Publications by authors named "Bernhard Horsthemke"
Article Synopsis
- - Epigenetic control systems involve modifications to chromatin, such as DNA methylation and histone changes, which regulate gene expression and are crucial for processes like cell fate and genomic imprinting.
- - Abnormal chromatin states, known as epimutations, can arise without genetic changes (primary) or due to mutations in regulatory elements (secondary). These epimutations can contribute to diseases like imprinting disorders and fragile X syndrome.
- - DNA methylation testing has become a key diagnostic tool for several diseases, helping to identify epigenetic changes that lead to altered gene expression.
Article Synopsis
- Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer that often resists conventional therapies, with over 90% of cases linked to a KRAS mutation, making treatment extremely challenging.
- Researchers studied primary tumor cells from genetically modified mice to understand how PDAC cells develop resistance to MEK inhibitors, analyzing various molecular data to track changes over time.
- They discovered that resistance evolved through the expansion of a single cell clone with significant DNA methylation changes, which were reversible upon drug withdrawal and could be targeted with DNA methyltransferase inhibitors.
Article Synopsis
- Increasing evidence suggests that epigenetic changes, particularly DNA methylation of the POMC gene, can increase the risk of obesity, with a notable 1.4-fold risk linked to specific hypermethylation patterns.
- A human embryonic stem cell model was used to study how these methylation states are established early in development, showing that reduced DNA methylation is associated with the formation of hypothalamic neurons that express the POMC gene.
- Treatment with an MC4R agonist in individuals with hypermethylation resulted in an average body weight reduction of about 4.66% over several months, highlighting a potential therapeutic approach for addressing this epigenetic obesity risk variant.
Article Synopsis
- The inheritance of acquired traits in mammals is a debated issue in biology, particularly regarding the transmission of DNA methylation patterns across generations.
- Recent research by Takahashi et al. shows that inserting CpG-free DNA into a CpG island can lead to lasting changes in DNA methylation that are passed down even after the foreign DNA is removed.
- The authors of the synopsis raise questions about the interpretation of these findings and explore other possible explanations for the observed transgenerational effects.
Article Synopsis
- - The study focuses on identifying disease-associated genes on chromosome X, which is difficult due to its unique inheritance patterns.
- - Researchers found a notable prevalence of genes related to cognitive functions and seizures on chromosome X and identified 127 genes that may be associated with known disorders.
- - Utilizing machine learning, the team classified 247 genes as likely disease-associated and highlighted specific damaging variants in CDK16 and TRPC5 linked to intellectual disabilities and autism spectrum disorders.
Article Synopsis
- DNA methylation can be influenced by the environment, leading researchers to explore if psychological therapies can affect these epigenetic processes.
- A study aimed to replicate changes in DNA methylation related to therapy in monocytes from 60 women with PTSD and to discover new genomic regions affected by therapy using whole-genome sequencing in two patients.
- Findings showed no significant therapy-related DNA methylation changes in commonly studied genes, and any detected changes in other genomic regions weren’t consistent across the entire patient group, suggesting limited impact of therapy on DNA methylation in PTSD patients.
Article Synopsis
- Modern epigenetics has evolved over the past 40 years, but it faces issues like misconceptions and poor research methods.
- A major misconception is that chromatin modifications directly respond to the environment and can be inherited, whereas in reality, gene expression is primarily influenced by signaling pathways and transcription factors.
- To address these misconceptions and improve research accuracy, it’s essential to use precise definitions, understand methodological issues, and focus on foundational concepts in molecular and cellular biology.
Article Synopsis
- Circular RNAs (circRNAs) play a role in regulating processes like adipogenesis and can be influenced by single nucleotide polymorphisms (SNPs) associated with BMI.
- The study found that BMI-related SNPs are more commonly located in circRNA genomic regions, especially in females compared to males.
- Further analysis showed that circRNAs are also associated with SNPs in several other health-related traits, indicating that genetic variations may influence BMI via circRNAs.
