. The terminal villous abnormalities showed chorangiosis and stromal hyperplasia. These findings are mesenchymal dysplasia origin. Moreover, PMD showed female-predominant. 14/15 was female among our cases, We discuss the relationship between mesenchymal dysplasia and the X chromosome in this paper. [source] Turner syndrome: Neuroimaging findings: Structural and functionalDEVELOPMENTAL DISABILITIES RESEARCH REVIEW, Issue 4 2009Ronan Mullaney Abstract Neuroimaging studies of Turner syndrome can advance our understanding of the X chromosome in brain development, and the modulatory influence of endocrine factors. There is increasing evidence from neuroimaging studies that TX individuals have significant differences in the anatomy, function, and metabolism of a number of brain regions; including the parietal lobe; cerebellum, amygdala, hippocampus; and basal ganglia; and perhaps differences in "connectivity" between frontal and parieto-occipital regions. Finally, there is preliminary evidence that genomic imprinting, sex hormones and growth hormone have significant modulatory effects on brain maturation in TS. © 2009 Wiley-Liss, Inc. Dev Disabil Res Rev 2009;15:279,283. [source] The cognitive phenotype in Klinefelter syndrome: A review of the literature including genetic and hormonal factorsDEVELOPMENTAL DISABILITIES RESEARCH REVIEW, Issue 4 2009Richard Boada Abstract Klinefelter syndrome (KS) or 47,XXY occurs in ,1 in 650 males. Individuals with KS often present with physical characteristics including tall stature, hypogonadism, and fertility problems. In addition to medical findings, the presence of the extra X chromosome can lead to characteristic cognitive and language deficits of varying severity. While a small, but significant downward shift in mean overall IQ has been reported, the general cognitive abilities of patients with KS are not typically in the intellectual disability range. Most studies support that males with KS have an increased risk of language disorders and reading disabilities. Results of other studies investigating the relationship between verbal and nonverbal/spatial cognitive abilities have been mixed, with differing results based on the age and ascertainment method of the cohort studied. Executive function deficits have been identified in children and adults with KS, however, the research in this area is limited and further investigation of the neuropsychological profile is needed. In this article, we review the strengths and weaknesses of previous cognitive and neuropsychological studies in males with KS in childhood and adulthood, provide historical perspective of these studies, and review what is known about how hormonal and genetic factors influence cognitive features in 47,XXY/KS. © 2009 Wiley-Liss, Inc. Dev Disabil Res Rev 2009;15:284,294. [source] The neuroanatomy and neuroendocrinology of fragile X syndromeDEVELOPMENTAL DISABILITIES RESEARCH REVIEW, Issue 1 2004David Hessl Abstract Fragile X syndrome (FXS), caused by a single gene mutation on the X chromosome, offers a unique opportunity for investigation of gene,brain,behavior relationships. Recent advances in molecular genetics, human brain imaging, and behavioral studies have started to unravel the complex pathways leading to the cognitive, psychiatric, and physical features that are unique to this syndrome. In this article, we summarize studies focused on the neuroanatomy and neuroendocrinology of FXS. A review of structural imaging studies of individuals with the full mutation shows that several brain regions are enlarged, including the hippocampus, amygdala, caudate nucleus, and thalamus, even after controlling for overall brain volume. These regions mediate several cognitive and behavioral functions known to be aberrant in FXS such as memory and learning, information and sensory processing, and social and emotional behavior. Two regions, the cerebellar vermis, important for a variety of cognitive tasks and regulation of motor behavior, and the superior temporal gyrus, involved in processing complex auditory stimuli, are reported to be reduced in size relative to controls. Functional imaging, typically limited to females, has emphasized that individuals with FXS do not adequately recruit brain regions that are normally utilized by unaffected individuals to carry out various cognitive tasks, such as arithmetic processing or visual memory tasks. Finally, we review a number of neuroendocrine studies implicating hypothalamic dysfunction in FXS, including abnormal activation of the hypothalamic,pituitary,adrenal (HPA) axis. These studies may help to explain the abnormal stress responses, sleep abnormalities, and physical growth patterns commonly seen in affected individuals. In the future, innovative longitudinal studies to investigate development of neurobiologic and behavioral features over time, and ultimately empirical testing of pharmacological, behavioral, and even molecular genetic interventions using MRI are likely to yield significant positive changes in the lives of persons with FXS, as well as increase our understanding of the development of psychiatric and learning problems in the general population. MRDD Research Reviews 2004;10:17,24. © 2004 Wiley-Liss, Inc. [source] An Xp; Yq Translocation Causing a Novel Contiguous Gene Syndrome in Brothers with Generalized Epilepsy, Ichthyosis, and Attention