Epigenetics in the context of PCNA

In botany, a sport or bud sport, traditionally called lusus, is a part of a plant that shows morphological differences from the rest of the plant. Sports may differ by foliage shape or color, flowers, fruit, or branch structure. The cause is generally thought to be chance genetic mutations in a single cell. Sports may also arise from stable changes in gene expression due to epigenetic modifications, including histone modification, DNA methylation, chromatin remodeling and RNA silencing. If the clonal descendants of a modified cell eventually form a meristem that gives rise to new plant parts, those may be of a new phenotype. Often only part of the meristem cells are affected, resulting in genetic chimerism in such sports.

Cellular differentiation is the process in which a stem cell changes from one type to a differentiated one. Usually, the cell changes to a more specialized type. Differentiation happens multiple times during the development of a multicellular organism as it changes from a simple zygote to a complex system of tissues and cell types. Differentiation continues in adulthood as adult stem cells divide and create fully differentiated daughter cells during tissue repair and during normal cell turnover. Some differentiation occurs in response to antigen exposure. Differentiation dramatically changes a cell's size, shape, membrane potential, metabolic activity, and responsiveness to signals. These changes are largely due to highly controlled modifications in gene expression and are the study of epigenetics. With a few exceptions, cellular differentiation almost never involves a change in the DNA sequence itself. Metabolic composition, however, gets dramatically altered where stem cells are characterized by abundant metabolites with highly unsaturated structures whose levels decrease upon differentiation. Thus, different cells can have very different physical characteristics despite having the same genome.

A specialized type of differentiation, known as terminal differentiation, is of importance in some tissues, including vertebrate nervous system, striated muscle, epidermis and gut. During terminal differentiation, a precursor cell formerly capable of cell division permanently leaves the cell cycle, dismantles the cell cycle machinery and often expresses a range of genes characteristic of the cell's final function (e.g. myosin and actin for a muscle cell). Differentiation may continue to occur after terminal differentiation if the capacity and functions of the cell undergo further changes.

Genetics is the study of genes, genetic variation, and heredity in organisms. It is an important branch in biology because heredity is vital to organisms' evolution. Gregor Mendel, a Moravian Augustinian friar working in the 19th century in Brno, was the first to study genetics scientifically. Mendel studied "trait inheritance", patterns in the way traits are handed down from parents to offspring over time. He observed that organisms (pea plants) inherit traits by way of discrete "units of inheritance". This term, still used today, is a somewhat ambiguous definition of what is referred to as a gene.

Trait inheritance and molecular inheritance mechanisms of genes are still primary principles of genetics in the 21st century, but modern genetics has expanded to study the function and behavior of genes. Gene structure and function, variation, and distribution are studied within the context of the cell, the organism (e.g. dominance), and within the context of a population. Genetics has given rise to a number of subfields, including molecular genetics, epigenetics, population genetics, and paleogenetics. Organisms studied within the broad field span the domains of life (archaea, bacteria, and eukarya).

Genetic predisposition refers to a genetic characteristic which influences the possible phenotypic development of an individual organism within a species or population under the influence of environmental conditions. The term genetic susceptibility is often used synonymously with genetic predisposition and is further defined as the inherited risk for specific conditions, based on genetic variants. While environmental factors can influence disease onset, genetic predisposition plays a role in inherited risk of conditions, such as various cancers. At the molecular level, genetic predisposition often involves specific gene mutation, regulatory pathways, or epigenetic modifications that alter cellular processes, increasing disease risk.

The Punnett square is a square diagram that is used to predict the genotypes of a particular cross or breeding experiment. It is named after Reginald C. Punnett, who devised the approach in 1905. The diagram is used by biologists to determine the probability of an offspring having a particular genotype. The Punnett square is a tabular summary of possible combinations of maternal alleles with paternal alleles. These tables can be used to examine the genotypical outcome probabilities of the offspring of a single trait (allele), or when crossing multiple traits from the parents.

The Punnett square is a visual representation of Mendelian inheritance, a fundamental concept in genetics discovered by Gregor Mendel. For multiple traits, using the "forked-line method" is typically much easier than the Punnett square. Phenotypes may be predicted with at least better-than-chance accuracy using a Punnett square, but the phenotype that may appear in the presence of a given genotype can in some instances be influenced by many other factors, as when polygenic inheritance and/or epigenetics are at work.

