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Genetic Syndromes and Imprinting
Research Guide
What is Genetic Syndromes and Imprinting?
Genetic syndromes and imprinting refers to the phenomenon of genomic imprinting where certain genes are expressed in a parent-of-origin-specific manner, leading to epigenetic regulation through DNA methylation and contributing to syndromes such as Prader-Willi and Angelman.
Genomic imprinting involves parental influence on gene expression regulated by epigenetic mechanisms like DNA methylation at imprint control regions. Imprinted genes play roles in syndromes including Prader-Willi syndrome and Angelman syndrome, with non-coding RNA involved in their networks. The field encompasses 40,756 works with growth data unavailable over the past five years.
Topic Hierarchy
Why It Matters
Genomic imprinting underlies syndromes like Prader-Willi and Angelman, which arise from parent-of-origin-specific gene expression failures. Okano et al. (1999) showed that DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation critical to imprinting and mammalian development, impacting fertility and viability in knockout models. Herman et al. (1996) developed methylation-specific PCR to map CpG island methylation patterns, enabling precise analysis of imprinted gene regulation, X chromosome inactivation, and tumor suppressor silencing in cancer. Fraga et al. (2005) demonstrated epigenetic differences accumulating over the lifetime of monozygotic twins, explaining phenotypic discordance despite identical genotypes, with implications for disease susceptibility studies.
Reading Guide
Where to Start
"DNA Methyltransferases Dnmt3a and Dnmt3b Are Essential for De Novo Methylation and Mammalian Development" by Okano et al. (1999), as it provides foundational evidence on DNA methylation's role in imprinting and development, directly relevant to syndromes like Prader-Willi.
Key Papers Explained
Okano et al. (1999) "DNA Methyltransferases Dnmt3a and Dnmt3b Are Essential for De Novo Methylation and Mammalian Development" establishes the enzymes required for methylation marks in imprinting. Herman et al. (1996) "Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands" builds on this by offering a detection method for those marks in imprinted genes. Fraga et al. (2005) "Epigenetic differences arise during the lifetime of monozygotic twins" extends the framework to dynamic changes, showing how methylation drifts affect imprinting-related phenotypes.
Paper Timeline
Most-cited paper highlighted in red. Papers ordered chronologically.
Advanced Directions
Research focuses on epigenetic regulation of imprinted genes and DNA methylation mechanisms, as reflected in the 40,756 works. Core papers like those by Okano et al. (1999) and Herman et al. (1996) remain central, with no recent preprints or news indicating ongoing refinements in methods for syndromes such as Prader-Willi and Angelman.
Papers at a Glance
| # | Paper | Year | Venue | Citations | Open Access |
|---|---|---|---|---|---|
| 1 | Second-generation PLINK: rising to the challenge of larger and... | 2015 | GigaScience | 13.0K | ✓ |
| 2 | Principal components analysis corrects for stratification in g... | 2006 | Nature Genetics | 10.5K | ✕ |
| 3 | DNA Methyltransferases Dnmt3a and Dnmt3b Are Essential for De ... | 1999 | Cell | 6.0K | ✓ |
| 4 | Methylation-specific PCR: a novel PCR assay for methylation st... | 1996 | Proceedings of the Nat... | 5.6K | ✓ |
| 5 | Genome-wide maps of chromatin state in pluripotent and lineage... | 2007 | Nature | 4.1K | ✓ |
| 6 | Histone Demethylation Mediated by the Nuclear Amine Oxidase Ho... | 2004 | Cell | 3.9K | ✓ |
| 7 | Mutation of the mouse klotho gene leads to a syndrome resembli... | 1997 | Nature | 3.8K | ✕ |
| 8 | Epigenetic differences arise during the lifetime of monozygoti... | 2005 | Proceedings of the Nat... | 3.6K | ✓ |
| 9 | A gene atlas of the mouse and human protein-encoding transcrip... | 2004 | Proceedings of the Nat... | 3.5K | ✓ |
| 10 | Tet Proteins Can Convert 5-Methylcytosine to 5-Formylcytosine ... | 2011 | Science | 3.3K | ✕ |
Frequently Asked Questions
What is genomic imprinting?
Genomic imprinting is the parent-of-origin-specific expression of certain genes regulated by epigenetic marks like DNA methylation. It controls imprinted gene networks through imprint control regions and non-coding RNA. Disruptions lead to syndromes such as Prader-Willi and Angelman.
How does DNA methylation regulate imprinting?
DNA methylation at CpG islands silences one parental allele in imprinted genes. Okano et al. (1999) established that Dnmt3a and Dnmt3b perform de novo methylation essential for this process and mammalian development. Herman et al. (1996) introduced methylation-specific PCR to detect these patterns accurately.
What are key syndromes linked to imprinting?
Prader-Willi syndrome and Angelman syndrome result from deletions or imprinting defects on chromosome 15, depending on parental origin. Loss of paternal or maternal imprinted gene expression causes distinct phenotypes. These illustrate parental influence on gene expression.
What methods detect methylation in imprinted genes?
Methylation-specific PCR assays the methylation status of CpG islands, as described by Herman et al. (1996). This technique supports studies of imprinted gene regulation and epigenetic silencing. It has applications in analyzing tumor suppressor genes and X inactivation.
How do epigenetic changes affect monozygotic twins?
Epigenetic differences, including DNA methylation variations, arise during the lifetime of monozygotic twins despite shared genotypes, per Fraga et al. (2005). These changes contribute to phenotypic discordance in disease susceptibility and anthropomorphic traits. They highlight environmental influences on epigenomes.
What is the role of non-coding RNA in imprinting?
Non-coding RNA participates in regulating imprinted gene networks alongside DNA methylation. Imprint control regions coordinate these mechanisms for parent-specific expression. This regulation is central to syndromes like Prader-Willi and Angelman.
Open Research Questions
- ? How do lifetime epigenetic drifts in monozygotic twins influence imprinting stability and disease discordance?
- ? What precise mechanisms link Dnmt3a/Dnmt3b deficiencies to imprinting failures in developmental syndromes?
- ? How do non-coding RNAs interact with imprint control regions to maintain parent-of-origin-specific expression?
- ? What distinguishes methylation patterns in imprinted genes versus tumor suppressor silencing?
- ? How do chromatin states in pluripotent cells regulate the establishment of imprinting marks?
Recent Trends
The field maintains 40,756 works with five-year growth data unavailable, centering on established papers like Okano et al. with 5987 citations on Dnmt3a/Dnmt3b roles and Herman et al. (1996) with 5642 citations on methylation-specific PCR. No recent preprints or news coverage in the last 12 months signals steady reliance on methylation and epigenetic mechanisms for imprinting in syndromes.
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