CGH array used to identify de novo copy number variations in offspring of BaP exposed parents.
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE128869 | GEO | 2019/04/29
REPOSITORIES: GEO
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Project description:The offspring of older fathers have an increased risk of neurodevelopmental disorders such as schizophrenia and autism. It has been proposed that de novo point mutations and copy number variants (CNVs) in the continually dividing spermatogonia underlie this association. In light of the evidence implicating CNVs with schizophrenia and autism, here we use a mouse model to test the hypothesis that the offspring of older males have an increased risk of de novo CNVs. Three-month-old and fourteen- to sixteen-month-old C57BL/6J sires were mated with three-month-old dams to create control offspring and offspring of old sires, respectively. Applying genome-wide microarray screening technology, seven distinct CNVs were identified in a discovery set of twelve offspring and their parents. Competitive quantitative PCR was employed to confirm the variants and establish their frequency in a replication set of 77 offspring and their parents. Six de novo CNVs were detected in the offspring of older sires, while none were detected in the control group. One of the de novo CNVs involved Auts2 (autism susceptibility candidate 2), and other CNVs included genes linked to schizophrenia, autism and brain development. Two of the CNVs were associated with behavioural and/or neuroanatomical phenotypic features. This is the first experimental demonstration that the offspring of older males have more de novo CNVs. The results suggest that offspring of older fathers may be at increased risk of neurodevelopmental disorders such as schizophrenia and autism via the generation of de novo CNV in the male germline. In light of the trends for delayed parenthood in many societies, and in light of the potential for these CNVs to accumulate over subsequent generations, the impact of these mechanisms on the health of future generations warrants closer scrutiny. 2 sires of advanced paternal age (12-16 months of age) and 2 control (3 months of age) sires were mated to dams (3 months of age) to create 6 offspring of advanced paternal age (APA) and 6 control offspring (C), respectively, with an even number of sexes within each group of offspring. A commerical aCGH and a custom CNV array (both supplied by Agilent) were used in combination to detect copy number variations in the genomes of the offspring and their parents. DNA from all male animals was hybridized against a male reference animal and that from all female animals against a female reference animal.
2011-07-12 | E-GEOD-29454 | biostudies-arrayexpress
Project description:The offspring of older fathers have an increased risk of neurodevelopmental disorders such as schizophrenia and autism. It has been proposed that de novo point mutations and copy number variants (CNVs) in the continually dividing spermatogonia underlie this association. In light of the evidence implicating CNVs with schizophrenia and autism, here we use a mouse model to test the hypothesis that the offspring of older males have an increased risk of de novo CNVs. Three-month-old and fourteen- to sixteen-month-old C57BL/6J sires were mated with three-month-old dams to create control offspring and offspring of old sires, respectively. Applying genome-wide microarray screening technology, seven distinct CNVs were identified in a discovery set of twelve offspring and their parents. Competitive quantitative PCR was employed to confirm the variants and establish their frequency in a replication set of 77 offspring and their parents. Six de novo CNVs were detected in the offspring of older sires, while none were detected in the control group. One of the de novo CNVs involved Auts2 (autism susceptibility candidate 2), and other CNVs included genes linked to schizophrenia, autism and brain development. Two of the CNVs were associated with behavioural and/or neuroanatomical phenotypic features. This is the first experimental demonstration that the offspring of older males have more de novo CNVs. The results suggest that offspring of older fathers may be at increased risk of neurodevelopmental disorders such as schizophrenia and autism via the generation of de novo CNV in the male germline. In light of the trends for delayed parenthood in many societies, and in light of the potential for these CNVs to accumulate over subsequent generations, the impact of these mechanisms on the health of future generations warrants closer scrutiny. 2 sires of advanced paternal age (12-16 months of age) and 2 control (3 months of age) sires were mated to dams (3 months of age) to create 6 offspring of advanced paternal age (APA) and 6 control offspring (C), respectively, with an even number of sexes within each group of offspring. A commerical aCGH and a custom CNV array (both supplied by Agilent) were used in combination to detect copy number variations in the genomes of the offspring and their parents. DNA from all male animals was hybridized against a male reference animal and that from all female animals against a female reference animal.