DeficitsEPILEPSIA, Issue 12 2003Michael J. Doherty Summary:,Purpose: We describe two brothers with generalized epilepsy, attention deficits, congenital ichthyosis, and Leri,Weill dyschondrosteosis who harbor an unusual Xp; Yq translocation chromosome, resulting in a novel contiguous gene syndrome because of deletion of genes from the distal short arm of the X chromosome. Methods: Physical examination, neuropsychologic testing, EEG, and neuroimaging studies were performed. Because of their unusual phenotype, karyotyping, fluorescence in situ hybridization, and further molecular analyses were carried out to refine the break points of the underlying unbalanced sex chromosome rearrangement. Results: The subjects had generalized epilepsy, X-linked ichthyosis, Madelung deformities, mesomelia, normal intelligence, and attention deficits. The brothers' karyotype was unbalanced; they inherited a maternal derivative X chromosome. Deleted distal Xp genes included short-stature homeobox on the X chromosome (SHOX), aryl sulfatase E (ARSE), variably charged X-chromosome mRNA gene A (VCX-A), and steroid sulfatase (STS). The final karyotype was 46,Y,der(X)t(X; Y)(p22.3; q11.2).ish der(X) (DXZ1+, KAL+, STS-, SHOX-) mat. Conclusions: Loss of distal contiguous Xp genes resulted in a syndrome comprising bony deformities, ichthyosis, attention problems, and generalized epilepsy. Candidate epilepsy genes within the deleted segment, such as ASMT, a gene involved in the final synthesis of melatonin, are discussed. Cytogenetic analyses should be included in the clinical evaluation of patients with generalized epilepsy and complex phenotypes. [source] SELF-IMPOSED SILENCE: PARENTAL ANTAGONISM AND THE EVOLUTION OF X-CHROMOSOME INACTIVATIONEVOLUTION, Issue 3 2006David Haig Abstract A model is proposed for the evolution of X-chromosome inactivation (XCI) in which natural selection initially favors the silencing of paternally derived alleles of X-linked demand inhibitors. The compensatory upregulation of maternally derived alleles establishes a requirement for monoallelic expression in females. For this reason, XCI is self-reinforcing once established. However, inactivation of a particular X chromosome is not. Random XCI (rXCI) is favored over paternal XCI because rXCI reduces the costs of functional hemizygosity in females. Once present, rXCI favors the evolution of locus-by-locus imprinting of X-linked loci, which creates an evolutionary dynamic in which different chromosomes compete to remain active. [source] DIFFERENTIAL PATTERNS OF INTROGRESSION ACROSS THE X CHROMOSOME IN A HYBRID ZONE BETWEEN TWO SPECIES OF HOUSE MICEEVOLUTION, Issue 9 2004Bret A. Payseur Abstract A complete understanding of the speciation process requires the identification of genomic regions and genes that confer reproductive barriers between species. Empirical and theoretical research has revealed two important patterns in the evolution of reproductive isolation in animals: isolation typically arises as a result of disrupted epistatic interactions between multiple loci and these disruptions map disproportionately to the X chromosome. These patterns suggest that a targeted examination of natural gene flow between closely related species at X-linked markers with known positions would provide insight into the genetic basis of speciation. We take advantage of the existence of genomic data and a well-documented European zone of hybridization between two species of house mice, Mus domesticus and M. musculus, to conduct such a survey. We evaluate patterns of introgression across the hybrid zone for 13 diagnostic X-linked loci with known chromosomal positions using a maximum likelihood model. Interlocus comparisons clearly identify one locus with reduced introgression across the center of the hybrid zone, pinpointing a candidate region for reproductive isolation. Results also reveal one locus with high frequencies of M. domesticus alleles in populations on the M. musculus side of the zone, suggesting the possibility that positive selection may act to drive the spread of alleles from one species on to the genomic background of the other species. Finally, cline width and cline center are strongly positively correlated across the X chromosome, indicating that gene flow of the X chromosome may be asymmetrical. This study highlights the utility of natural populations of hybrids for mapping speciation genes and suggests that the middle of the X chromosome may be important for reproductive isolation between species of house mice. [source] Turner syndrome and the evolution of human sexual dimorphismEVOLUTIONARY APPLICATIONS (ELECTRONIC), Issue 3 2008Bernard Crespi Abstract Turner syndrome is caused by loss of all or part of an X chromosome in females. A series of recent studies has characterized phenotypic differences between Turner females retaining the intact maternally inherited versus paternally inherited X chromosome, which have been interpreted as evidence for effects of X-linked imprinted genes. In this study I demonstrate that the differences between Turner females with a maternal X and a paternal X broadly parallel the differences between males and normal females for a large suite of traits, including lipid profile and visceral fat, response to growth hormone, sensorineural hearing loss, congenital heart and kidney malformations, neuroanatomy (sizes of the