Technical advances contribute to the study of genomic imprinting.
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ABSTRACT:
SUBMITTER: Li Y
PROVIDER: S-EPMC6586256 | biostudies-literature | 2019 Jun
REPOSITORIES: biostudies-literature
Publications
Technical advances contribute to the study of genomic imprinting.
PLoS genetics 20190620 6
Genomic imprinting in mammals was discovered over 30 years ago through elegant embryological and genetic experiments in mice. Imprinted genes show a monoallelic and parent of origin-specific expression pattern; the development of techniques that can distinguish between expression from maternal and paternal chromosomes in mice, combined with high-throughput strategies, has allowed for identification of many more imprinted genes, most of which are conserved in humans. Undoubtedly, technical progre ...[more]
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Project description:Genomic imprinting refers to an epigenetic marking of genes that results in monoallelic expression. This parent-of-origin dependent phenomenon is a notable exception to the laws of Mendelian genetics. Imprinted genes are intricately involved in fetal and behavioral development. Consequently, abnormal expression of these genes results in numerous human genetic disorders including carcinogenesis. This paper reviews genomic imprinting and its role in human disease. Additional information about imprinted genes can be found on the Genomic Imprinting Website at http://www.geneimprint.com.
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Project description:Genomic imprinting shapes the genotype-phenotype relationship by creating an asymmetry between the influences of paternally and maternally inherited gene copies. Consequently, imprinting can impact heritable and nonheritable variation, resemblance of relatives, and evolutionary dynamics. Although previous analyses have identified some of the quantitative genetic consequences of imprinting, we lack a framework that cleanly separates the influence of imprinting from other components of variation, particularly dominance. Here we apply a simple orthogonal genetic model to evaluate the roles of genetic (additive and dominance) and epigenetic (imprinting) effects. Imprinting increases the resemblance of relatives who share the expressed allele, and therefore increases variance among families of full or half-siblings. However, only part of this increased variance is heritable and contributes to selection responses. When selection is within, or among, families sharing only a single parent (half-siblings), which is common in selective breeding programs, imprinting can alter overall responses. Selection is more efficient when it acts among families sharing the expressed parent, or within families sharing the parent with lower expression. Imprinting also affects responses to sex-specific selection. When selection is on the sex whose gene copy has lower expression, the response is diminished or delayed the next generation, although the long-term response is unaffected. Our findings have significant implications for understanding patterns of variation, interpretation of short-term selection responses, and the efficacy of selective breeding programs, demonstrating the importance of considering the independent influence of genomic imprinting in quantitative genetics.
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Project description:Purpose of reviewGenomic imprinting refers to preferential allele-specific gene expression. DNA methylation-based molecular mechanisms regulate establishment and maintenance of parental imprints during early embryo development and gametogenesis. Because of the coincident timing, a potential association between assisted reproductive technology (ART) procedures and imprinting defects has been investigated in various studies. In this review, we provide an overview of genomic imprinting and present a summary of the relevant clinical data.Recent findingsART procedures affect DNA methylation pattern, parental imprinting status, and imprinted gene expression in the mouse embryo. In humans, several case series suggested an association between ART and imprinting disorders, with a three-fold to six-fold higher prevalence of ART use among children born with Beckwith-Wiedemann syndrome compared to the general population. However, more recent studies failed to support these findings and could not demonstrate an association between imprinting disorders and ARTs, independent of subfertility.SummaryART procedures may affect methylation status of imprinted regions in the DNA, leading to imprinting disorders. Although the low prevalence of imprinting disorders makes it challenging to perform conclusive clinical trials, further studies in large registries are required to determine the real impact of ARTs on their occurrence.
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