M1-Lecture3 Flashcards
Epigenetics and Health
DNA does not change throughout development or during adulthood - other than acquired mutations - including germline changes, epigenetic changes? T/F
True
Epigenetics tags arise during development of fetus as cells & tissues differentiate? T/F
True
Some genes can be turned on or off with epigenetic tags permanently or as needed? T/F
True
Three basic epigenetic marks that control gene expression, mention>.
DNA methylation, histone modification and non-coding RNAs.
Unlike DNA, epigenetic tags can be modified throughout life both in negative and positive ways with diet & environmental exposures. T/F
True
Epigenetic marks during embryonic development & programming state the roles:
Erasure & establishment of DNA methylation marks, genetic imprinting, X-chromosome inactivation, the development of pluripotent stem cells & differentiation of somatic cells.
Immediately following fertilization, paternal genome undergoes rapid methylation & histone modifications through active & passive mechanisms. T/F
True
What is demethylated gradually - new wave of embryonic methylation that establishes the blueprint for tissues of developing embryo? T/F
Maternal genome, True
The de novo DNA methyltransferase enzymes, DNMT3a & DNMT3b, restore DnA methylation beginning from blastocyst stage? T/F
True
Each cell has its own epigenetic pattern? T/F
True
When do maternal & paternal genome combine in the same cell and DNA methylation and reprogramming occur to erase epigenetic patterns to establish totipotent state.
After fertilization
Although after fertilization, paternal & maternal combine and DNA pattern is erased, some genes remain “imprinted” with methyl marks (parent of origin) & maintained throughout the life of the offspring. T/F
True
Define imprinted genes?
Genes whose expression is determined by the parent that contributed them.
How do imprinted genes violate the rule of inheritance?
Both alleles in a heterozygote are equally expressed, but not in this case. One gene may be silenced based on parental origin.
Assisted reproduction or cloning may impose inherent risks to normal development? T/F
True
Cloning experiments procedure:
Nucleus of somatic cell must be reprogrammed to epigenetic state of an embryonic nucleus.
Genes in somatic cells must be silenced, while those needed for embroynic deve. must be activated.
Epigenetic defects may indicate that donated nucleus is not efficiently programmed.
During cloning how to ensure the egg does not contribute any genetic material?
By removing the nucleus
During cloning, why does the egg come from a different sheep?
To minimize immune system reaction. The immune system is less likely to react to an egg from a different sheep b/c it’s not familiar with proteins & signals present in the egg. It’s less prone to identifying it as “self” - lower chance of immune response.
What have been viewed as an attractive tool to prevent pediatric developmental diseases and cancer as well to delay aging-associated processes?
Nutritional epigenetics
Gene silencing through targeted nutrition allows epigenetic mechanisms of action to prevent or delay onset of inherited health problems and improve quality of life. T/F
True
Nutrition and environmental factors affect epigenetic inheritance of future generations? T/F
True
What is the study of food & food constituents on gene expression.
Nutrigenomics
Mentions a few examples as to how mutations affect how we process food:
PKU, lactose intolerance,
Alcohol flush reaction (mutation in gene impair processing of alcohol) resulting in skin flushing & intoxication.
Animal studies show that A diet with too little methyl-donating folate or choline BEFORE OR AFTER (long-term deficiency) birth causes certain regions of genome to be under-methylated for life. T/F
True
And for adults too, methyl-deficient diet leads to decrease in DNA methylation, but changes are reversible when methyl is added back to diet. T/F
True
Three factors that influence gut microbiota:
Maternal factors:
Maternal nutrition
Embryonic environment
Mode of delivery
Dietary patterns:
Breast feeding/formula diet
Diet enriched with fruits & vegetables/western diet
Environmental factors:
Lifestyle
Hygiene
Drugs/antibiotic exposure
Exercise
Geography
Host genetics
One-size-fits-all nutrition are inefficient & often ineffective. T/F
True b/c does not account for individual differences in needs and responses.
What can explain why same foods affect people differently?
Nutrigenomics
Proper nutrition can decrease risk of developing chronic diseases? T/F
True
What familiar nutrients are key components of methyl-making pathway?
Folic acid, B vitamins, SAM-e (S-Adensoyl methionine)
Today, more than 95% of chronic diseases are caused by food choice. T/F
True
Epigenetic changes can occur before, during, or after t he onset of a disease? T/F
True
Some epigenetic modifications can be reversible? T/F
True
What are the non-genetic factors besides epigenetics that affect the risk of T2DM?
Obesity, unhealthy diet, physical inactivity, ageing & intrauterine environment.
Obesity, unhealthy diet, physical inactivity, ageing & intrauterine environment. These have been associated with epigenetic modifications in healthy individuals? T/F
True
Epigenetic changes in the Islets of Langerhans of the pancreas can be detected in patients many years before diagnosis of type 2 diabetes. T/F
True
Mention epigenetic modifications in type 2 diabetes:
Altered DNA methylation in pancreatic islets, adipose tissue, skeletal muscle & liver from those with t2DM.
Epigeentic marks can be used as biomarkers for prediction of T2DM, risk of vascular complications, response to therapy & lifestyle interventions. T/F
True
Precision of medicine
What’s caused by abnormality in the FMR1 (fragile X mental retardation 1) gene.