cerebellum, hippocampus, caudate nuclei and superior temporal gyrus), and aspects of cognition. This pattern indicates that diverse aspects of human sex differences are mediated in part by X-linked genes, via genomic imprinting of such genes, higher rates of mosaicism in Turner females with an intact X chromosome of paternal origin, karyotypic differences between Turner females with a maternal versus paternal X chromosome, or some combination of these phenomena. Determining the relative contributions of genomic imprinting, karyotype and mosaicism to variation in Turner syndrome phenotypes has important implications for both clinical treatment of individuals with this syndrome, and hypotheses for the evolution and development of human sexual dimorphism. [source] Effects of sex chromosome aneuploidy on male sexual behaviorGENES, BRAIN AND BEHAVIOR, Issue 6 2008J. H. Park Incidence of sex chromosome aneuploidy in men is as high as 1:500. The predominant conditions are an additional Y chromosome (47,XYY) or an additional X chromosome (47,XXY). Behavioral studies using animal models of these conditions are rare. To assess the role of sex chromosome aneuploidy on sexual behavior, we used mice with a spontaneous mutation on the Y chromosome in which the testis-determining gene Sry is deleted (referred to as Y,) and insertion of a Sry transgene on an autosome. Dams were aneuploid (XXY,) and the sires had an inserted Sry transgene (XYSry). Litters contained six male genotypes, XY, XYY,, XXSry, XXY,Sry, XYSry and XYY,Sry. In order to eliminate possible differences in levels of testosterone, all of the subjects were castrated and received testosterone implants prior to tests for male sex behavior. Mice with an additional copy of the Y, chromosome (XYY,) had shorter latencies to intromit and achieve ejaculations than XY males. In a comparison of the four genotypes bearing the Sry transgene, males with two copies of the X chromosome (XXSry and XXY,Sry) had longer latencies to mount and thrust than males with only one copy of the X chromosome (XYSry and XYY,Sry) and decreased frequencies of mounts and intromissions as compared with XYSry males. The results implicate novel roles for sex chromosome genes in sexual behaviors. [source] Female receptivity phenotype of icebox mutants caused by a mutation in the L1-type cell adhesion molecule neuroglianGENES, BRAIN AND BEHAVIOR, Issue 8 2005A. Carhan Relatively little is known about the genes and brain structures that enable virgin female Drosophila to make the decision to mate or not. Classical genetic approaches have identified several mutant females that have a reluctance-to-mate phenotype, but most of these have additional behavioral defects. However, the icebox (ibx) mutation was previously reported to lower the sexual receptivity of females, without apparently affecting any other aspect of female behavior. We have shown that the ibx mutation maps to the 7F region of the Drosophila X chromosome to form a complex complementation group with both lethal and viable alleles of neuroglian (nrg). The L1-type cell adhesion molecule encoded by nrg consists of six immunoglobulin-like domains, five fibronectin-like domains, one transmembrane domain and one alternatively spliced intracellular domain. The ibx strain has a missense mutation causing a glycine-to-arginine change at amino acid 92 in the first immunoglobulin domain of nrg. Defects in the central brain of ibx mutants are similar to those observed in another nrg mutant, central brain deranged1 (ceb1). However, both ceb1 homozygous and ceb1/ibx heterozygous females are receptive. The expression of a transgene containing the non-neural isoform of nrg rescues both the receptivity and the brain structure phenotypes of ibx females. [source] Prognostic significance of secondary cytogenetic alterations in follicular lymphomasGENES, CHROMOSOMES AND CANCER, Issue 12 2008Nathalie A. Johnson Follicular lymphoma (FL) is an indolent lymphoma with a long median survival. Transformation to a more aggressive histology (TLy) is a major cause of mortality. The critical events leading to TLy are unknown. We assessed the prognostic significance of secondary cytogenetic alterations on overall survival (OS) and transformation from 210 diagnostic FL biopsies. We analyzed serial and transformed karyotypes for recurrent alterations that predict transformation. Over 10 years, 31% of cases developed TLy. The only alteration in diagnostic karyotypes that correlated with an inferior OS was an additional X chromosome in males only (P = 0.005) suggesting that other mechanisms including epigenetic factors and over-expression of genes on the X chromosome may play a role in FL pathogenesis. In transformed karyotypes, 8q24 (MYC) translocations were common (14/37) and resulted in a median survival of 3 months posttransformation (P = 0.01). In serially obtained biopsies (28 pts), 43% of the later biopsies lacked the cytogenetic alterations found in the original FL karyotype, suggesting that karyotypic progression of FL is not strictly linear in all cases. Consequently, studying clonal evolution in FL using serial biopsies may not represent the full complexity of genetic alterations leading to transformation. © 2008 Wiley-Liss, Inc. [source] MLL/SEPTIN6 chimeric transcript from inv ins(X;11)(q24;q23q13) in acute monocytic leukemia: Report of a case and