Gene Expression Study of Individuals with Sex Chromosome Aneuploidies
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PROVIDER: PRJNA741694 | ENA |
REPOSITORIES: ENA
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Project description:Gene Expression Study of Individuals with Sex Chromosome Aneuploidies
| PRJNA741693 | ENA
Project description:Induced pluripotent stem cells (iPSCs) offer opportunity for insight into the genetic requirements of the X chromosome for somatic and germline development. Turner syndrome is caused by complete or partial loss of the second sex chromosome; while more than 90% of Turner cases result in spontaneous fetal loss, survivors display an array of somatic and germline clinical characteristics. Here, we derived iPSCs from Turner syndrome and control individuals and examined germ cell development as a function of X chromosome composition. We analyzed gene expression profiles of derived iPSCs and in vitro differentiated cells by single cell qRT-PCR and RNA-seq. We whoed that two X chromosomes are not necessary for reprogramming or pluripotency maintenance. Genes that escape X chromosome inactivation (XCI) between control iPSCs and those with X chromosome aneuploidies revealed minimal expression differences relative to a female hESC line. Moreover, when we induced germ cell differentiation via murine xenotransplantation of iPSC lines into the seminiferous tubules of busulfan-treated mice, we observed that undifferentiated iPSCs, independent of X chromosome composition, when placed within the correct somatic environment, are capable of forming early germ cells in vivo. Results indicate that two intact X chromosomes are not required for germ cell formation; however, clinical data suggest that two sex chromosomes are required for maintenance of human germ cells. RNA-seq of H9 cells, iPSCs from Turner syndrome and control individuals and in vitro differentiated cells
2015-05-18 | E-GEOD-55939 | biostudies-arrayexpress
Project description:Induced pluripotent stem cells (iPSCs) offer opportunity for insight into the genetic requirements of the X chromosome for somatic and germline development. Turner syndrome is caused by complete or partial loss of the second sex chromosome; while more than 90% of Turner cases result in spontaneous fetal loss, survivors display an array of somatic and germline clinical characteristics. Here, we derived iPSCs from Turner syndrome and control individuals and examined germ cell development as a function of X chromosome composition. We analyzed gene expression profiles of derived iPSCs and in vitro differentiated cells by single cell qRT-PCR and RNA-seq. We whoed that two X chromosomes are not necessary for reprogramming or pluripotency maintenance. Genes that escape X chromosome inactivation (XCI) between control iPSCs and those with X chromosome aneuploidies revealed minimal expression differences relative to a female hESC line. Moreover, when we induced germ cell differentiation via murine xenotransplantation of iPSC lines into the seminiferous tubules of busulfan-treated mice, we observed that undifferentiated iPSCs, independent of X chromosome composition, when placed within the correct somatic environment, are capable of forming early germ cells in vivo. Results indicate that two intact X chromosomes are not required for germ cell formation; however, clinical data suggest that two sex chromosomes are required for maintenance of human germ cells.
2015-05-18 | GSE55939 | GEO
Project description:Purpose
The landscape of circular RNAs (circRNAs), an important class of non-coding RNAs that regulate gene expression, has never been described in human disorders of sex chromosome aneuploidies. We profiled circRNAs in Turner syndrome females (45,X;TS) and Klinefelter syndrome males (47,XXY; KS) to investigate how circRNAs respond to a missing or an extra X chromosome.
Methods
Samples of blood, muscle and fat were collected from individuals with TS (n = 33) and KS (n = 22) and from male (n = 16) and female (n = 44) controls. CircRNAs were identified using a combination of circRNA identification pipelines (CIRI2, CIRCexplorer2 and circRNA_finder).
Results
Differential expression of circRNAs was observed throughout the genome in TS and KS, in all tissues. The host-genes from which several of these circRNAs were derived, were associated with known phenotypic traits. Furthermore, several differentially expressed circRNAs had the potential to capture micro RNAs that targeted protein-coding genes with altered expression in TS and KS.
