Human PI3Kγ Deficiency with Immunodeficiency and Tissue Immunopathology
Ontology highlight
ABSTRACT: Whole exome sequencing of a trio (parents and offspring) reveals PIK3CG mutations that result in loss of protein in the child with immunodeficiency and immunopathology.
REPOSITORIES: dbGaP
Dataset's files
Items per page: 5 1 - 5 of 17 |
Similar Datasets
Project description:Whole exome sequencing (WES) files of a patient suffering from a combined immunodeficiency, and his parents.
2014-10-31 | E-MTAB-2962 | biostudies-arrayexpress
Project description:Heterosis occurs where F1 offspring display superior characteristics to the parents. Heterosis is usually considered to result from crosses of genetically distinct (e.g. homozygous inbred) parents producing heterozygous F1 offspring. Most mechanistic models for heterosis require genetically heterozygous F1 hybrid offspring harbouring allelic diversity. Epigenetic or dosage models for heterosis could allow for heterosis effects in F1 offspring that display no allelic diversity with their parents. Reciprocal inter-ploidy crosses between diploid (2x) and tetraploid (4x) lines in the same genetic background generates genetically identical F1 triploids (3x). Such reciprocal F1 triploids differ according to whether the additional chromosome set is either maternally (maternal excess) or paternally inherited (paternal excess). Biomass accumulation and abiotic stress tolerance between the parental (2x and 4x) and reciprocal F1 triploid (3x) offspring of Arabidopsis thaliana accession C24 reveals a strong parental genome-dosage induced heterosis in the paternal-excess triploid F1 plants. In these F1 triploids, the circadian clock related genes CCA1 and TOC1, and the growth factors PIF4 and PIF5, display different expression levels compared to the non-heterotic maternal excess F1 triploid siblings. Whole transcriptome profiling reveals a paternal genome dosage effect on gene expression levels with strong enrichment for dysregulated abiotic stress-related genes in the paternal excess F1 triploids. This study demonstrates that heterosis can be triggered without allelic diversity in F1 triploid plants. Heterosis without heterozygosity in plants can be induced via an epigenetic “chromosome imprinting” like parental genome dosage effect requiring paternal transmission of an additional chromosome set 4 or 5 biological replicates per ploidy level, each replicate being a single two weeks old seedling
2014-08-01 | E-GEOD-52885 | biostudies-arrayexpress
Project description:Chromothripsis represents an extreme class of complex chromosome rearrangements (CCRs) with major effects on chromosomal architecture. Although recent studies have associated chromothripsis with congenital abnormalities, the incidence and pathogenic effects of this phenomenon require further investigation. Here, we analyzed the genomes of three families in which chromothripsis rearrangements were transmitted from a mother to her child. The chromothripsis in the mothers resulted in completely balanced rearrangements involving 8-23 breakpoint junctions across 3-5 chromosomes. Two mothers did not show any phenotypic malformations, although 3-13 protein coding genes were affected by breakpoints. Unbalanced but stable transmission of a subset of the derivative chromosomes caused apparently de novo complex copy number changes in two children. This resulted in gene dosage changes, which are likely responsible for their severe congenital phenotypes. In contrast, one child with severe congenital disease, carried all three chromothripsis chromosomes from his healthy mother, but one of the chromosomes acquired de novo rearrangements leading to copy number changes. These results show that the human genome can tolerate extreme reshuffling of chromosomal architecture, including breakage of multiple protein coding genes, without noticeable phenotypic effects. The presence of chromothripsis in healthy individuals strongly affects reproduction and is expected to substantially increase the risk of spontaneous abortions and severe congenital disease. We analyzed one patient-parent-mother's parents quintet (case 1) and a patient-siblings-parent quintet (case 2) with Illumina beadchip arrays and one patient-parent trio (case 3) to test for (de novo) copy number variants and to analyze the parental origin of the complex rearrangements in these patients. This study represents one child-parent trio (case 3) test for (de novo) copy number variants in the child.
