Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA276263 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Approximately 70% of women suffering with familial recurrent moles (RHM) are associated with recessive mutations of NLRP7, which cause the RHM by maternal-effect. It has been proposed that the phenotypes of molar pregnancies are associated with aberrant genomic imprinting. Using the Illumina Infinium HumanMethylation450 Beadchip arrays we characterize the genome-wide methylation profile of 4 molar samples and blood from the female patients. We confirm widespread loss-of-imprinting in the RHM samples but not in the blood-derived DNA from the asymptomatic female patients. The aberrant methylation at imprinted loci was confirmed using bisulphite PCR and subcloning or pyrosequencing. Finally, by comparing the methylation patterns observed in the RHM with normal placenta biopsies we identify many candidate maternally methylated regions, consistent with novel imprinted genes.
2016-02-01 | GSE66247 | GEO
Project description:Analysis of the molecular etiologies of severe combined immunodeficiency (SCID) has led to important insights into the control of immune cell development. Most cases of SCID result from either X-linked or autosomal recessive inheritance of mutations in a known causative gene. However, in some cases, the molecular etiology remains unclear. To identify the cause of SCID in a patient known to lack the protein tyrosine phosphatase CD45, we utilized single nucleotide polymorphisms (SNP) Cytogenetics arrays; The patient’s mother was heterozygous for an inactivating mutation in CD45, while the paternal alleles exhibited no detectable mutations. The patient exhibited a single CD45 mutation identical to the maternal allele. Patient SNP array analysis revealed no change in copy number but loss of heterozygosity for the entire length of chromosome 1 (Chr1), indicating that disease was caused by uniparental disomy (UPD) with isodisomy of the entire maternal Chr1 bearing the mutant CD45 allele. Non-lymphoid blood cells and other mesoderm and ectoderm-derived tissues retained UPD of the entire maternal Chr1 in this patient who had undergone successful bone marrow transplantation. These findings represent the first reported case of SCID caused by UPD and suggest UPD should be considered in SCID and other recessive disorders, especially when the patient appears homozygous for an abnormal gene found in only one parent. Evaluation for alterations in other genes affected by UPD should also be considered in such cases. Affymetrix SNP Cytogenetics arrays were performed according to the manufacturer's directions on DNA extracted from cryopreserved sorted PMBC and buccal samples. Copy number and allele analysis of Affymetrix Cytogenetics arrays was performed for the patient's and his parent's samples.
2012-02-10 | E-GEOD-35674 | biostudies-arrayexpress
Project description:Maternal-effect mutations in components of the subcortical maternal complex (SCMC) of the human oocyte can cause early embryonic failure, gestational abnormalities and recurrent pregnancy loss. Enigmatically, they are also associated with DNA methylation abnormalities at imprinted genes in conceptuses, in the devastating gestational abnormality biparental complete hydatidiform mole (BiCHM) or in multi-locus imprinting disease (MLID). However, the developmental timing, genomic extent and mechanistic basis of these imprinting defects are unknown. Here, we studied methylation level of a women reported with familial recurrent hydatidiform mole and multiple pregnancy loss. Genotype analysis revealed homozygous mutation in KHDC3L. We obtained biparental mole from patient (Patient D) and compared it’s whole-genome methylation profile with respect to control placentas and sporadic mole (AnCHM) using Infinium MethylationEPIC BeadChip (WG-317-1001, Illumina). We also used endometrium samples from their respective mother for the comparison purposes. Molar conceptuses were observed with methylation defects at genome-wide level and profound loss of methylation at multiple genome-derived differentially methylated regions (gDMRs) confirming MLID.