review of the literatureGENES, CHROMOSOMES AND CANCER, Issue 1 2003Hee-Jin Kim Rearrangements of the MLL gene on chromosome 11, band q23, are one of the most common genetic changes in acute leukemia. Reciprocal translocation is the most common form of MLL rearrangement, and the partner genes in MLL translocation are notably diverse. Involvement of the SEPTIN6 gene on Xq24 in MLL rearrangements occurs very rarely, with only six cases having been documented in the literature. Of note, the MLL/SEPTIN6 rearrangements in these cases were cryptic or complex, and it was shown that the 5,- MLL/SEPTIN6 -3, transcript resides on the derivative X chromosome rather than on the derivative chromosome 11 as in the majority of cases of MLL translocations. These observations suggested that MLL and SEPTIN6 reside on their respective chromosome loci in reverse orientation, that is, centromere-to-telomere and telomere-to-centromere, respectively. We here report a case of acute monocytic leukemia with inv ins(X;11)(q24;q23q13) in a 29-month-old child. Fluorescence in situ hybridization study revealed the break-apart 5,- MLL segment to be translocated to the derivative X chromosome, and reverse transcriptase,polymerase chain reaction followed by sequencing analysis confirmed the 5,- MLL/SEPTIN6 -3, chimeric transcript. This case is the first to provide direct cytogenetic evidence for the salient nature of the MLL/SEPTIN6 rearrangement. We reviewed clinical and cytogenetic features of all cases of 11q23 and Xq22,24 rearrangements reported up to now, including six cases where the involvement of the SEPTIN6 gene was confirmed by molecular techniques. © 2003 Wiley-Liss, Inc. [source] Molecular cytogenetic characterization of early and late renal cell carcinomas in Von Hippel-Lindau disease ,GENES, CHROMOSOMES AND CANCER, Issue 1 2001John L. Phillips Deletions of 3p25, gains of chromosomes 7 and 10, and isochromosome 17q are known cytogenetic aberrations in sporadic renal cell carcinoma (RCC). In addition, a majority of RCCs have loss of heterozygosity (LOH) of the Von Hippel-Lindau (VHL) gene located at chromosome band 3p25. Patients who inherit a germline mutation of the VHL gene can develop multifocal RCCs and other solid tumors, including malignancies of the pancreas, adrenal medulla, and brain. VHL tumors follow the two-hit model of tumorigenesis, as LOH of VHL, a classic tumor suppressor gene, is the critical event in the development of the neoplastic phenotype. In an attempt to define the cytogenetic aberrations from early tumors to late RCC further, we applied spectral karyotyping (SKY) to 23 renal tumors harvested from 6 unrelated VHL patients undergoing surgery. Cysts and low-grade solid lesions were near-diploid and contained 1,2 reciprocal translocations, dicentric chromosomes, and/or isochromosomes. A variety of sole numerical aberrations included gains of chromosomes 1, 2, 4, 7, 10, 13, 21, and the X chromosome, although no tumors had sole numerical losses. Three patients shared a breakpoint at 2p21,22, and three others shared a dicentric chromosome 9 or an isochromosome 9q. In contrast to the near-diploidy of the low-grade lesions, a high-grade lesion and its nodal metastasis were markedly aneuploid, revealed loss of VHL by fluorescence in situ hybridization (FISH), and contained recurrent unbalanced translocations and losses of chromosome arms 2q, 3p, 4q, 9p, 14q, and 19p as demonstrated by comparative genomic hybridization (CGH). By combining SKY, CGH, and FISH of multiple tumors from the same VHL kidney, we have begun to identify chromosomal aberrations in the earliest stages of VHL-related renal cell tumors. Our current findings illustrate the cytogenetic heterogeneity of different VHL lesions from the same kidney, which supports the multiclonal origins of hereditary RCCs. Published 2001 Wiley-Liss, Inc. [source] De Novo DNA methylation independent establishment of maternal imprint on X chromosome in mouse oocytesGENESIS: THE JOURNAL OF GENETICS AND DEVELOPMENT, Issue 12 2008Hatsune Chiba Mouse blastocyst stage embryo stained for histone H3 lysine-27 trimethylation (red) and DNA (blue). H3K27me3 marks the inactive X chromosome. The study by Chiba et al. in this issue suggests that de novo DNA methyltransferases are dispensable for setting the imprint on the maternally-derived X chromsome in growing oocytes. See Chiba et al. in this issue. [source] Testing association for markers on the X chromosome,GENETIC EPIDEMIOLOGY, Issue 8 2007Gang Zheng Abstract Test statistics for association between markers on autosomal chromosomes and a disease have been extensively studied. No research has been reported on performance of such test statistics for association on the X chromosome. With 100,000 or more single-nucleotide polymorphisms (SNPs) available for genome-wide association studies, thousands of them come from the X chromosome. The X chromosome contains rich information about population history and linkage disequilibrium. To identify X-linked marker susceptibility to a disease, it is important to study properties of various statistics that can be used to test for association on the X chromosome. In this article, we compare performance of several approaches for testing association on the X chromosome, and examine how departure from Hardy-Weinberg equilibrium would affect type I error and power of these association tests using X-linked SNPs. The results are applied to the X chromosome of Klein et al. [2005], a genome-wide association study with 100K SNPs for age-related macular degeneration. We found that a SNP (rs10521496) covered by DIAPH2, known to cause premature ovarian failure (POF) in females, is associated with age-related macular degeneration. Genet. Epidemiol. 