2015-01-31 | E-GEOD-65453 | biostudies-arrayexpress
Project description:Heterosis occurs where F1 offspring display superior characteristics to the parents. Heterosis is usually considered to result from crosses of genetically distinct (e.g. homozygous inbred) parents producing heterozygous F1 offspring. Most mechanistic models for heterosis require genetically heterozygous F1 hybrid offspring harbouring allelic diversity. Epigenetic or dosage models for heterosis could allow for heterosis effects in F1 offspring that display no allelic diversity with their parents. Reciprocal inter-ploidy crosses between diploid (2x) and tetraploid (4x) lines in the same genetic background generates genetically identical F1 triploids (3x). Such reciprocal F1 triploids differ according to whether the additional chromosome set is either maternally (maternal excess) or paternally inherited (paternal excess). Biomass accumulation and abiotic stress tolerance between the parental (2x and 4x) and reciprocal F1 triploid (3x) offspring of Arabidopsis thaliana accession C24 reveals a strong parental genome-dosage induced heterosis in the paternal-excess triploid F1 plants. In these F1 triploids, the circadian clock related genes CCA1 and TOC1, and the growth factors PIF4 and PIF5, display different expression levels compared to the non-heterotic maternal excess F1 triploid siblings. Whole transcriptome profiling reveals a paternal genome dosage effect on gene expression levels with strong enrichment for dysregulated abiotic stress-related genes in the paternal excess F1 triploids. This study demonstrates that heterosis can be triggered without allelic diversity in F1 triploid plants. Heterosis without heterozygosity in plants can be induced via an epigenetic “chromosome imprinting” like parental genome dosage effect requiring paternal transmission of an additional chromosome set
2014-08-01 | GSE52885 | GEO
Project description:Human PI3KGamma deficiency with immunodeficiency and tissue immunopathology
| PRJNA548604 | ENA
Project description:Human PI3KGamma deficiency with immunodeficiency and tissue immunopathology
| PRJNA548603 | ENA
Project description:Whole exome paired-end sequencing data was performed on a trio (patient + parents) who has primary immunodeficiency to identify the genetic cause of the immunodeficiency. Analysis revealed a novel homozygous mutation in IL2RB.
| EGAD00001004963 | EGA
Project description:Various inborn errors of the canonical NF-kB pathway underlie different forms of human immunodeficiency. However, no patients with autosomal recessive complete deficiencies of RelA, c-REL, or NF-kB1, the three core members of the canonical NF-kB pathway, have yet been identified. We report a child homozygous for a loss-of-expression mutation of REL, encoding c-REL, which is expressed principally in myeloid and lymphoid cells. The distribution of myeloid subsets is normal in this patient, but in vitro-derived monocytes and cDC1s, unlike cDC2s, have impaired IL-12 and IL-23 production. The patient has low frequencies of memory CD4+ T cells, Th1*, Th2, Tregs, and almost no memory B cells. The frequencies of the other lymphoid subsets are normal. The patient’s naïve and memory CD4+ T cells produce only small amounts of IL-2, and the addition of this interleukin rescues their proliferation in response to mitogens, but not to antigens, in vitro. However, we found that HLA-syngeneic control cDCs rescued the proliferation of these cells in response to recall antigens. The production of key effector cytokines, such as IL-4, IL-17A, and IFNg, by memory CD4+ T cells was also highly impaired ex vivo, as was the differentiation of naïve CD4+ T cells into Th1 and Th17 cells in vitro. Both the survival and proliferation of the patient’s naïve B cells were found to be compromised, preventing B-cell differentiation into immunoglobulin (Ig)-secreting plasmablasts in vitro. As a consequence of this pleiotropic effect, this child suffered from severe viral, mycobacterial, fungal, and parasitic infections, while IgG substitution treatment prevented pyogenic infections. The immunological and infectious phenotypes were of hematopoietic origin, as they were cured by hematopoietic stem cell transplantation. Inherited human c-REL deficiency impairs multiple core functions of DCs, T cells, and B cells, thereby disrupting adaptive immunity to multiple infections.
2021-08-31 | GSE167185 | GEO
Project description:Chromothripsis represents an extreme class of complex chromosome rearrangements (CCRs) with major effects on chromosomal architecture. Although recent studies have associated chromothripsis with congenital abnormalities, the incidence and pathogenic effects of this phenomenon require further investigation. Here, we analyzed the genomes of three families in which chromothripsis rearrangements were transmitted from a mother to her child. The chromothripsis in the mothers resulted in completely balanced rearrangements involving 8-23 breakpoint junctions across 3-5 chromosomes. Two mothers did not show any phenotypic malformations, although 3-13 protein coding genes were affected by breakpoints. Unbalanced but stable transmission of a subset of the derivative chromosomes caused apparently de novo complex copy number changes in two children. This resulted in gene dosage changes, which are likely responsible for their severe congenital phenotypes. In contrast, one child with severe congenital disease, carried all three chromothripsis chromosomes from his healthy mother, but one of the chromosomes acquired de novo rearrangements leading to copy number changes. These results show that the human genome can tolerate extreme reshuffling of chromosomal architecture, including breakage of multiple protein coding genes, without noticeable phenotypic effects. The presence of chromothripsis in healthy individuals strongly affects reproduction and is expected to substantially increase the risk of spontaneous abortions and severe congenital disease. We analyzed one patient-parent-mother's parents quintet (case 1) and a patient-siblings-parent quintet (case 2) with Illumina beadchip arrays and one patient-parent trio (case 3) to test for (de novo) copy number variants and to analyze the parental origin of the complex rearrangements in these patients. Here, we analyzed one patient-parent-mother's parents quintet to test for (de novo) copy number variants and to analyze the parental origin of the complex rearrangements in these patients.
2015-01-31 | E-GEOD-65451 | 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