Nutrigeneomics Past Paper PDF

Klausurfragen Nutrigeneomics Vorlesung NGG is defined as the science that explains the effect of genetic variation an dietary response. Richtig Allelic mutations are always associated with mesureable traits (pehenotypes). Richtig Novel genes are protein-coding DNA sequences with unkown function. Ric...

Klausurfragen Nutrigeneomics Vorlesung NGG is defined as the science that explains the effect of genetic variation an dietary response. Richtig Allelic mutations are always associated with mesureable traits (pehenotypes). Richtig Novel genes are protein-coding DNA sequences with unkown function. Richtig The term “genomics” refers to the amount, genetic locations, structures and function of genes. Richtig The basic/ fundamental research deals with early biomarkers to predict the onset of diseases. Falsch → knock-out reactions as basic research methods, not biomarkers which are more common in applied sciences. Also, biomarkers are not sufficient to predict onset of diseases. Alzheimer (AD) Parkinson (PD) neurocortex Substancia nigra Alpha-Beta-plaques required Mutations→ amyloid precusorgenes on the Mutations splice and cleavage site → alpha-synuclein loss of function mutation ➔ Overexpression + cell death leads to missfolding + aggregation → Lewy-bodies →PARKIN →PINK1 (mitochondria health) →promotorregion of alpha-synuclein leidas to overexpression ➔ Cell death Other proteins downstream can also be involved bc these mutations can´t explain all Nutrigenomics deal with DNA sequence variants that have an influence nutrition related diseases. Richtig Type II diabetes is closely linked to insulin resistance, overweightness. Richtig The loss of IR by mutation impairs the ability of insulin to stimulate glucose uptake in cells. Richtig Loss-of-function mutations along the insulin signaling pathway improve the insulin sensitivity. Falsch→ not improve The loss of IR by mutation mimics a reduced intake of glucose or carbohydrates from foods. Richtig Nutritional phenotypes do not have an influence on cellular signaling. Richtig Model organisms are not suitable for the analysis of nutritional phenotypes associated with human diseases. Falsch Nutritional phenotypes are established in life science as disease models. Richtig mTOR activity can be inhibited by caloric restriction. Richtig Transcription factors are specific proteins which promote de expression of genes. Richtig Transcription Factors of PPAR and SREBP family act downstream of mTOR in lipogenesis. Richtig All types of adipocytes or cells in general exhibit gene expression pattern which are identical. Falsch An allele is always associated with a phenotype. Richtig The mTOR/TOR complex is evolutionary well conserved across species. Richtig The AMPK acts to inhibit insulin signaling and to promote mTOR activity. Falsch→ not promote Energy rich substrates inhibit the activity of the AMPK Richtig Adenosine triphosphate (AKP) activates the AMPK. Falsch→ not inhibit The AMPK acts as an energy sensor in cells. Richtig Branched chain amino acids (BCAAs) can inhibit the imTOR complex. Falsch→ not inhibit (m)TOR is activated by insulin to induce anabolic processes Richtig (m)TOR deficiency mimics caloric restriction in ad libitum fed model organisms. Richtig Allelic mutations can be used as a method to investigate the functions of genes. Richtig The pathogenesis of T2DM is driven by a systemic dysregulation of IRS) and IRS2. Richtig During T2DM fatty acids are produced in excess, because glucose needs to be replaced as basto source of onergy. Richtig Many studies support the theory, that the signal transduction along the ins pathway is non- linear. Richtig Systemic IR- or IRS-knockout organisms can mimic the systemic phenotypes of T2DM. Richtig Systemic IR- or IRS-knockout organisms can mimic the tissue-specific metabolism of T2DM. Flasch→ systemic has systemic effects not tissuespecific Selective tissue-specific IR-or IRS-knockouts can mimic the tissue-specific metabolism of T2DM Richtig Genetic screens are powerful tools used for the identification of genes and their functions. Richtig Suppressor screens are used for the identification of genes active in distinct pathways. Falsch→ only members of the same signalingpathway! Novel genes can be detected by forward-genetic screens. Richtig Forward-genetic approaches are based on random mutagenesis. Richtig Reverse-genetic approaches include random mutagenesis on the sequence of already known genes. Richtig Genetic complementation is a reverse-genetic tool. Richtig Genetic complementation implicates the expression of a mutated gene in the corresponding wildtype organism. Flasch→ wildtype in mutated gene Genetic complementation implicates the expression of a wildtype gene in the corresponding mutant background. Richtig A gene knock-down causes a more or less pronounced rest activity of the affected protein. Richtig A gene knock-out causes a complete loss of function in the affected protein. Richtig Knock-out alleles generate softer phenotypes then most knock-down variants of the same gene. Flasch→ Knock-down generates softer phenotypes; Knock-out results in lethal phenotype Genetic complementation can be performed systemically or tissue-specific. Richtig A-tissue-specific genetic complementation requires a tissue-specific promoter sequence. Richtig Epigenetic modifications on the DNA are SNPs, insertions or deletions. Falsch Like caloric restriction, BCAA can reduce the activity mTOR complex. Falsch→ not reduce (m)TOR deficiency mimics caloric restriction in ad libitum fed model organisms. Richtig Reduced insulin (like) signaling and/or dietary restriction induce lifespan extension. Richtig The inhibition of mTOR activates the TF FOXO. Falsch → not directly FOXO deficiency mimics caloric restriction in ad libitum fed model organisms. Falsch→ not deficiency An active FOXO 1 induces lifespan extension in many species. Richtig Some components of the DR pathway function in parallel to mTOR signaling (additive effects). Richtig Knockdown of mTOR and/or treatment with Rapamycin can