2007. Published 2007 Wiley-Liss, Inc. [source] Pathophysiological significance of senescence marker protein-30GERIATRICS & GERONTOLOGY INTERNATIONAL, Issue 2010Naoki Maruyama A novel rat liver protein of 30 kDa, SMP30 decreases with aging. This protein is expressed most prominently in the liver and kidneys among the various organs. Its gene is located on the X chromosome. No functional domain was recognized in the entire amino acid sequence. Recently, we found a homology between rat SMP30 and two species of bacterial gluconolactonase (EC 3.1.1.17). The lactonase reaction with l -gulono-,-lactone is the penultimate step in vitamin C (l -ascorbic acid) biosynthesis. SMP30-knockout (KO) mice fed a vitamin C-deficient diet displayed symptoms of scurvy. In SMP30-KO mice, hepatocytes were more susceptible to apoptosis induced by TNF-, plus actinomycin D than hepatocytes from wild-type mice. Two morphological features considered to be a hallmark of senescence are apparent in SMP30-KO mice. At 12 months of age, SMP30-knockout mice had clearly visible deposits of lipofuscin and senescence-associated ,-galactosidase (SA-,-GAL) in their renal tubular epithelia. These features are compatible with high electron dense deposits in lysosomes. This observation suggests that the SMP30-knockout mouse is a useful model of ordinal senescence. Geriatr Gerontol Int 2010; 10 (Suppl. 1): S88,S98. [source] Can Turner syndrome teach us about the pathogenesis of chronic cholestasis?HEPATOLOGY, Issue 5 2004Piotr Milkiewicz The mechanisms that cause the female predominance of primary biliary cirrhosis (PBC) are uncertain, but the X chromosome includes genes involved in immunological tolerance. We assessed the rate of X monosomy in peripheral white blood cells from 100 women with PBC, 50 with chronic hepatitis C, and 50 healthy controls, by fluorescence in-situ hybridisation. Frequency of X monosomy increased with age in all groups, but was significantly higher in women with PBC than in controls (p<0.0001); age-adjusted back-transformed mean frequencies were 0.050 (95% CI 0.046-0.055) in women with PBC, 0.032 (0.028-0.036) in those with chronic hepatitis C, and 0.028 (0.025-0.032) in controls. We suggest that haploinsufficiency for specific X-linked genes leads to female susceptibility to PBC. [source] Role of X chromosome defects in primary biliary cirrhosisHEPATOLOGY RESEARCH, Issue 2007Pietro Invernizzi Similar to the majority of autoimmune conditions, primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease characterized by a striking female predominance; it is characterized by high titer serum autoantibodies to mitochondrial antigens, elevated serum immunoglobulin M, progressive destruction of intrahepatic bile ducts, and ultimately liver cirrhosis and failure. Familiarity and high concordance rates for the disease among monozygotic twins strongly support the role of genetics in the disease. Experimental efforts have been dedicated by our and other research groups to investigate the role of X chromosome abnormalities (i.e. monosomyrates and inactivation patterns) in autoimmunity. Our recent work has demonstrated enhanced X monosomy in women with PBC as well as two other female-predominant autoimmune diseases, systemic sclerosis and autoimmune thyroid disease. We will review herein the most recent evidence on the role of the X chromosome in PBC onset and discuss the potential implications. Future developments of these findings will be discussed. [source] Mutation frequencies of X-linked mental retardation genes in families from the EuroMRX consortium,,HUMAN MUTATION, Issue 2 2007Arjan P.M. de Brouwer Abstract The EuroMRX family cohort consists of about 400 families with non-syndromic and 200 families with syndromic X-linked mental retardation (XLMR). After exclusion of Fragile X (Fra X) syndrome, probands from these families were tested for mutations in the coding sequence of 90 known and candidate XLMR genes. In total, 73 causative mutations were identified in 21 genes. For 42% of the families with obligate female carriers, the mental retardation phenotype could be explained by a mutation. There was no difference between families with (lod score >2) or without (lod score <2) significant linkage to the X chromosome. For families with two to five affected brothers (brother pair=BP families) only 17% of the MR could be explained. This is significantly lower (P=0.0067) than in families with obligate carrier females and indicates that the MR in about 40% (17/42) of the BP families is due to a single genetic defect on the X chromosome. The mutation frequency of XLMR genes in BP families is lower than can be expected on basis of the male to female ratio of patients with MR or observed recurrence risks. This might be explained by genetic risk factors on the X chromosome, resulting in a more complex etiology in a substantial portion of XLMR patients. The EuroMRX effort is the first attempt to unravel the molecular basis of cognitive dysfunction by large-scale approaches