Effect of Advanced Paternal Age on Copy Number Variation in Offspring
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE29456 | GEO | 2011/07/12
SECONDARY ACCESSION(S): PRJNA141573
REPOSITORIES: GEO
Similar Datasets
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: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 | GSE29454 | 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 | GSE29455 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2015-01-16 | E-GEOD-65048 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below.
2015-01-16 | GSE65048 | GEO
Project description:Many risk factors of cancer have been established, but the contribution of paternal age in this regard remains largely unexplored. To further understand the etiology of cancer, we investigated the relationship between paternal age and cancer incidence using PLCO cohort. Cox proportional hazards models were performed to assess the association between paternal age and the risk of cancers. During follow-up time (median 11.5 years), 18,753 primary cancers occurred. Paternal age was associated with reduced risk of cancers of the female genitalia (HR, 0.79; 95%CI, 0.66-0.94; P = 0.008) as well as cancers of the respiratory and intrathoracic organs (HR, 0.78; 95%CI, 0.63-0.97; P = 0.026). The association was stronger for lung cancer (HR, 0.67; 95%CI, 0.52-0.86; P = 0.002). The subgroup analysis suggested that age, gender, smoking and BMI were related to the decreased cancer incidence of the respiratory and intrathoracic organs, lung and the female genitalia. Positive linear associations were observed between paternal age and cancer incidence of the female genitalia, respiratory and intrathoracic organs and the lungs. These findings indicate that advanced paternal age is an independent protective factor against various cancers in offspring.
| S-EPMC7906132 | biostudies-literature
Project description:The prevalence of some autoimmune diseases is greater in females compared with males, although disease severity is often greater in males. The reason for this sexual dimorphism is unknown, but it may reflect negative selection of Y chromosome-bearing sperm during spermatogenesis or male fetuses early in the course of conception/pregnancy. Previously, we showed that the sexual dimorphism in experimental autoimmune encephalomyelitis (EAE) is associated with copy number variation (CNV) in Y chromosome multicopy genes. Here, we test the hypothesis that CNV in Y chromosome multicopy genes influences the paternal parent-of-origin effect on EAE susceptibility in female mice.We show that C57BL/6 J consomic strains of mice possessing an identical X chromosome and CNV in Y chromosome multicopy genes exhibit sperm head abnormalities and female-biased sex ratio. This is consistent with X-Y intragenomic conflict arising from an imbalance in CNV between homologous X:Y chromosome multicopy genes. These males also display paternal transmission of EAE to female offspring and differential loading of microRNAs within the sperm nucleus. Furthermore, in humans, families of probands with multiple sclerosis similarly exhibit a female-biased sex ratio, whereas families of probands affected with non-sexually dimorphic autoimmune diseases exhibit unbiased sex ratios.These findings provide evidence for a mechanism at the level of the male gamete that contributes to the sexual dimorphism in EAE and paternal parent-of-origin effects in female mice, raising the possibility that a similar mechanism may contribute to the sexual dimorphism in multiple sclerosis.
| S-EPMC4396973 | biostudies-literature
Project description:Male age may directly or indirectly affect the fitness of their female mating partners and their joint progeny. While in some taxa of insects, old males make better mates and fathers, young males excel in others. Males of most social Hymenoptera are relatively short lived and because of testis degeneration have only a limited sperm supply. In contrast, the wingless fighter males of the ant Cardiocondyla obscurior live for several weeks and produce sperm throughout their lives. Wingless males engage in lethal combat with rival males and the winner of such fights can monopolize mating with all female sexuals that emerge in their nests over a prolonged timespan. Here, we investigate if male age has an influence on sperm quality, the queen's lifespan and productivity, and the size and weight of their offspring. Queens mated to one-week or six-week-old males did not differ in life expectancy and offspring production, but the daughters of young males were slightly heavier than those of old males. Our data suggest negligible reproductive senescence of C. obscurior males even at an age, which only few of them reach. This matches the reproductive strategy of Cardiocondyla ants, in which freshly emerging female sexuals rarely have the option to mate with males other than the one present in their natal nest.
| S-EPMC6303694 | biostudies-literature