Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA253497 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Kallmann syndrome is a genetically heterogeneous condition and a treatable form of male infertility. Defects in KAL1 gene have been implicated in Kallmann syndrome, which can be associated with X-linked ichthyosis in contiguous gene syndromes. In order to uncover the genetic cause of two brothers with Kallmann syndrome and X-linked ichthyosis, a custom semiconductor targeted resequencing panel to detect seventeen Kallmann syndrome causal genes and STS gene was designed. Next-generation sequencing was performed using this panel in the two affected brothers and their normal parents. To validate the result, we applied CytoScan⢠HD array, quantitative real-time PCR and direct PCR electrophoresis analysis with the participants. The patients received clinical assessment, human chorionic gonadotropin treatment and follow-up for 39 months. The results showed that the two affected siblings have the same de novo deletion at Xp22.3 including exons 9-14 of KAL1 gene and entire STS gene but showed different phenotypes in some respects. The secondary sex characteristics of the patients were greatly improved after treatment. We firstly reported that a de novo homozygous deletion contribute to KS with bilateral cryptorchidism and unilateral renal agenesis or normal kidney development and developed a cost-effective and reliable semiconductor targeted resequencing panel for genetic diagnosis of Kallmann syndrome in routinely obtained samples. One of the two brothers with Kallmann syndrome and X-linked ichthyosis was analyzed for validation the results of the deletion detected by next-generation sequencing.
2015-12-05 | E-GEOD-58793 | biostudies-arrayexpress
Project description:Kallmann syndrome is a genetically heterogeneous condition and a treatable form of male infertility. Defects in KAL1 gene have been implicated in Kallmann syndrome, which can be associated with X-linked ichthyosis in contiguous gene syndromes. In order to uncover the genetic cause of two brothers with Kallmann syndrome and X-linked ichthyosis, a custom semiconductor targeted resequencing panel to detect seventeen Kallmann syndrome causal genes and STS gene was designed. Next-generation sequencing was performed using this panel in the two affected brothers and their normal parents. To validate the result, we applied CytoScan™ HD array, quantitative real-time PCR and direct PCR electrophoresis analysis with the participants. The patients received clinical assessment, human chorionic gonadotropin treatment and follow-up for 39 months. The results showed that the two affected siblings have the same de novo deletion at Xp22.3 including exons 9-14 of KAL1 gene and entire STS gene but showed different phenotypes in some respects. The secondary sex characteristics of the patients were greatly improved after treatment. We firstly reported that a de novo homozygous deletion contribute to KS with bilateral cryptorchidism and unilateral renal agenesis or normal kidney development and developed a cost-effective and reliable semiconductor targeted resequencing panel for genetic diagnosis of Kallmann syndrome in routinely obtained samples.
2015-12-05 | GSE58793 | GEO
Project description:Recessive X-linked ichthyosis (RXLI), a genetic disorder caused by deletion or point mutations of the steroid sulfatase (STS) gene, is the second most common form of ichthyosis. It is a disorder of keratinocyte cholesterol sulphate retention and the mechanism of extracutaneous phenotypes such as corneal opacities and attention deficit hyperactivity disorder are poorly understood. To understand the pathomechanisms of RXLI, the transcriptome of differentiated primary keratinocytes with STS knockdown was sequenced. The results were validated at the protein level in a stable knockdown model of STS, to confirm STS specificity, and in RXLI skin. The results show that there was significantly reduced expression of genes related to epidermal differentiation and lipid metabolism, including ceramide and sphingolipid synthesis. In addition, there was significant downregulation of aldehyde dehydrogenase family members and the oxytocin receptor which have been linked to corneal transparency and behavioural disorders respectively, both of which are extracutaneous phenotypes of RXLI. These data provide a greater understanding of the causative mechanisms of RXLI’s cutaneous phenotype, and show that the keratinocyte transcriptome and lipidomics can give novel insights into the phenotype of patients with RXLI.
2023-05-30 | GSE232622 | GEO
Project description:Autosomal recessive congenital ichthyoses are a group of non-syndromic congenital keratinization disorders including harlequin ichthyosis, lamellar ichthyosis, and congenital ichthyosiform erythroderma with a total prevalence of 1:200,000. Affected individuals who are often born as collodion babies present with generalized scaling of the skin. This reflects a physical compensation for the defective cutaneous permeability barrier underlying all ichthyoses. Inactivity of 12R-lipoxygenase (12R-LOX) is a frequent cause of ARCI. Mice with targeted inactivation of the 12R-LOX gene Alox12b were established .Heterozygous mutant mice (Alox12b+/−) were bred with 129S6, and their heterozygous offspring were intercrossed to obtain homozygous mutant mice. Homozygous Alox12b knockout mice died within 3 hours after birth owing to defective skin barrier function. We used microarray to compare the gene expression profile in the epidermis of Alox12b-null mice with that of wildtype animals. Inactivation of Alox12b was associated with the upregulation of genes involved in keratinization, cholesterol biosynthesis, and Fc-epsilon receptor signaling.