in a large patient cohort. Our results show that it is now possible to identify 42% of the genetic defects in non-syndromic and syndromic XLMR families with obligate female carriers. © 2007 Wiley-Liss, Inc. [source] High-frequency haplotypes in the X chromosome locus TLR8 are associated with both CD and UC in femalesINFLAMMATORY BOWEL DISEASES, Issue 3 2009Masayuki Saruta MD Abstract Background: TNF-, and IL-1 have been associated with mucosal inflammation in both Crohn's disease (CD) and ulcerative colitis (UC). Innate immune defects have been associated with CD, specifically CARD15/NOD2. Recently, Toll-like receptor 8 (TLR8) signaling has been shown to enhance generation of both cytokines. Interestingly, TLR8 is located on the X chromosome and inflammatory bowel disease (IBD) has been associated with abnormalities of the X chromosome. The aim was to test whether TLR8 haplotypes are associated with IBD. Methods: Subjects (735 CD, 343 UC, 245 controls) were genotyped. Single nucleotide polymorphisms (SNPs) were chosen to tag common Caucasian haplotypes. Results: Both "risk (H4)" and "protective (H1)" TLR8 haplotypes were observed associated with CD in females. Eighteen percent of CD females had H4 compared with 9% of controls (P = 0.02). Fifty-nine percent of CD females had H1 compared with 72% of controls (P = 0.01). H1 was also negatively associated with UC in females (59% of UC, 72% of controls P = 0.03). Diplotype analysis of CD, UC, and all IBD in females revealed that 2 protective haplotypes (H1/H1) had a markedly diminished odds ratio, 0.4,0.5. The presence of a risk haplotype (H4 / not H1) had a significantly increased odds ratio, 2.0,2.2. Thus, the risk for IBD was 4,5 times higher in females with 1 risk haplotype than with the protective/protective diplotype. Conclusions: TLR8 is an X-linked IBD susceptibility gene with both common predisposing and protecting haplotypes. These associations further emphasize the importance of genetic variation in innate immunity as determinants, not only of CD, but of UC as well. (Inflamm Bowel Dis 2008) [source] SINE insertion polymorphism on the X chromosome differentiates Anopheles gambiae molecular formsINSECT MOLECULAR BIOLOGY, Issue 4 2005M. J. Barnes Abstract Polymorphic SINE insertions can be useful markers for assessing population structure and differentiation. Maque is a family of SINE elements which, based on bioinformatic analysis, was suggested to have been active recently in Anopheles gambiae, the major vector of malaria. Here, we report the development of polymorphic Maque insertions as population genetic markers in A. gambiae, and the use of these markers to better characterize divergence on the X chromosome between A. gambiae M and S molecular forms in populations from Burkina Faso and Mali. Our data are consistent with the recent activity of Maque. Phylogenetic analysis suggests that at least two recently active lineages may have a role in mediating genome evolution. We found differences in element insertion frequency and sequence between the M and S populations analysed. Significant differentiation was observed between these two groups across a 6 Mb region at the proximal (centromeric) end of the X chromosome. Locus-specific FST values ranged from 0.14 to 1.00 in this region, yet were not significantly different from zero in more distal locations on the X chromosome; the trend was consistent in populations from both geographical locales suggesting that differentiation is not due to local adaptation. Strong differentiation between M and S at the proximal end of the X chromosome, but not outside this region, suggests the action of selection counteracting limited gene flow between these taxa and supports their characterization as incipient species. [source] Epigenetic regulation and downstream targets of the Rhox5 homeobox geneINTERNATIONAL JOURNAL OF ANDROLOGY, Issue 5 2008S. Shanker Summary The discovery of the Rhox homeobox gene cluster on the X chromosome opens up new vistas in the regulation of reproductive processes in mammals. In mice, this cluster comprises more than 30 genes that are selectively expressed in reproductive tissues. A subset of Rhox genes are androgen and AR regulated in postnatal and adult Sertoli cells, making them candidates to mediate androgen-dependent steps during spermatogenesis. The best characterized of these androgen/AR-regulated genes is Rhox5 (Pem), the founding member of the Rhox gene cluster. Targeted deletion of Rhox5 in mice causes male subfertility marked by increased germ-cell apoptosis and decreased sperm count and motility. Microarray analyses identified a wide variety of genes regulated by Rhox5 in Sertoli cells. One of them is the tumour suppressor UNC5C, a pro-apoptotic molecule previously only known to be involved in brain development. Targeted deletion of Unc5c causes decreased germ-cell apoptosis in postnatal and adult testes, indicating that it also has a role in spermatogenesis and supporting a model in which Rhox5 promotes germ-cell survival by downregulating Unc5c. Rhox5 has two independently regulated promoters that have distinct expression patterns. The unique tissue-specific and developmentally regulated transcription pattern of these two promoters appear to be controlled by DNA methylation. Both promoters are methylated in tissues in which they are not expressed, suggesting that