2011-07-12 | E-GEOD-29455 | biostudies-arrayexpress
Project description:The offspring of older fathers have an increased risk of neurodevelopmental disorders such as schizophrenia and autism. It has been proposed that de novo point mutations and copy number variants (CNVs) in the continually dividing spermatogonia underlie this association. In light of the evidence implicating CNVs with schizophrenia and autism, here we use a mouse model to test the hypothesis that the offspring of older males have an increased risk of de novo CNVs. Three-month-old and fourteen- to sixteen-month-old C57BL/6J sires were mated with three-month-old dams to create control offspring and offspring of old sires, respectively. Applying genome-wide microarray screening technology, seven distinct CNVs were identified in a discovery set of twelve offspring and their parents. Competitive quantitative PCR was employed to confirm the variants and establish their frequency in a replication set of 77 offspring and their parents. Six de novo CNVs were detected in the offspring of older sires, while none were detected in the control group. One of the de novo CNVs involved Auts2 (autism susceptibility candidate 2), and other CNVs included genes linked to schizophrenia, autism and brain development. Two of the CNVs were associated with behavioural and/or neuroanatomical phenotypic features. This is the first experimental demonstration that the offspring of older males have more de novo CNVs. The results suggest that offspring of older fathers may be at increased risk of neurodevelopmental disorders such as schizophrenia and autism via the generation of de novo CNV in the male germline. In light of the trends for delayed parenthood in many societies, and in light of the potential for these CNVs to accumulate over subsequent generations, the impact of these mechanisms on the health of future generations warrants closer scrutiny.
2011-07-12 | GSE29455 | GEO
Project description:The offspring of older fathers have an increased risk of neurodevelopmental disorders such as schizophrenia and autism. It has been proposed that de novo point mutations and copy number variants (CNVs) in the continually dividing spermatogonia underlie this association. In light of the evidence implicating CNVs with schizophrenia and autism, here we use a mouse model to test the hypothesis that the offspring of older males have an increased risk of de novo CNVs. Three-month-old and fourteen- to sixteen-month-old C57BL/6J sires were mated with three-month-old dams to create control offspring and offspring of old sires, respectively. Applying genome-wide microarray screening technology, seven distinct CNVs were identified in a discovery set of twelve offspring and their parents. Competitive quantitative PCR was employed to confirm the variants and establish their frequency in a replication set of 77 offspring and their parents. Six de novo CNVs were detected in the offspring of older sires, while none were detected in the control group. One of the de novo CNVs involved Auts2 (autism susceptibility candidate 2), and other CNVs included genes linked to schizophrenia, autism and brain development. Two of the CNVs were associated with behavioural and/or neuroanatomical phenotypic features. This is the first experimental demonstration that the offspring of older males have more de novo CNVs. The results suggest that offspring of older fathers may be at increased risk of neurodevelopmental disorders such as schizophrenia and autism via the generation of de novo CNV in the male germline. In light of the trends for delayed parenthood in many societies, and in light of the potential for these CNVs to accumulate over subsequent generations, the impact of these mechanisms on the health of future generations warrants closer scrutiny.
2011-07-12 | GSE29454 | GEO
Project description:To characterise the transcriptome of mouse placental junctional zone cells in Control litters (deletion of the maternally-inherited and silent Igf2 allele, with normal Igf2 levels in whole litters) in UE litters (dams carried offspring with a deletion of the paternally-inherited Igf2 allele in the placental endocrine cells with diminished Igf2 production from the endocrine cells in whole litters), we performed single nucleus RNA sequencing on the placenta Junctional zone 8 Control placentas (offspring sex: 4M:4F) and 8 UE placentas (offspring sex: 4M:4F) in 2 batches each.