2019-03-01 | GSE127435 | GEO
Project description:Relapse is the commonest cause of death in acute myeloid leukaemia (AML), but the mechanisms leading to relapse are unclear. Recently, acquisition of segmental uniparental disomy (UPD) by mitotic recombination (MR) has been reported in 15-20% of AML samples at diagnosis using whole genome single nucleotide polymorphism (SNP) arrays. These cytogenetically invisible abnormalities are associated with homozygous mutations in several types of malignancy. Clonal evolution of heterozygous to homozygous mutations by MR could provide a mechanism for relapse. Keywords: DNA copy number, loss of heterozygosity
2008-05-01 | GSE7210 | GEO
Project description:Juvenile hemochromatosis type 2A in the studied patient was caused by a homozygous mutation c.196G>T (p.G66*) in hemojuvelin. Homozygous state for this mutation evolved through interstitial segmental isodisomy encompassing the centromeric region of chromosome 1 accompanying its paternal disomy. The disomy resulted into normal karyotype SNP genotyping was performed on 3 samples - family trio. Affymetrix GeneChip Command Console software was used for image processing and CEL files were processed by Affymetrix GTC using the BRLMM-P-Plus algorithm and regional GC correction configuration for Copy Number/LOH analysis. The HapMap270 file supplied by Affymetrix was used as the reference.
2014-01-30 | E-GEOD-50441 | biostudies-arrayexpress
Project description:The cause of mental retardation in one-third to one-half of all affected individuals is unknown. Microscopically-detectable chromosomal abnormalities are the most frequent recognized cause, but gain or loss of chromosomal segments that are too small to be seen by conventional cytogenetic analysis has been found to be another important cause. Array-based methods offer a practical means of performing a high-resolution survey of the entire genome for submicroscopic copy number variants. We studied 100 children with idiopathic mental retardation and their parents using the Affymetrix GeneChip® Mapping 100K Assay and found de novo duplications as small as 1.1 Mb in three cases, de novo deletions as small as 178 kb in eight cases, and unsuspected mosaic trisomy 9 in another case. This technology can detect at least twice as many potentially pathogenic de novo copy number variants as conventional cytogenetic analysis in people with mental retardation. Experiment Overall Design: Using the Affymetrix GeneChip® Mapping 100K Assay we studied 100 trios that each included one child with idiopathic mental retardation (MR) and both of his/her unaffected biological parents. We also tested 10 unaffected siblings of the MR children from 10 of the above families. In addition, we analyzed 7 trios (child and both unaffected biological parents) as positive controls with previously identified chromosomal aberrations. Experiment Overall Design: Within each sample ID the four digit number refers to a family. Following this four digit family number, 'c' indicates child with MR, 'm' means unaffected mother, 'f' means unaffected father and 's' means unaffected sibling.
2008-06-21 | E-GEOD-7226 | biostudies-arrayexpress
Project description:Relapse is the commonest cause of death in acute myeloid leukaemia (AML), but the mechanisms leading to relapse are unclear. Recently, acquisition of segmental uniparental disomy (UPD) by mitotic recombination (MR) has been reported in 15-20% of AML samples at diagnosis using whole genome single nucleotide polymorphism (SNP) arrays. These cytogenetically invisible abnormalities are associated with homozygous mutations in several types of malignancy. Clonal evolution of heterozygous to homozygous mutations by MR could provide a mechanism for relapse. Experiment Overall Design: DNA from 27 pairs of diagnostic and relapsed AML samples were analysed using Affymetrix 10K SNP arrays. The genotype data of relapsed AML were compared with the data from the corresponding presentation AML.
2008-06-15 | E-GEOD-7210 | biostudies-arrayexpress
Project description:Vibrio harveyi is a major bacterial pathogen that can cause fatal vibriosis in Chinese tongue sole (Cynoglossus semilaevis). To comprehend the molecular mechanisms of C. semilaevis host response against V. harveyi infection, we performed transcriptome (RNA-seq) analysis of C. semilaevis from resistant family and susceptible family.
2019-02-26 | GSE126995 | GEO