2019-11-21 | GSE138864 | GEO
Project description:<p>Analysis of the molecular etiologies of severe combined immunodeficiency (SCID) has led to important insights into the control of immune cell development. Most cases of SCID result from either X-linked or autosomal recessive inheritance of mutations in a known causative gene. However, in some cases, the molecular etiology remains unclear. To identify the cause of SCID in a patient known to lack the protein tyrosine phosphatase CD45, we utilized single nucleotide polymorphisms (SNP) arrays and whole exome sequencing. The patient's mother was heterozygous for an inactivating mutation in <i>CD45</i>, while the paternal alleles lacked mutations. The patient exhibited a single <i>CD45</i> mutation identical to the maternal allele. Patient SNP array analysis revealed no change in copy number but loss of heterozygosity for the entire length of chromosome 1 (Chr1), indicating that disease was caused by uniparental disomy (UPD) with isodisomy of the entire maternal Chr1 bearing the <i>CD45</i> mutation. Non-lymphoid blood cells and other mesoderm and ectoderm-derived tissues retained UPD of the entire maternal Chr1 in this patient who had undergone successful bone marrow transplantation. Exome sequencing revealed mutations in 7 additional genes bearing nonsynonymous SNPs predicted to have deleterious effects. These findings represent the first reported case of SCID caused by UPD and suggest UPD should be considered in SCID and other recessive disorders, especially when the patient appears homozygous for an abnormal gene found in only one parent. Evaluation for alterations in other genes affected by UPD should also be considered in such cases.</p>
| phs000479 | dbGaP
Project description:Analysis of the molecular etiologies of severe combined immunodeficiency (SCID) has led to important insights into the control of immune cell development. Most cases of SCID result from either X-linked or autosomal recessive inheritance of mutations in a known causative gene. However, in some cases, the molecular etiology remains unclear. To identify the cause of SCID in a patient known to lack the protein tyrosine phosphatase CD45, we utilized single nucleotide polymorphisms (SNP) Cytogenetics arrays; The patient’s mother was heterozygous for an inactivating mutation in CD45, while the paternal alleles exhibited no detectable mutations. The patient exhibited a single CD45 mutation identical to the maternal allele. Patient SNP array analysis revealed no change in copy number but loss of heterozygosity for the entire length of chromosome 1 (Chr1), indicating that disease was caused by uniparental disomy (UPD) with isodisomy of the entire maternal Chr1 bearing the mutant CD45 allele. Non-lymphoid blood cells and other mesoderm and ectoderm-derived tissues retained UPD of the entire maternal Chr1 in this patient who had undergone successful bone marrow transplantation. These findings represent the first reported case of SCID caused by UPD and suggest UPD should be considered in SCID and other recessive disorders, especially when the patient appears homozygous for an abnormal gene found in only one parent. Evaluation for alterations in other genes affected by UPD should also be considered in such cases.
2012-02-10 | GSE35674 | GEO
Project description:Aims: Epidemiological and animal studies have shown that maternal diet can influence metabolism in adult offspring. However, the molecular mechanisms underlying these changes remain poorly understood. Here, we aim to explore phenotypes induced by maternal obesity in a mouse model and examine gene expression and epigenetic alterations in adulthood induced by maternal diet. Methods: We analyzed genetically identical male mice born from dams fed a high- or low-fat diet throughout pregnancy and until day 21 postpartum. After weaning, half of the males of each group were fed a high-fat diet, the other half a low-fat diet. We first characterized the genome-wide gene expression patterns of six tissues of adult offspring - liver, pancreas, white adipose, brain, muscle and heart [GSE40903] . We then measured DNA methylation patterns in liver at selected loci and throughout the genome. Results: Maternal diet had a significant effect on the body weight of the offspring when they are fed an obesogenic diet after weaning. Our analyses showed that maternal diet had a pervasive effect on gene expression, with a pronounced effect in liver where it affected many genes involved in inflammation, cholesterol synthesis and RXR activation. Maternal diet had no detectable effect on DNA methylation in the liver. Conclusions: Overall, our findings highlighted the persistent influence of maternal diet on adult tissue regulation and suggested that the transcriptional changes were unlikely to be caused by DNA methylation differences in adult liver. Methylation is compared between nine week old animals fed a common diet as adults, but derived from mothers fed different diets.
2014-03-04 | E-GEOD-52266 | biostudies-arrayexpress
Project description:Aims: Epidemiological and animal studies have shown that maternal diet can influence metabolism in adult offspring. However, the molecular mechanisms underlying these changes remain poorly understood. Here, we aim to explore phenotypes induced by maternal obesity in a mouse model and examine gene expression and epigenetic alterations in adulthood induced by maternal diet. Methods: We analyzed genetically identical male mice born from dams fed a high- or low-fat diet throughout pregnancy and until day 21 postpartum. After weaning, half of the males of each group were fed a high-fat diet, the other half a low-fat diet. We first characterized the genome-wide gene expression patterns of six tissues of adult offspring - liver, pancreas, white adipose, brain, muscle and heart [GSE40903] . We then measured DNA methylation patterns in liver at selected loci and throughout the genome. Results: Maternal diet had a significant effect on the body weight of the offspring when they are fed an obesogenic diet after weaning. Our analyses showed that maternal diet had a pervasive effect on gene expression, with a pronounced effect in liver where it affected many genes involved in inflammation, cholesterol synthesis and RXR activation. Maternal diet had no detectable effect on DNA methylation in the liver. Conclusions: Overall, our findings highlighted the persistent influence of maternal diet on adult tissue regulation and suggested that the transcriptional changes were unlikely to be caused by DNA methylation differences in adult liver. Methylation is compared between nine week old animals fed a common diet as adults, but derived from mothers fed different diets. Sequence of PCR amplification of bisulfite converted genomic DNA of numerous loci