Single-cell sequencing examines the nucleic acid sequence information from individual cells with optimized next-generation sequencing technologies, providing a higher resolution of cellular differences and a better understanding of the function of an individual cell in the context of its microenvironment. For example, in cancer, sequencing the DNA of individual cells can give information about mutations carried by small populations of cells. In development, sequencing the RNAs expressed by individual cells can give insight into the existence and behavior of different cell types. In microbial systems, a population of the same species can appear genetically clonal. Still, single-cell sequencing of RNA or epigenetic modifications can reveal cell-to-cell variability that may help populations rapidly adapt to survive in changing environments.

Carcinogenesis, also called oncogenesis or tumorigenesis, is the formation of a cancer, whereby normal cells are transformed into cancer cells. The process is characterized by changes at the cellular, genetic, and epigenetic levels and abnormal cell division. Cell division is a physiological process that occurs in almost all tissues and under a variety of circumstances. Normally, the balance between proliferation and programmed cell death, in the form of apoptosis, is maintained to ensure the integrity of tissues and organs. According to the prevailing accepted theory of carcinogenesis, the somatic mutation theory, mutations in DNA and epimutations that lead to cancer disrupt these orderly processes by interfering with the programming regulating the processes, upsetting the normal balance between proliferation and cell death. This results in uncontrolled cell division and the evolution of those cells by natural selection in the body. Only certain mutations lead to cancer whereas the majority of mutations do not.

Variants of inherited genes may predispose individuals to cancer. In addition, environmental factors such as carcinogens and radiation cause mutations that may contribute to the development of cancer. Finally random mistakes in normal DNA replication may result in cancer-causing mutations. A series of several mutations to certain classes of genes is usually required before a normal cell will transform into a cancer cell. Recent comprehensive patient-level classification and quantification of driver events in TCGA cohorts revealed that there are on average 12 driver events per tumor, of which 0.6 are point mutations in oncogenes, 1.5 are amplifications of oncogenes, 1.2 are point mutations in tumor suppressors, 2.1 are deletions of tumor suppressors, 1.5 are driver chromosome losses, 1 is a driver chromosome gain, 2 are driver chromosome arm losses, and 1.5 are driver chromosome arm gains. Mutations in genes that regulate cell division, apoptosis (cell death), and DNA repair may result in uncontrolled cell proliferation and cancer.

Piwi-interacting RNA (piRNA) is the largest class of small non-coding RNA molecules expressed in animal cells. piRNAs form RNA-protein complexes through interactions with piwi-subfamily Argonaute proteins. These piRNA complexes are mostly involved in the epigenetic and post-transcriptional silencing of transposable elements and other spurious or repeat-derived transcripts, but can also be involved in the regulation of other genetic elements in germ line cells.

piRNAs are mostly created from loci that function as transposon traps which provide a kind of RNA-mediated adaptive immunity against transposon expansions and invasions. They are distinct from microRNA (miRNA) in size (26–31 nucleotides as opposed to 21–24 nt), lack of sequence conservation, increased complexity, and independence of Dicer for biogenesis, at least in animals. (Plant Dcl2 may play a role in rasi/piRNA biogenesis.)

Conrad Hal Waddington CBE FRS FRSE (8 November 1905 – 26 September 1975) was a British developmental biologist, paleontologist, geneticist, embryologist and philosopher who laid the foundations for systems biology, epigenetics, and evolutionary developmental biology.

His theory of genetic assimilation probably has a Darwinian explanation, which contrast with the fact that Waddington himself was very critic about the notion of natural selection and Neo-Darwinism. Leading evolutionary biologists including Theodosius Dobzhansky and Ernst Mayr considered that Waddington was using genetic assimilation to support so-called Lamarckian inheritance, the acquisition of inherited characteristics through the effects of the environment during an organism's lifetime.

Immunological memory is the ability of the immune system to quickly and specifically recognize an antigen that the body has previously encountered and initiate a corresponding immune response. Generally, they are secondary, tertiary and other subsequent immune responses to the same antigen. The adaptive immune system and antigen-specific receptor generation (TCR, antibodies) are responsible for adaptive immune memory.

