Pharmacogenomic part 1

A rare and catastrophic event where a chromosome is shattered into hundreds of pieces, then haphazardly reassembled. This can result in gene fusions, deletions, and duplications.

Extrachromosomal DNA pieces, separate from the main chromosomes, that can carry amplified genes.

A gene that, when mutated, can contribute to the development of cancer. These genes frequently see increased expression due to chromothripsis and DMs.

A tumor suppressor gene critical for cell cycle control. Its loss often precedes chromothripsis, allowing cells to bypass crucial checkpoints and tolerate the DNA damage.

Clusters of point mutations, like a rain of genetic errors, often seen near DNA rearrangements. These mutations are much more frequent than background mutations.

A family of enzymes that are linked to the formation of kataegis. These enzymes can act as 'mutators,' increasing the frequency of mutations.

A gene that regulates cell cycle progression. It is often inactivated in pancreatic cancer due to chromothripsis, leading to uncontrolled cell growth.

A type of brain tumor where chromothripsis affects chromosome 11 in almost all cases. This event leads to the creation of a harmful fusion gene between RELA and C11orf95.

The presence or absence of a consistent relationship between age and mutations suggests that these mutations happen at different rates for different individuals, likely due to varying exposure to carcinogens or the onset of tumor growth.

The efficiency of DNA damage repair mechanisms can differ between the gene sequences being read by the cell's machinery (transcribed) and those that aren't (untranscribed). This difference is related to transcription-coupled nucleotide excision repair (TC-NER).

A specific pattern of mutations (Signature 4) linked to tobacco smoking in lung and liver cancers. It shows a preference for C/A mutations on the transcribed strand, likely because tobacco-induced DNA damage is eliminated through TC-NER.

Signature 7, often seen in malignant melanoma, has more C/T mutations on the untranscribed strand, consistent with UV damage and repair by TC-NER.

A specific pattern of mutations (Signature 6) characterized by C/T mutations at NpCpG sites and associated with a high number of substitutions and small indels (microsatellite instability). This signature indicates defects in DNA mismatch repair, a key process to fix errors during DNA copying.

This signature (Signature 15) also involves a lot of substitutions and small indels, but the specific types of mutations differ from Signature 6. It is observed in lung and stomach cancers.

Signature 3 is linked to larger deletions with overlapping microhomology and is strongly associated with mutations in genes BRCA1 and BRCA2, particularly in breast, ovarian, and pancreatic cancers. These genes are known to play a role in DNA repair mechanisms.

Mutational signatures are patterns of mutations in DNA that can be unique to different cancers. They are influenced by factors like the type of cancer, the cause of the mutations, and the effectiveness of DNA repair mechanisms.

A method for identifying methylation patterns in DNA by selectively cutting unmethylated regions with restriction enzymes and sequencing the resulting fragments.

A technique that enriches for methylated DNA fragments, allowing for the identification of methylation patterns across the genome.

Regions in the genome where methylation is less common, often associated with gene regulation.

Regions in the genome where methylation is more common, often associated with gene silencing.

A process that transforms DNA fragments into sequencing libraries, allowing for analysis by NGS technologies.

A family of enzymes used in MRE-seq that selectively cut unmethylated DNA at specific recognition sites.

A technique for analyzing methylation patterns by sequencing DNA, often using Illumina platforms.

Using bioinformatics tools to align sequenced reads to the reference genome, identify unmethylated regions, and analyze differential methylation patterns.

A chemical modification of DNA where a methyl group is added to the fifth carbon of cytosine, usually at CpG dinucleotides. This modification plays a vital role in regulating gene expression and maintaining epigenetic patterns.

Clusters of CpG dinucleotides in DNA that are typically unmethylated. These regions are often associated with active gene expression.

A family of enzymes critical for catalyzing the addition of methyl groups to DNA, establishing and maintaining methylation patterns. They are involved in epigenetic regulation, gene silencing, and development.

The major form of DNA modification in mammals where a methyl group is attached to the fifth carbon of cytosine. It plays significant roles in regulating gene expression, silencing repetitive elements, and maintaining genomic stability.

A process where DNA methylation patterns are maintained during DNA replication, ensuring daughter cells inherit the epigenetic information from their parent cells.

A key function of DNA methylation that generally leads to gene silencing. It can affect DNA binding by proteins, promote the binding of methyl-binding proteins, and change chromatin structure.

A protein that binds to methylated DNA and plays a role in gene repression and chromatin remodeling.

A specific DNMT responsible for copying existing methylation patterns during DNA replication, ensuring that new DNA strands inherit the original methylation profile.

A specific type of DNA methylation where a cytosine base is modified with a hydroxyl group, creating 5-hydroxymethylcytosine. This modification is often associated with active DNA demethylation.

A sequencing technique that utilizes modified enzymes to detect 5-hydroxymethylcytosine (5hmC) directly in DNA, without needing chemical treatments. Provides a comprehensive map of 5hmC distribution across the genome.

A high-throughput sequencing technology that specifically focuses on mapping 5-carboxylcytosine (5caC), an intermediate in the active demethylation pathway. It helps understand DNA demethylation dynamics and regulatory elements.

A specialized sequencing technology that generates longer DNA sequences compared to traditional methods. It allows for the analysis of complex genomic regions, including repetitive sequences and structural variations.

A specialized type of sequencing technology that allows the identification of DNA methylation directly during the sequencing process, without needing separate analysis. It can detect various methylation modifications, such as 5mC and 5hmC.

A series of computational steps used to analyze long-read sequencing data, including error correction, alignment, methylation calling, and downstream analysis. It produces a detailed map of methylation patterns and reveals insights into gene regulation.

A computational tool used for aligning long reads, typically from Nanopore sequencing, to a reference genome. It excels in handling complex regions and is capable of accurately identifying methylation modifications.

The process of converting 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) and further oxidation to 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC), ultimately leading to DNA demethylation. This process is essential for various biological events like embryonic development and cell differentiation.

A family of enzymes responsible for catalyzing the oxidation of 5-methylcytosine (5mC) in DNA into 5-hydroxymethylcytosine (5hmC). They are primary players in the active DNA demethylation pathway.

Mutations in IDH1 and IDH2 genes can lead to the accumulation of an abnormal metabolite, which promotes hypomethylation, contributing to the development of glioblastoma.

TET enzymes can play a role in gene repression. This non-catalytic function is less understood but thought to act in opposition to the catalytic function.

During early embryonic development (fertilization to implantation), both parental genomes undergo significant epigenetic reprogramming, characterized by extensive DNA demethylation.

The paternal genome's demethylation primarily involves a combination of passive dilution and active TET3-mediated modifications.

The maternal genome's demethylation in early embryogenesis is mainly achieved through passive dilution.

DNA methylation alterations can lead to changes in gene expression, potentially affecting embryonic development, postnatal growth, and placental function, even in the absence of genetic mutations.