2023-04-30 | GSE229514 | GEO
Project description:Here, we describe the use of high-throughput sequencing to examine the developmental basis of placental growth defects observed in the male offspring of alcohol-exposed fathers. We exposed C57BL/6J male mice to 10% ethanol for ten weeks, then bred them to naïve CD-1 dams. The male offspring of ethanol-exposed sires exhibited placental growth defects. We isolated total RNA from four F1 male placentae from each control and ethanol preconception treatment and conducted deep-sequencing analysis of the transcriptome. These studies identified programmed increases in the genetic pathways controlling oxidative phosphorylation, mitochondrial function, and Sirtuin signaling. This study furthers our understanding of growth and metabolic phenotypes induced by preconception paternal exposures.
2021-07-15 | GSE179973 | GEO
Project description:Maternal diet is associated with the development of metabolism-related and other non-communicable diseases in offspring. Underlying mechanisms, functional profiles, and molecular markers are only starting to be revealed. Here, we explored the physiological and molecular impact of maternal Western-style diet on the liver of male and female offspring. C57BL/6 dams were exposed to either a low fat/low cholesterol diet (LFD) or a Western-style high fat/high cholesterol diet (WSD) for six weeks before mating, as well as during gestation and lactation. Dams and offspring were sacrificed at postnatal day 14, and body, liver, and blood parameters were assessed. The impact of maternal WSD on the pups' liver gene expression was characterised by whole-transcriptome microarray analysis. Exclusively male offspring had significantly higher body weight upon maternal WSD. In offspring of both sexes of WSD dams, liver and blood parameters, as well as hepatic gene expression profiles were changed. In total, 686 and 604 genes were differentially expressed in liver (pM-bM-^IM-$0.01) of males and females, respectively. Only 10% of these significantly changed genes overlapped in both sexes. In males, in particular alterations of gene expression with respect to developmental functions and processes were observed, such as Wnt/beta-catenin signalling. In females, mainly genes important for lipid metabolism, including cholesterol synthesis, were changed. We conclude that maternal WSD affects physiological parameters and induces substantial changes in the molecular profile of the liver in two-week-old pups. Remarkably, the observed biological responses of the offspring reveal pronounced sex-specificity. C57BL/6 dams were exposed to either a low fat/low cholesterol diet (LFD) or a Western-style high fat/high cholesterol diet (WSD) as six weeks pre-treatment before mating, as well as during gestation and lactation. Offspring were sacrificed at postnatal week two, livers were removed and RNA samples were subjected to gene expression profiling.
2013-11-27 | E-GEOD-46359 | biostudies-arrayexpress
Project description:Gene copy number variations (CNVs) involved in phenotypic variations have already been shown in plants, but genome-wide testing of CNVs for adaptive variation was not doable until recent technological developments. Thus, reports of the genomic architecture of adaptation involving CNVs remain scarce to date. Here, we investigated F1 progenies of an intra-provenance cross (north-north cross, 58th parallel) and an inter-provenances cross (north-south cross, 58th/49th parallels) for CNVs using comparative genomic hybridization on arrays of probes targeting gene sequences in balsam poplar (Populus balsamifera L.), a wide-spread North American forest tree. Results: A total of 1,721 genes were found in varying copy numbers over the set of 19,823 tested genes. These gene CNVs presented an estimated average size of 8.3 kb and were distributed over poplar’s 19 chromosomes including 22 hotspot regions. Gene CNVs number was higher for the inter-provenance progeny in accordance with an expected higher genetic diversity related to the composite origin of this family. Regression analyses between gene CNVs and seven adaptive trait variations resulted in 23 significant links; among these adaptive gene CNVs, 30% were located in hotspots. One-to-five gene CNVs were found related to each of the measured adaptive traits and annotated for both biotic and abiotic stress responses. These annotations can be related to the occurrence of a higher pathogenic pressure in the southern parts of balsam poplar’s distribution, and higher photosynthetic assimilation rates and water-use efficiency at high-latitudes. Overall, our findings suggest that gene CNVs typically having higher mutation rates than SNPs, may in fact represent efficient adaptive variations against fast-evolving pathogens.