After the inflammatory immune response to danger-associated antigen, some of the antigen-specific T cells and B cells persist in the body and become long-living memory T and B cells. After the second encounter with the same antigen, they recognize the antigen and mount a faster and more robust response. Immunological memory is the basis of vaccination. Emerging resources show that even the innate immune system can initiate a more efficient immune response and pathogen elimination after the previous stimulation with a pathogen, respectively with PAMPs or DAMPs. Innate immune memory (also called trained immunity) is neither antigen-specific nor dependent on gene rearrangement, but the different response is caused by changes in epigenetic programming and shifts in cellular metabolism. Innate immune memory was observed in invertebrates as well as in vertebrates.

Nuclear organization refers to the spatial organization and dynamics of chromatin within a cell nucleus during interphase. There are many different levels and scales of nuclear organization.

At the smallest scale, DNA is packaged into units called nucleosomes, which compacts DNA about 7-fold. In addition, nucleosomes protect DNA from damage and carry epigenetic information. Positions of nucleosomes determine accessibility of DNA to transcription factors.

In the history of biology, preformationism (or preformism) is a formerly popular theory that organisms develop from miniature versions of themselves. Instead of assembly from parts, preformationists believed that the form of living things exist, in real terms, prior to their development. Preformationists suggested that all organisms were created at the same time, and that succeeding generations grow from homunculi, or animalcules, that have existed since the beginning of creation, which is typically defined by religious beliefs.

Epigenesis (or neoformism), then, in this context, is the denial of preformationism: the idea that, in some sense, the form of living things comes into existence. As opposed to "strict" preformationism, it is the notion that "each embryo or organism is gradually produced from an undifferentiated mass by a series of steps and stages during which new parts are added" (Magner 2002, p. 154). This word is still used in a more modern sense, to refer to those aspects of the generation of form during ontogeny that are not strictly genetic, or, in other words, epigenetic.

A cancer biomarker refers to a substance or process that is indicative of the presence of cancer in the body. A biomarker may be a molecule secreted by a tumor or a specific response of the body to the presence of cancer. Genetic, epigenetic, proteomic, glycomic, and imaging biomarkers can be used for cancer diagnosis, prognosis, and epidemiology. Ideally, such biomarkers can be assayed in non-invasively collected biofluids like blood or serum.

While numerous challenges exist in translating biomarker research into the clinical space; a number of gene and protein based biomarkers have already been used at some point in patient care; including, AFP (liver cancer), BCR-ABL (chronic myeloid leukemia), BRCA1 / BRCA2 (breast/ovarian cancer), BRAF V600E (melanoma/colorectal cancer), CA-125 (ovarian cancer), CA19.9 (pancreatic cancer), CEA (colorectal cancer), EGFR (Non-small-cell lung carcinoma), HER-2 (Breast Cancer), KIT (gastrointestinal stromal tumor), PSA (prostate specific antigen) (prostate cancer), S100 (melanoma), and many others. Mutant proteins themselves detected by selected reaction monitoring (SRM) have been reported to be the most specific biomarkers for cancers because they can only come from an existing tumor. About 40% of cancers can be cured if detected early through examinations.

Molecular neuroscience is a branch of neuroscience that observes concepts in molecular biology applied to the nervous systems of animals. The scope of this subject covers topics such as molecular neuroanatomy, mechanisms of molecular signaling in the nervous system, the effects of genetics and epigenetics on neuronal development, and the molecular basis for neuroplasticity and neurodegenerative diseases. As with molecular biology, molecular neuroscience is a relatively new field that is considerably dynamic.

Genomic imprinting is an epigenetic phenomenon that causes genes to be expressed or not, depending on whether they are inherited from the female or male parent. Genes can also be partially imprinted. Partial imprinting occurs when alleles from both parents are differently expressed rather than complete expression and complete suppression of one parent's allele. Forms of genomic imprinting have been demonstrated in fungi, plants and animals. In 2014, there were about 150 imprinted genes known in mice and about half that in humans. As of 2019, 260 imprinted genes have been reported in mice and 228 in humans.

Genomic imprinting is an inheritance process independent of the classical Mendelian inheritance. It is an epigenetic process that involves DNA methylation and histone methylation without altering the genetic sequence. These epigenetic marks are established ("imprinted") in the germline (sperm or egg cells) of the parents and are maintained through mitotic cell divisions in the somatic cells of an organism.