DNA methylation serves to repress Rhox5 expression in inappropriate cell types and tissues. In summary, the Rhox gene cluster is an epigenetically regulated set of genes encoding a large number of transcription factors that are strong candidates to regulate gametogenesis and other aspects of reproduction. [source] Expression of SPANX proteins in human-ejaculated spermatozoa and sperm precursorsINTERNATIONAL JOURNAL OF ANDROLOGY, Issue 3 2004Michele Salemi Summary The sperm protein associated with nucleus in the X chromosome (SPANX) gene family is constituted by only a few members, clustered at Xq27, encoding small proteins which range from 15 to 20 kDa. These proteins have been shown to be present both in mature spermatozoa and in tumours, such as melanoma and some leukaemias. We developed polyclonal sera in order to study the distribution of the protein in human-ejaculated spermatozoa and their precursors. A synthetic peptide was designed from a domain common to the SPANX protein family and polyclonal sera were raised in mice. Seven healthy volunteer men with normal sperm parameters were recruited and the expression of SPANX proteins was evaluated in spermatozoa and ejaculated sperm precursors by immunocytochemistry and immunofluorescence analyses. SPANX proteins, present in a large fraction (96%) of mature spermatozoa, were localized in the sperm head (39.2%), midpiece (22.8%) or in both sites (34.4%). Spermatids also showed the presence of SPANX proteins in their cytoplasm, although a significantly higher number of spermatids were SPANX-negative compared with spermatozoa. In conclusion, SPANX proteins are expressed in an elevated percentage of spermatids and mature spermatozoa. In the latter, they are preferentially located in the sperm head. The greater number of SPANX-negative spermatids observed could relate to their easier exfoliation from the seminiferous tubules. [source] The CAG repeat polymorphism within the androgen receptor gene and maleness,INTERNATIONAL JOURNAL OF ANDROLOGY, Issue 2 2003Michael Zitzmann Summary The androgen testosterone and its metabolite dihydrotestosterone exert their effects on gene expression and thus effect maleness via the androgen receptor (AR). A diverse range of clinical conditions starting with complete androgen insensitivity has been correlated with mutations in the AR. Subtle modulations of the transcriptional activity induced by the AR have also been observed and frequently assigned to a polyglutamine stretch of variable length within the N-terminal domain of the receptor. This stretch is encoded by a variable number of CAG triplets in exon 1 of the AR gene located on the X chromosome. First observations of pathologically elongated AR CAG repeats in patients with X-linked spino-bulbar muscular atrophy showing marked hypoandrogenic traits were supplemented by partially conflicting findings of statistical significance also within the normal range of CAG repeat length: an involvement of prostate tissue, spermatogenesis, bone density, hair growth, cardiovascular risk factors and psychological factors has been demonstrated. The highly polymorphic nature of glutamine residues within the AR protein implies a subtle gradation of androgenicity among individuals within an environment of normal testosterone levels providing relevant ligand binding to ARs. This modulation of androgen effects may be small but continuously present during a man's lifetime and, hence, exerts effects that are measurable in many tissues as various degrees of androgenicity and represents a relevant effector of maleness. It remains to be elucidated whether these insights are important enough to become part of individually useful laboratory assessments. [source] L1 elements, processed pseudogenes and retrogenes in mammalian genomesIUBMB LIFE, Issue 12 2006Wenyong Ding Abstract Long interspersed nuclear elements 1 (L1 elements or LINE1) are the most active autonomous retrotransposons in mammalian genomes. In addition to L1 elements themselves, other protein-coding mRNAs can also be reverse transcribed and integrated into the genome through the L1-mediated retrotransposition, leading to the formation of processed pseudogenes (PPs) and retrogenes, both of which are characterized by the lack of introns and the presence of a 3' polyA tract and flanking direct repeats. PPs are unable to encode a functional protein and have accumulated frameshift mutations and premature stop codons during evolution. A few of PPs are transcriptionally active. Retrogenes preserve undisrupted coding frames and are capable of encoding a functional protein that is identical or nearly identical to that of the progenitor gene. There is a significant excess of retrogenes that originate from the X chromosome and are retrotransposed into autosomes, and most of these retrogenes are specially expressed in male germ cells, suggesting the inactivation of X-linked genes during male meiosis provides a strong selection pressure on retrogenes originating from the X chromosome. iubmb Life, 58: 677-685, 2006 [source] Identification of monozygous twins and microsatellite mutation rate in pigs from QTL linkage analysis dataJOURNAL OF ANIMAL BREEDING AND GENETICS, Issue 5 2001L. Grapes In previous work, microsatellite markers have primarily been tools for genome studies. However, the use of marker data can be extended beyond its