2018-09-11 | GSE119764 | GEO
Project description:Maternal obesity can program metabolic syndrome in offspring but the mechanisms are not well characterized. Moreover, the consequences of maternal overnutrition in the absence of frank obesity remain poorly understood. This study aimed to determine the effects of maternal consumption of a high fat-sucrose diet on the skeletal muscle metabolic and transcriptional profiles of adult offspring. Female Sprague Dawley rats were fed either a diet rich in saturated fat and sucrose (HFD, 23.5% fat, 20% sucrose wt/wt) or a standard chow diet (NFD, 7% fat, 10% sucrose w/w) for the 3 weeks prior to mating and throughout pregnancy and lactation. Although maternal weights were not different between groups at conception or weaning, HFD dams were ~22% heavier than chow fed dams from mid-pregnancy until 4 days post-partum. Adult male offspring of HFD dams were not heavier than controls but demonstrated features of insulin resistance including elevated plasma insulin concentration (+40%, P<0.05). Next Generation mRNA Sequencing was used to identify differentially expressed genes in the soleus muscle of offspring, and Gene Set Enrichment Analysis (GSEA) to detect coordinated changes that are characteristic of a biological function. GSEA identified 15 pathways enriched for up-regulated genes, including cytokine signaling (P<0.005), starch and sucrose metabolism (P<0.017), and inflammatory response (P<0.024). A further 8 pathways were significantly enriched for down-regulated genes including oxidative phosphorylation (P<0.004) and electron transport (P<0.022). Western blots confirmed a ~60% reduction in the phosphorylation of the insulin signaling protein Akt (P<0.05) and ~70% reduction in mitochondrial complexes II (P<0.05) and V expression (P<0.05). On a normal diet, offspring of HFD dams developed an insulin resistant phenotype, with transcriptional evidence of muscle cytokine activation, inflammation and mitochondrial dysfunction. These data indicate that maternal overnutrition, even in the absence of pre-pregnancy obesity can promote metabolic dysregulation and predispose offspring to type 2 diabetes. Messenger RNA profile of skeletal muscle of male offspring from female Sprague Dawley rats fed either a diet rich in saturated fat and sucrose (HFD, 23.5% fat, 20% sucrose wt/wt) or a standard chow diet (NFD, 7% fat, 10% sucrose w/w) for the 3 weeks prior to mating and throughout pregnancy and lactation. There were 5 HFD samples compared to 6 NFD control samples.
2013-08-13 | E-GEOD-49797 | biostudies-arrayexpress
Project description:Background: Following cardiac injury, whether the heart is permanently damaged or regenerating, distal organs are subjected to changes in physiological function. It remains largely unknown whether a cardiac lesion can affect gametes and transmit heritable changes to subsequent generations. Here, we report the influence of paternal cardiac injury on the following generation. Methods: We studied the intergenerational influence of neonatal cardiac injury in the mouse. Neonatal male mice were subjected to ventricular cryoinjury, crossed at adulthood, and their sires were compared with litters derived from uninjured male mice. We used echocardiography, histology, and single nuclei RNA-sequencing to thoroughly characterize cardiac morphology, composition, function, and response to cardiac insult. Results: We show that paternal cardiac injury affects the heart morphology of offspring under physiological conditions. Furthermore, in response to the same injury, the F1 generation derived from injured fathers shows better systemic and cardiac recovery, with non-pathological left ventricular enlargement and improved cardiac function. This is accompanied by the activation of the immune system healing program at 3 weeks post-injury, together with enhanced transcription of genes associated with physiological hypertrophy. Conclusions: The memory of a paternal neonatal lesion can be transmitted to offspring and improve their recovery from a cardiac insult.
2024-11-08 | GSE254827 | GEO