2014-03-04 | E-GEOD-52267 | biostudies-arrayexpress
Project description:<p>Maintaining calcium levels within a narrow normal range is of critical importance for numerous different cellular functions. One of the most important regulators of blood calcium levels is parathyroid hormone (PTH), which mediates its actions through the PTH/PTHrP receptor, a Gαs-coupled receptor. Few inherited disorders are characterized by diminished blood calcium levels and elevated blood phosphate levels; some of these disorders are caused by too little PTH synthesis and/or secretion (hypoparathyroidism, HP), while others are caused by resistance towards PTH (pseudohypoparathyroidism, PHP). Only few of the inherited forms of HP (<10%) have been defined at the molecular level. In contrast, genetic mutations have been identified for several inherited forms of PHP. For example, PHP type Ia (PHP-Ia) is caused by maternally inherited mutations in those GNAS exons that encode Gαs, while autosomal dominant PHP type Ib (AD-PHP-Ib) is caused by maternal inherited deletions within or up-stream of GNAS, which are associated with abnormal GNAS methylation. However, a large number of patients with PTH-resistance and thus hypocalcemia show GNAS methylation changes, but their underlying genetic defects have not yet been defined at the DNA level. These "sporadic" patients may be affected by an autosomal recessive form of PHP-Ib (AR-PHP-Ib), which is most likely not linked to the GNAS locus. In our studies, we propose to search through exome sequence analyses for novel genetic mutations responsible for novel autosomal dominant forms of HP that are not caused by mutations in the known disease-causing genes; some of these families are large enough to perform genetic linkage studies. We furthermore propose to search for the genetic mutation(s) responsible for the autosomal recessive variant of PHP-Ib through the analysis of whole exome sequences; for these studies we focus particularly on patients, whose parents are likely to be consanguineous. The proposed efforts are expected to lead to the identification of novel genes that are involved in parathyroid development and function (HP) and genes that are involved in the establishment or maintenance of GNAS methylation (AR-PHP-Ib). </p>
| phs000476 | dbGaP
Project description:Aims: Epidemiological and animal studies have shown that maternal diet can influence metabolism in adult offspring. However, the molecular mechanisms underlying these changes remain poorly understood. Here, we aim to explore phenotypes induced by maternal obesity in a mouse model and examine gene expression and epigenetic alterations in adulthood induced by maternal diet. Methods: We analyzed genetically identical male mice born from dams fed a high- or low-fat diet throughout pregnancy and until day 21 postpartum. After weaning, half of the males of each group were fed a high-fat diet, the other half a low-fat diet. We first characterized the genome-wide gene expression patterns of six tissues of adult offspring - liver, pancreas, white adipose, brain, muscle and heart [GSE40903] . We then measured DNA methylation patterns in liver at selected loci and throughout the genome. Results: Maternal diet had a significant effect on the body weight of the offspring when they are fed an obesogenic diet after weaning. Our analyses showed that maternal diet had a pervasive effect on gene expression, with a pronounced effect in liver where it affected many genes involved in inflammation, cholesterol synthesis and RXR activation. Maternal diet had no detectable effect on DNA methylation in the liver. Conclusions: Overall, our findings highlighted the persistent influence of maternal diet on adult tissue regulation and suggested that the transcriptional changes were unlikely to be caused by DNA methylation differences in adult liver.
2014-03-04 | GSE52267 | GEO
Project description:Aims: Epidemiological and animal studies have shown that maternal diet can influence metabolism in adult offspring. However, the molecular mechanisms underlying these changes remain poorly understood. Here, we aim to explore phenotypes induced by maternal obesity in a mouse model and examine gene expression and epigenetic alterations in adulthood induced by maternal diet. Methods: We analyzed genetically identical male mice born from dams fed a high- or low-fat diet throughout pregnancy and until day 21 postpartum. After weaning, half of the males of each group were fed a high-fat diet, the other half a low-fat diet. We first characterized the genome-wide gene expression patterns of six tissues of adult offspring - liver, pancreas, white adipose, brain, muscle and heart [GSE40903] . We then measured DNA methylation patterns in liver at selected loci and throughout the genome. Results: Maternal diet had a significant effect on the body weight of the offspring when they are fed an obesogenic diet after weaning. Our analyses showed that maternal diet had a pervasive effect on gene expression, with a pronounced effect in liver where it affected many genes involved in inflammation, cholesterol synthesis and RXR activation. Maternal diet had no detectable effect on DNA methylation in the liver. Conclusions: Overall, our findings highlighted the persistent influence of maternal diet on adult tissue regulation and suggested that the transcriptional changes were unlikely to be caused by DNA methylation differences in adult liver.
2014-03-04 | GSE52266 | GEO