Article Synopsis
- Noncoding repeat expansions are genetic mutations linked to disorders in the central nervous system but are often overlooked by standard diagnostic methods! * Specific techniques like repeat-primed PCR and bioinformatics tools, such as ExpansionHunter, are needed to identify these pathogenic expansions! * GC-rich repeat expansions, affecting gene regulatory regions, can cause diseases through RNA toxicity or loss of gene function, depending on their characteristics!
Article Synopsis
- Research indicates that male infertility may be linked to abnormal sperm DNA methylation patterns, particularly in specific genes, but previous studies showed no clear connection in severely oligozoospermic men due to confounding factors.
- A comparison of testicular germ cell (TGC) methylomes between men with cryptozoospermia (CZ) and controls revealed 271 differentially methylated regions (DMRs), with a majority hypermethylated in CZ samples and associated with genes important for spermatogenesis.
- The study concluded that abnormal sperm development correlates with changes in DNA methylation in testicular germ cells, affecting gene expression and spermatogenesis.
Article Synopsis
- Prader-Willi syndrome (PWS) is a rare genetic disorder marked by low muscle tone, intellectual disabilities, and issues with hormone production that lead to overeating and obesity, often linked to gene loss on chromosome 15.
- A 46-year-old patient with Prader-Willi-like syndrome (PWLS) exhibited similar symptoms despite normal PWS genetic tests, revealing a specific genetic variant potentially linked to her condition.
- The case emphasizes the complexity of diagnosing genetic disorders and the ongoing research needed to understand the connections between genetic variants and clinical symptoms.
Article Synopsis
- Lasp1 is a protein linked to breast cancer and tumor invasion, but its regulatory role in aggressive cell transformation is not fully understood.
- This study reveals that Lasp1 is connected to chronic inflammatory arthritis and plays a crucial role in cell-to-cell interactions involving Cadherin-11 and β-Catenin in synoviocytes from patients and mouse models.
- Blocking or removing Lasp1 impacts tissue formation and inflammation, indicating it may be a potential therapeutic target for treating severe inflammatory joint conditions.
Background: MAGEL2-associated Schaaf-Yang syndrome (SHFYNG, OMIM #615547, ORPHA: 398069), which was identified in 2013, is a rare disorder caused by truncating variants of the paternal copy of MAGEL2, which is localized in the imprinted region on 15q11.2q13. The phenotype of SHFYNG in childhood partially overlaps with that of the well-established Prader-Willi syndrome (PWS, OMIM #176270).
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- Male fertility is impacted by paternal age, leading to increased germ cell mutations and potential congenital diseases in offspring.
- A study of 198 healthy men revealed that while semen and hormone profiles remain stable over time, sperm DNA stability declines after age 60, with significant methylation changes near genes related to neuronal development.
- The findings suggest a unique pattern of ageing in male germ cells, which may contribute to reduced fertility and health issues for children of older fathers.
Article Synopsis
- Numerous studies have indicated abnormal DNA methylation of imprinted genes like MEST and H19 in the sperm of men with oligozoospermia, but the extent and prevalence of these methylation changes were previously unclear.
- In a study involving 133 men, researchers categorized samples into normal controls and two types of abnormally methylated oligozoospermic groups, discovering widespread abnormal methylation in all imprinting control regions of certain samples.
- Findings suggested that somatic DNA contamination and genetic variations influence methylation studies in infertile men, complicating the results and interpretations regarding their fertility.
Article Synopsis
- The text discusses the challenges of analyzing whole genome bisulfite sequencing datasets due to the lack of comprehensive and reproducible workflows.
- The authors developed wg-blimp, an end-to-end pipeline that integrates various algorithms for tasks like alignment, quality control, and methylation analysis, requiring only raw data and a reference genome.
- They demonstrated wg-blimp's effectiveness by replicating published results from two datasets and applying it to embryonic stem cell samples, yielding consistent and reliable findings.
