Ontology highlight
ABSTRACT:
PROVIDER: PRJNA908831 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR22534035_1.fastq.gz | Fastqsanger.gz | |||
| SRR22534035_2.fastq.gz | Fastqsanger.gz |
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Project description:<p>The Gabriella Miller Kids First Pediatric Research Program (Kids First) is a trans-NIH effort initiated in response to the 2014 Gabriella Miller Kids First Research Act and supported by the NIH Common Fund. This program focuses on gene discovery in pediatric cancers and structural birth defects and the development of the Gabriella Miller Kids First Pediatric Data Resource (Kids First Data Resource). Both childhood cancers and structural birth defects are critical and costly conditions associated with substantial morbidity and mortality. Elucidating the underlying genetic etiology of these diseases has the potential to profoundly improve preventative measures, diagnostics, and therapeutic interventions.</p> <p>Whole Genome Sequence (WGS) and phenotypic data from this study are accessible through dbGaP and <a href="https://kidsfirstdrc.org/">kidsfirstdrc.org</a>, where other Kids First datasets can also be accessed. Disorders/Differences of Sex Development (DSD) are congenital conditions in which development of chromosomal, gonadal, or anatomic sex is atypical. DSD are chronic medical conditions collectively affecting ~1% of the population, frequently requiring life-long care by multiple specialists, and carrying a significant public health burden. Some are associated with life-threatening events, such as adrenal crises in Congenital Adrenal Hyperplasia (CAH). DSD are also associated with increased infertility, cancer, gender dysphoria risks, psychosocial distress and pervasive challenges to health-related quality of life (HRQoL) for patients and families. DSD are broadly classified into three categories: sex chromosome DSD, 46,XY DSD and 46,XX DSD, and further classified according to the type of gonad found in the patient (ovary, testis, ovotestis). </p> <p>We were able to increase significantly the diagnostic success for DSD using Whole Exome Sequencing (WES), with the identification of disease-causing and likely pathogenic variants in a third of a cohort of 46,XY patients. We have therefore proposed a shift in the diagnostic approach to DSD to use next-gen sequencing as a first-line clinical test, which could lead to faster and more accurate diagnosis, and orient further clinical management, limiting unnecessary, costly, and often invasive endocrine testing and imaging. However many remain unexplained (over half of the XY cases, a significant minority of XX cases, including most ovotesticular DSD, and most syndromic cases). In addition, the very large phenotypic variability in cases with known variants in the same gene is unexplained. </p> <p>We here propose to use Whole-Genome Sequencing (WGS), which dramatically improves upon exome sequencing, covering both coding and non-coding parts of the genome more uniformly, as an approach to not only improve diagnostic yield, but also to identify novel genes and regulatory elements involved in DSD.</p>
| phs001178 | dbGaP
Project description:Differences of Sex Development (DSD) are a set of conditions where development of chromosomal, gonadal, or anatomical sex is atypical. With overlapping phenotypes and multiple genes involved, poor diagnostic yields are achieved for many of these conditions. The current DSD diagnostic regimen can be augmented by investigating transcriptome/proteome in vivo, but it is hampered by the unavailability of affected gonadal tissue at the relevant developmental stage. We try to mitigate this limitation by reprogramming readily available skin tissue-derived dermal fibroblasts into Sertoli cells (SC), which could then be deployed for different diagnostic strategies. SCs form the target cell type of choice because they act like an organizing center of embryonic gonadal development and many DSD arise when these developmental processes go awry. Methods: We employed a computational predictive algorithm for cell conversions called Mogrify to predict the transcription factors (TFs) required for direct reprogramming of human dermal fibroblasts into SCs. We established trans-differentiation culture conditions where stable transgenic expression of these TFs was achieved in 46, XY adult dermal fibroblasts using lentiviral vectors. The resulting Sertoli like cells (SLCs) were validated for SC phenotype using several approaches. Results: SLCs exhibited Sertoli-like morphological and cellular properties as revealed by morphometry and xCelligence cell behavior assays. They also showed Sertoli-specific expression of molecular markers such as SOX9, PTGDS, BMP4, or DMRT1 as revealed by IF imaging, RNAseq and qPCR. The SLC transcriptome shared about two thirds of its differentially expressed genes with a human adult SC transcriptome and expressed markers typical of embryonic SCs. Notably, SLCs lacked expression of most markers of other gonadal cell types such as Leydig, germ, peritubular myoid or granulosa cells. Conclusions: The trans-differentiation method was applied to a variety of commercially available 46, XY fibroblasts derived from patients with DSD and to a 46, XX cell line. The DSD SLCs displayed altered levels of trans-differentiation in comparison to normal 46, XY-derived SLCs, thus showcasing the robustness of this new trans-differentiation model.
