Mus musculus
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ABSTRACT:
PROVIDER: PRJNA153983 | ENA |
REPOSITORIES: ENA
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Project description:This SuperSeries is composed of the following subset Series: GSE29454: Effect of Advanced Paternal Age on Copy Number Variation in Offspring (custom array) GSE29455: Effect of Advanced Paternal Age on Copy Number Variation in Offspring (commercial array) Refer to individual Series
2011-07-12 | E-GEOD-29456 | biostudies-arrayexpress
Project description:Effect of Advanced Paternal Age on Copy Number Variation in Offspring (commercial array)
| PRJNA153985 | ENA
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:Background: Epidemiological studies have reported an association between advanced paternal age at conception and an increased risk of neurodevelopmental disorders in offspring, such as autism spectrum disorder. Evidence suggests that DNA methylation alterations in sperm of older men may be transmitted to the feto-placental unit and associated with offspring brain development and behavioral differences later in childhood. Objective: We aimed to assess the association of advanced paternal age with DNA methylation alterations in the human placenta and compare the results to previous findings in sperm. Methods: For this study, 64 placenta samples from the 3D (Design, Develop, Discover) prospective birth cohort study were categorized based on paternal age at conception. DNA methylation of the placenta was interrogated using the Illumina 850K array. There were no differentially methylated sites found to be statistically significant after correction for multiple comparisons, therefore sites with significant nominal p-values <0.05 were assessed and used to define differentially methylated regions (DMRs) associated with genes. Results: Advanced paternal age was associated with DNA methylation alterations in the placenta at up to 688 genes, with a predominance of hypomethylation (65%), including at 8 imprinted loci. About 7% of genes with age-associated DNA methylation changes in placenta overlapped with genes previously reported to show altered DNA methylation in sperm of older men; seven genes common to placenta and sperm had previously been identified in association with susceptibility to autism spectrum disorder. Amongst loci most affected, we found evidence of sex-specific hypermethylation at genes linked to neurodevelopment (GRM7, EBF3, FOXG1). Conclusion: Our findings suggest that advanced paternal age at conception is associated with altered DNA methylation in the human placenta, including at genes tied to neurodevelopment. This study highlights the use of the placenta DNA methylome as a surrogate marker for the potential impact of advanced paternal age on the child.
2025-12-11 | GSE273723 | GEO
Project description:Investigation of genome-wide germline copy number mutations in mice after parental exposure to 3 Gy of acute X-rays The level of copy number mutations in offspring of exposed paternal mice was substantially increased when compared to the control Overall 262 samples were used of which 93 were control samples and 169 treated samples. The control samples came from offspring of parents (C57BL6/J (male) and CBA/Ca (female)) with sham -ir while the treated samples were from offspring of 3 Gy whole-body acute irradiated paternal and non-exposed maternal. The treated samples classified into two groups: post-meiotic and pre-meiotic according to exposed status of the sperm that gave rise to the offspring. The reference sample for each offspring was equal mixture of paternal and maternal DNA.
2015-02-04 | E-GEOD-65521 | biostudies-arrayexpress
Project description:The diet consumed by fathers prior to procreation impacts metabolic phenotypes in their offspring, but the mechanisms underlying such intergenerational information transfer remain obscure. Here, we carried out extensive analysis of cytosine methylation patterns in murine sperm, generating whole genome methylation maps for 4 pools of sperm samples and for 12 individual sperm samples, as well as 61 genome-scale reduced-representation bisulfite sequencing (RRBS) methylation maps, using samples obtained from male mice consuming various diets. We found that epivariation, either stochastic or due to unknown demographic or environmental factors, was a far stronger contributor to the sperm methylome than was the diet consumed. Variation in cytosine methylation was particularly dramatic over tandem repeat families, including ribosomal DNA (rDNA) repeats, and rDNA methylation levels were heritable from one generation to the next. However, rDNA methylation was strongly correlated with genetic variation in rDNA copy number, and analysis of hundreds of sperm samples revealed no consistent effect of diet on rDNA copy number or methylation level in sperm, indicating that paternal diet exerts an rDNA methylation-independent effect on offspring gene expression. These results reveal loci of genetic and epigenetic lability in the mammalian genome, but strongly argue against a direct mechanistic role for sperm cytosine methylation in dietary reprogramming of offspring metabolism.
2015-12-17 | GSE75323 | GEO
Project description:Investigation of genome-wide germline copy number mutations in mice after parental exposure to 3 Gy of acute X-rays The level of copy number mutations in offspring of exposed paternal mice was substantially increased when compared to the control
2015-02-04 | GSE65521 | GEO