Conclusion
Sex chromosome aneuploidies introduce pervasive changes in the circRNA transcriptome, demonstrating that the genomic changes in these syndromes are more complex than hitherto thought. CircRNAs may help explain some of the genomic and phenotypic traits observed in these syndromes.
| EGAS00001006404 | EGA
Project description:Whole Y-chromosome sequences from Argentine individuals
| PRJEB47808 | ENA
Project description:BackgroundSupernumerary sex chromosome aneuploidies (SCA) are common genetic conditions characterized by additional X or Y chromosome, affecting ~1/500 individuals, with the most frequent karyotypes of 47,XXY (Klinefelter syndrome), 47,XXX (Trisomy X), and 47,XYY (Jacob syndrome). Although there is considerable phenotypic variation among these diagnoses, these conditions are characterized by the presence of overlapping physical, medical, developmental, and psychological features. Our interdisciplinary clinic's experience anecdotally supports previous published findings of atopic conditions, feeding difficulties, and gastroesophageal reflux to be more prevalent in SCAs (Bardsley et al., Journal of Pediatrics, 2013, 163, 1085; Samango-Sprouse et al., The Application of Clinical Genetics, 2019, 12, 191; Tartaglia et al., Acta Paediatrica, 2008, 100, 851). Furthermore, we observed that many of these patients have also been diagnosed with eosinophilic esophagitis (EoE), an association not currently reported in the literature.MethodsWe conducted a retrospective chart review of all 667 patients with SCA seen at a large tertiary care center to investigate the prevalence and presenting features of EoE.ResultsFour percent of children with SCAs had a biopsy-confirmed diagnosis of EoE, which represents an odds ratio of 32 (95% CI 6-185) when compared to the prevalence rates reported in the general population.ConclusionRoutine screening for EoE symptoms may be warranted for individuals with SCA and atopic conditions.
| S-EPMC8683639 | biostudies-literature
Project description:Targeted assembly of ectopic kinetochores to induce chromosome-specific segmental aneuploidies
| PRJEB59859 | ENA
Project description:Aneuploidy and chromosomal instability are both commonly found in cancer. Chromosomal instability leads to karyotype heterogeneity in tumors and is associated with therapy resistance, metastasis and poor prognosis. It has been hypothesized that aneuploidy per se is sufficient to drive CIN, however due to limited models and heterogenous results, it has remained controversial which aspects of aneuploidy can drive CIN. In this study we systematically tested the impact of different types of aneuploidies on the induction of CIN. We generated a plethora of isogenic aneuploid clones harboring whole chromosome or segmental aneuploidies in human p53-deficient RPE-1 cells. We observed increased segregation errors in cells harboring trisomies that strongly correlated to the number of gained genes. Strikingly, we found that clones harboring only monosomies do not induce a CIN phenotype. Finally, we found that an initial chromosome breakage event and subsequent fusion can instigate breakage-fusion-bridge cycles. By investigating the impact of monosomies, trisomies and segmental aneuploidies on chromosomal instability we further deciphered the complex relationship between aneuploidy and CIN.
2022-06-14 | GSE193437 | GEO
Project description:The difference in X chromosome copy number creates a potential difference in X chromosomal gene expression between males and females. In many animals, dosage compensation mechanisms equalize X chromosome expression between sexes. Yet, X chromosome is also enriched for sex-biased genes due to differences in the evolutionary history of the X and autosomes. The manner in which dosage compensation and sex-biased gene expression exist on the X chromosome remains an open question. Most studies compare gene expression between two sexes, which combines expression differences due to X chromosome number (dose) and sex. Here, we uncoupled the effects of sex and X dose in C. elegans and determined how each process affects expression of the X chromosome compared to autosomes. We found that in the soma, sex-biased expression on the X chromosome is almost entirely due to sex because the dosage compensation complex (DCC) effectively compensates for the X dose difference between sexes. In the germline where the DCC is not present, X chromosome copy number contributes to hermaphrodite-biased gene expression. These results suggest that X dose contributes to sex-biased gene expression based on the level of dosage compensation in different tissues and developmental stages.
2016-04-06 | GSE77794 | GEO
Project description:It is well recognized that men and women differ in circulating lipid profiles and consequently coronary artery disease (CAD). While sex hormones like estrogens are thought to protect women from CAD risk by promoting protective lipid profiles, hormone replacement therapy in women paradoxically increases CAD risk. Biological sex is determined by both sex chromosomes and sex hormones. We used mouse models to separate effects of sex chromosomes and hormones on atherosclerosis, circulating lipids and intestinal fat metabolism. We found that an XX sex chromosome complement increases food intake, body weight, fat absorption, serum lipid concentrations and atherosclerosis in gonadal male and female mice, indicating a primary effect of sex chromosome complement. Small intestine expression of enzymes involved in lipid absorption and chylomicron assembly were increased in XX male and female mice with elevated intestinal lipids. These results reveal that an XX sex chromosome complement promotes the absorption and bioavailability of dietary fat to accelerate the development of atherosclerosis.
2019-04-17 | GSE119497 | GEO