The Fragile X syndrome
6 to 50 repeats of trinucleotide CGG means not having fragile x syndrome,. But with over 200 repeats, they have full mutation? True
True
The mechanism that leads to fragile x syndrome:
Too many CGGs cause CpG islands at promoter region of the FMR1 gene to become methylated; normally they are not. It turns genes off.
Many of mental health conditions have both genetic and epigenetic modifications that contribute to disease? T/F
True
Fragile X syndrome is the only disorder associated with mental retardation that involves epigenetic changes. T/F
True
Mention other X-linked disorders.
Schizophrenia shows high degree of heritability: T/F
True
Studies show association between schizophrenia & mood disorders with what and the gene(s)?
DNA rearrangements that include DNMT genes.
What is overexposed in in GABA-ergic interneurons of schizophrenic brains. T/F
DNMT1
DNA methylation in genes of neural development & neurotransmission is found.
True
In mice, great association btw. antidepressant drugs and epigenetic modifications. T/F
True
Both genetic factors and environmental factors affect epigenome, which affect schizophrenia: T/F
True
Positive symptoms of schizo:
Hallucination
Delusions
Negative symptoms of schizo:
Social withdrawal
Apathy
Anhedonia
Cognitive dysfunction of schizo:
Attention & working memory
Genetic factors that affect epigenetic alterations that contribute to schizophrenia:
COMT
DTNBP1
NRG1
Environmental factors that affect epigenetic alterations that contribute to schizophrenia:
Stress
Viral infection
The result of environmental and genetic factors in epigenetic alterations in the development of shizophrenia:
Hypermethylation of RELN
Hypermethylation of SOX10
Hypomethylation of COMT
What is a neurodegenerative disease with unknown pathogenesis & complex pathological manifestations:
AD
Name the main manifestation of AD:
Extraneuronal amyloid plaque (Abeta) deposition & intracellular neurofibrillary tangles (NFTs)
Stress is an important environmental factor: T/F
True
Stress, PTSD, abused exhibit varying levels of DNA methylation and gene expression in comparison. T/F
True
Epigenetic alterations can contribute to the development of autoimmune diseases? T/F & how
True
Epigenetic dysregulation/loss of epigenetic control is the factor b/c it regulates immune cell functions. And environmental factors cann induce epigenetic changes.
How does epigenetic regulate immune system:
Shifts in acetylation & methylation allow DNA accessibility & permit recombination resulting in cells to produce immune response against a particular antigen.
What is shown to be a success in prevention of neural tube defects, but can be linked to allergic airway diseases.
Folate supplements
Blank is a chronic autoimmune dysfunction - due to development of autoantibodies against nuclear antigens, which affects any organ system & tissue like kidney & blood vessels.
SLE
Neutrophils & granulocytes from patients with SLE are described as hypomethylated, especially at gene locus of MX1 & IFI44L.
Yes
SLE is most studied autoimmune disease linked with epigenetic modification.
yes
SLE occurs in women and is caused by dysregulation of T lymphocytes. T/F
True
What is chronic & debilitating inflammatory sickness that causes arthritis?
RA
Epigenetic mechanisms in RA:
Altered methylation in T & B cells, including synovial fibroblasts.
Studies show that RA patients’ T cells had remarkable phenotype, similar to SLE, hypomethylation.
Yes
Is methotrexate (MTX) is used to treat RA:
Yes
But MTX can lead to the accumulation of Treg cells by inducing FOXP3 expression through promoter demethylation. T/F
True
DNa hypermethylation negative impact:
Initiates silencing of tumor suppressor genes
genes of colorectal cancer with hypomethylated compared to normal tissues. T/F
True
Modifications in DNA methylation patterns due to PA can increase expression of genes like tumor suppressor & decrease expression of oncogenes. T/F
True
DNA hypomethylation negative impact:
Activate oncogenes
Initiate chromosome instability
Progeria, also known as Hutchinson-Gilford Progeria Syndrome (HGPS), is a rare genetic disorder characterized by accelerated aging in children. T/F
True
Gene promoters become hypermethylated as an individual ages?
Yes
CpG sequences of non-coding centromeric repeats become hypomethylated with age?
Yes
Many known age-related DNA methylation are associated with disease. T/F
True
Mammalian sirtuin protein family (SIRT1-SiRT7) regulatory role:
In metabolism (fat & glucose) in response to physiological changes in energy levels that controls homeostasis & Ageing
Sirutins deacetylate histones & several transcriptional regulators in the nucleus, in cytoplasm, mitochondria. T/F
True
What are the most promising targets for ant-ageing approaches:
Belonging to the sirutin family
Sirtuins are NAD+ dependent histone deacetylases regulating important metabolic pathways in prokaryotes & eukaryotes. T/F
True
Sirutins are involved in many biological processes, such as:
Cell survival, senescence , proliferation, apoptosis, DNA repair, cell meta., and caloric restriction.
Three families of epigenetic proteins -
Readers, writers, erasers
Can be addressed through small -molecule inhibitors.
Now epigenetic based drugs are non-specific. T/F
True
Review epigenetic medications
The first wave of epigenetic drugs:
DNA methyltransferase inhibitors (Ex. azacitidine and decitabine)
Histone deacetylase inhibitors (trichostatin A and trapoxin)