2024-03-01 | GSE246236 | GEO
Project description:We developed a cellular model to study sex differences in humans. Using somatic cells from a mosaic Kleinefelter patient, we generated isogenic human induced pluripotent stem cell lines with different sex chromosome complements – 47,XXY / 46,XX / 46,XY and 45,X0. 46, XX and 46, XY hiPSCs were differentiated to neural progenitor cells and compared.
2022-11-24 | GSE145118 | GEO
Project description:We developed a cellular model to study sex differences in humans. Using somatic cells from a mosaic Kleinefelter patient, we generated isogenic human induced pluripotent stem cell lines with different sex chromosome complements – 47,XXY / 46,XX / 46,XY and 45,X0.
2022-11-24 | GSE145079 | GEO
Project description:MIRAGE Syndrome is a Rare Cause of 46,XY DSD Born SGA without Adrenal Insufficiency
| PRJDB7544 | ENA
Project description:Somatic genetic copy number analysis of bone marrow from a male patient with refractory cytopenia with multilineage dysplasia and ringed sideroblasts and an abnormal karyotype, 45,XY,der(5)t(5;14)(q14;?q24),dic(17;20)(p13;q12),dic(17;20)(p11.2;q12),-18,+22[6]/45,XY,der(5)t(5;14)(q14;?q24),dic(17;20)(20pter->20p11.2::17p1?1.2->17p1?3::20q12->20q10::20q10->20q12::17p11.2->17qter),dic(17;20)(p11.2;q11.2),-18,+22[cp2]/46,XY,der(5)t(5;14)(q14;?q24),der(17)(20pter->20p13::20q11.2->20q11.2::17p13->17qter),der(17)(20pter->20p11.2::20q11.2->20q11.2::17p13->17qter),-18, 20,+22,+r[9] (Case 6, MacKinnon et al 2007, Genes Chr Cancer 46:27-36)
2010-01-09 | E-MEXP-2275 | biostudies-arrayexpress
Project description:This gene set contains skin fibroblasts from either labia majora of 46,XY sex reversed females having complete androgen insensitivity syndrome due to inactivation mutations of the androgen receptor gene and from the scrotum of normal males. Both, labia majora and scrotum origin from the same embryological anlagen, the labioscrotal swellings. The phenotypic difference is due to androgen dependent virilization in males. This is not possible in 46,XY patients with complete androgen insensitivity syndrome because the androgen receptor pathway is knocked out. A cell type comparison design experiment design type compares cells of different type for example different cell lines. Cell Line: genital skin fibroblasts from different locations mutant line: normal 46,XY male and 46,XY sex reversed female due to inactivating mutations of the androgen receptor gene Keywords: cell_type_comparison_design
2007-10-20 | GSE6797 | GEO
Project description:This gene set contains skin fibroblasts from either labia majora of 46,XY sex reversed females having complete androgen insensitivity syndrome due to inactivation mutations of the androgen receptor gene and from the scrotum of normal males. Both, labia majora and scrotum origin from the same embryological anlagen, the labioscrotal swellings. The phenotypic difference is due to androgen dependent virilization in males. This is not possible in 46,XY patients with complete androgen insensitivity syndrome because the androgen receptor pathway is knocked out. A cell type comparison design experiment design type compares cells of different type for example different cell lines. Cell Line: genital skin fibroblasts from different locations mutant line: normal 46,XY male and 46,XY sex reversed female due to inactivating mutations of the androgen receptor gene Computed
2010-06-25 | E-GEOD-6797 | biostudies-arrayexpress
Project description:Detection of genomic rearrangements from a single cell instead of a population of cells is an emerging research technique with important applications in the study of human fertility, constitutional chromosomal disorders, and tumor progression. Here, we develop a method to improve the detection of single-cell genome-wide copy number variation. At this study, 7 amplified single cell DNA samples derived from EBV-line [47,XY,+21], [46,XY,der(20),t(18;20)(p11.21;p13)], [46,XX,del(18)(p11.21->pter)], [46,X,der(X),t(X;14)(q21.1;q12.2)] were analyzed by Agilent 244K array CGH. For these single cell Agilent 244K array CGH analyses: non-amplified genomic DNA extracted from the blood of a Klinefelter patient (XXY) was used as a reference sample. As a validation, the corresponding non-amplified genomic DNA samples were analyzed by 250K Nsp I SNP arrays (platform GPL3718). Non-amplified genomic DNA extracted from the blood of a Klinefelter patient (XXY) was used as a reference sample for BAC array CGH
2011-08-23 | E-GEOD-27892 | biostudies-arrayexpress