original intent to maximize the amount of information obtained. There have been few studies to determine the occurrence of monozygous (MZ) twins in pigs. The advent of DNA marker technology, and microsatellites in particular, allows MZ twins to be identified based on their genotype data. To determine if MZ twin births occur in pigs, genotypes for F2 individuals, n=525, from 65 Berkshire × Yorkshire families were examined. One pair of female twins was found to have matching genotype data (95% CI: 0,2.94 twins). This is a unique result since there have been no published reports to date of twin pigs that survived until birth. Additionally, three dinucleotide microsatellite mutations were found after screening 134 565 meioses of 125 loci spanning the entire genome and the X chromosome. The average mutation rate for the population, n=570, was 2.23 × 10,5 (95% CI: 6.17 × 10,6,6.51 × 10,5). A mutation rate similar to this was published earlier for dinucleotide repeat microsatellite mutations in swine. Identification de jumeaux monozygotes et taux de mutation des microsatellites à partir de données d, analyse de liaison avec des caractères quantitatifs Jusqu'à présent, les marqueurs microsatelittes ont été principalement utilisés comme outils pour étudier le génome. Cependant, l'utilisation des données de marquage peut être étendue au delà de ce but initial et permet d'obtenir d'autres types d'informations. Au cours des dernières années, il n'y a eu que peu d'études visant à determiner l'existence de jumeaux monozygotes (MZ) chez le porc. L'avènement des techniques de marquage de l'ADN, et plus particulièrement des microsatelittes, permet l'identification de jumeaux MZ sur la base de leur génotype aux marqueurs. Afin de déterminer s'il existe des jumeaux MZ chez le porc, nous avons examiné les génotypes d'individus F2 (n=525) issus de 65 familles Berkshire × Yorkshire. La recherche d'individus ayant un genotype identique a permis d'identifer un couple de jumeaux femelles (95% CI: 0,2.94). Il s'agit d'un résultat unique car jusqu'à ce jour, il n'y avait aucun cas publié de jumeaux ayant survécus après la naissance chez le porc. Par ailleurs, après analyse de 134 565 méioses pour 125 loci répartis sur l'ensemble du génome et sur le chromosome X, 3 mutations ont été trouvées au niveau de microsatelittes dinucleotidiques. Le taux moyen de mutation dans la population (n=570) a été estiméà 2.23 × 10,5 (95% IC: 6.17 × 10,6à 6.51 × 10,5). Un taux de mutation similaire à celui-ci a été publié précédemment pour des marqueurs microsatelittes dinucleotidiques chez le porc. [source] Muscular Dystrophy in female DogsJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 3 2001G. Diane Shelton The most common form of muscular dystrophy in dogs and humans is caused by mutations in the dystrophin gene. The dystrophin gene is located on the X chromosome, and, therefore, disease-causing mutations in dystrophin occur most often in males. Therefore, females with dystrophin deficiency or other forms of muscular dystrophy may be undiagnosed or misdiagnosed. Immunohisto-chemistry was used to analyze dystrophin and a number of other muscle proteins associated with muscular dystrophy in humans, including sarcoglycans and laminin ,2, in muscle biopsy specimens from 5 female dogs with pathologic changes consistent with muscular dystrophy. The female dogs were presented with a variety of clinical signs including generalized weakness, muscle wasting, tremors, exercise intolerance, gait abnormalities, and limb deformity. Serum creatine kinase activity was variably high. One dog had no detectable dystrophin in the muscle; another was mosaic, with some fibers normal and others partly dystrophin-deficient. A 3rd dog had normal dystrophin but no detectable laminin ,2. Two dogs could not be classified. This study demonstrates the occurrence of dystrophin- and laminin ,2-associated muscular dystrophy and the difficulty in clinical diagnosis of these disorders in female dogs. [source] Characterization of novel microsatellites from Drosophila transversaMOLECULAR ECOLOGY RESOURCES, Issue 2 2009L. RÄISÄNEN Abstract We investigated a partial genomic library of Drosophila transversa for microsatellites and developed 12 markers for genetic analyses. This is the first time that microsatellite primers from the quinaria species group have been described. Four loci were cross-amplified in D. phalerata. Nine out of the 12 microsatellite markers developed are likely to be on the X chromosome. [source] Isolation of sixteen autosomal loci and a sex-linked polymorphic microsatellite locus from the Milne-Edwards' sportive lemur (Lepilemur edwardsi)MOLECULAR ECOLOGY RESOURCES, Issue 1 2009M. CRAUL Abstract We isolated 21 microsatellites from the Milne-Edwards' sportive lemur, Lepilemur edwardsi. Eighteen microsatellite sequences possessed sufficient flanking DNA for primer design. Seventeen loci amplified and were found to be polymorphic displaying two to 17 alleles in 32 unrelated individuals from a population from the National Park of Ankarafantsika in northwest Madagascar. One locus (Led-12) was found to be sex linked located on the X chromosome and can be used to sex-type 40% of female L. edwardsi lemurs. These 17 loci were characterized to investigate family structure and the phylogeography of L. edwardsi. [source] | |||||||||||||||||||||||||||||||||||||