Article Synopsis
- - Angelman syndrome (AS) is a rare genetic disorder caused mainly by the loss of the UBE3A gene function, with a small percentage attributed to an imprinting defect affecting certain DNA regions.
- - Researchers analyzed the AS imprinting center (AS-IC) in 168 patients without deletions and found six common genetic variants, leading to five haplotypes, but no sequence alterations were detected.
- - In a study involving 119 families, they discovered that haplotype H-AS3, which contains a specific deletion, is significantly linked to an increased risk of the imprinting defect in AS patients, highlighting the importance of the AS-IC in genetic imprinting and disease development.
Article Synopsis
- - Transcriptional interference and read-through are key mechanisms in gene silencing and the establishment of DNA methylation, which impacts gene expression and can contribute to disease.
- - Researchers developed a cell culture system to investigate how transcriptional read-through influences gene repression and DNA methylation at specific human gene promoters.
- - Inducing transcriptional read-through led to consistent gene repression, regardless of promoter type, but did not result in DNA methylation, suggesting additional factors beyond transcription and DNA methyltransferases are necessary for methylation to occur.
Article Synopsis
- * Research found an additional repeat expansion site in the MARCH6 gene among European families, alongside previously identified expansions in the SAMD12 gene in Asia.
- * The study revealed significant variability in the size and structure of these repeat expansions and noted that large expansions can lead to genetic rearrangements in some cells, indicating a high level of instability.
The switch/sucrose non-fermenting (SWI/SNF) complex is an ATP-dependent chromatin remodeller that regulates the spacing of nucleosomes and thereby controls gene expression. Heterozygous mutations in genes encoding subunits of the SWI/SNF complex have been reported in individuals with Coffin-Siris syndrome (CSS), with the majority of the mutations in ARID1B. CSS is a rare congenital disorder characterized by facial dysmorphisms, digital anomalies, and variable intellectual disability.
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- The study investigates how the time between ovulation and fertilization affects the developmental capability of mouse oocytes and embryos, focusing on a specific chemical modification (H3K9me3) in the genome.
- It involved aging oocytes for different periods after retrieval and examining their development into early-stage embryos.
- Results showed that while the aging process did not impact the initial embryo development rates, it did lead to epigenetic changes that could affect later stages of embryo development.
Article Synopsis
- - Temple syndrome (TS14) is a rare genetic disorder linked to chromosome 14q32, resulting from abnormalities in gene imprinting that affect the expression of paternal and maternal genes differently.
- - A study of 13 TS14 patients showed that the imprinting defect can arise from either grandmaternal or grandpaternal inheritance, pointing to an issue that occurs during the paternal germ line's development after the normal imprinting process is erased.
- - The findings suggest that while many TS14 patients show a lack of methylation (gene silencing), some cases with mixed methylation patterns imply that these imprinting defects may originate from changes in early embryonic development rather than just genetic inheritance.
Article Synopsis
- Transgenerational epigenetic inheritance is the process where epigenetic information is passed down through generations, primarily via the germline.
- While this phenomenon is evident in organisms like plants, nematodes, and fruit flies, its presence in mammals, especially humans, is debated due to complexities involving genetic, ecological, and cultural factors.
- The text highlights the challenges researchers face in proving transgenerational epigenetic inheritance through experiments and observations, given these confounding influences.
Article Synopsis
- - Angelman syndrome (AS) is caused by genetic factors related to the 15q11q13 region, including chromosome deletions and mutations, with a focus on maternal inheritance patterns.
- - A study was conducted analyzing the chromosomal makeup of a child with AS and their parents, using advanced techniques to identify genetic abnormalities.
- - Findings indicated that the child has a normal chromosome structure but showed signs of uniparental disomy from the mother, likely resulting from a genetic error related to a specific chromosome rearrangement in the maternal lineage.
DNA methylation, i.e., the methylation of cytosine at carbon atom C5, has an important role in the regulation of gene expression.
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