mimic DR in model organisms Richtig (m)TOR deficiency mimics caloric restriction in ad libitum fed model organisms. Richtig The inhibition of mTOR and AKT activates the TF FOXO-1. Falsch→ not directly An active FOXOA3 is associated with lifespan extension in humans. Richtig mTOR activity can be inhibited by CR. Richtig Some components of the CR pathway function in parallel to mTOR generating additive effects on lifspan. Richtig The APO-isoforms e2 / e2 and e2 / e3 are associated with reduced cardiovascular risk and improved health span. Richtig The APO-isoform c4 / e4 cause an increased risk of death below the age reached by less than 1% of an population. Richtig Mutations that influence the specific functions of APOE are located at the AA 112 and 158 in the protein. Richtig The FOXOA1 variant increases the lifespan when combined with combined with social behavioural factors. Richtig All FOXO3A variants were found more frequent in centenarians than in 90 years old humans. Richtig The answer on the question, whether a mutation or a nutritional condition can cause an effect along the insulin signaling pathway (ISP) which is adverse or rather beneficial strongly depends on how strong/drastic the mutation or the nutritional intervention is. Richtig Mild caloric restriction or weak loss of function mutations along the ISP induce increased (regular) fat storage and an extension of the lifespan. Richtig Drastic caloric restriction (starvation) or knockout mutations along the ISP induce increased (ectopic) fat storage and severe T2DM. Richtig Neurodegenerative diseases are characterized by the loss of specific brain neurons activity. Richtig The pathogenesis of Alzheimer's disease (AD) starts in the brain area called substatia nigra. Falsch→ Parkinson Parkinson's disease (PD) shows motor neuron alteration, tremors, and loss of muscular strength. Richtig The pathogenesis of PD starts in the brain areas called Hippocampus and Cortex. Falsch→ Alzheimer AD involves the deposition of senile plaques extracellularly which are comprised of ẞ- amyloid (AB). Richtig Both AD and PD have been shown to be a result of abnormal protein accumulation and aggregation. Richtig In brain cells of individuals with AD, a-synuclein can gather in clumps called Lewy bodies. Richtig → also/ more in PD FOXO TFs are required for the maintenance of autophagy and survival of neurons during aging. Richtig Alzheimer's disease genotypes include mutated SNCA, PINKI, and/or PARK genes. Falsch → Parkinson Loss-of-function mutations in the cleavage sites of APP induce increased production and aggregation of AB. Richtig The extracellular accumulation of AB is sufficient for the pathogenesis of Falsch→ required, but not sufficient. Sufficeint is TAU-Proteinhypaerphosphorylation due to MAPkinase mediated processes activated by ROS Most proteins require ubiquitinilation before their degradation in the proteasome. Richtig Insulin resistance, mitochondrial functions, and neurodegenerative diseases are strongly associated. Richtig Active FOXO3 induces degradation of toxins (misfolded a-synuclein) by increasing expression of mitochondrial E3 ubiquitin ligases. Richtig Suppression of the PI3K-Akt-mTOR signalling by CR increased the expression of PARKIN and PINKI in human and mouse neurons. Richtig→ Insulin-signalling pathway Autophagy is an evolutionarily conserved process that allows cells to degrade and recycle cytoplasmic proteins and organelles. Richtig Long term CR significantly reduced the cerebral amyloid expression and deposition in human hippocampal neurons and animal models. Richtig FOXO factors inhibit the ubiquitin-proteasome clearance system on the transcriptional level. Falsch → not inhibit The insulin signaling system acts upstream of the ubiquitin-proteasome clearance system. Richtig The metabolic syndrome accelerates the progression of neurodegenerative phenotypes. Richtig The insulin signaling pathway has a major impact on neurodegenerative phenotypes, longevity, and diseases determined by the metabolic syndrome. Richtig Nutrigenomics deal with the identification of DNA sequence variants that influence the onset and/or progression of nutrition related diseases. Richtig Type II diabetes is closely linked to insulin resistance and overweightness. drastic mutation Richtig Loss-of-function mutations along the insulin signaling pathway improve the insulin sensitivity. Falsch The loss of IRSI by mutation impairs the ability of insulin to stimulate glucose uptake and GLUT translocation. Richtig All types of cells exhibit the same gene expression pattern. Falsch An allele is always associated with a phenotype. Richtig The AMPK inhibits insulin signaling and promotes an increased mTOR activity. Flasch→ not increased Energy rich substrates inhibit the AMPK activity in favor of energy storage. BCAAs can inhibit the activity of mTOR. Richtig→ Due to mTOR mTOR deficiency mimics caloric restriction in ad libitum fed model organisms. Richtig The pathogenesis of T2DM is driven by a systemic dysregulation of IRSI and IRS2. Richtig During T2DM fatty acids are produced in excess, because glucose needs to be replaced as basic source of energy. Richtig→ although glucose cannot really be replaced in some cells Many studies support the theory, that the signal transduction along the ins. pathway is non- linear. Richtig Systemic IR- or IRS-knockout organisms can mimic the tissue specific metabolism of T2DM. Falsch→ systemic has no tissuespecific impact Novel genes can be detected in forward-genetic screens. Richtig Forward-genetic approaches are based on random mutagenesis. Richtig Genetic complementation is a reverse-genetic tool. Richtig Genetic complementation uses the expression of a wildtype gene in the corresponding mutant backround. Richtig A gene knock-out causes complete loss of function in the affected protein. Richtig Genetic complementation can be performed systemically or tissuespecific. Richtig→ depending on promotor sequenz (universal or tissuespecific) (m)TOR deficiency mimics caloric restriction in ad libitum fed model organisms. Richtig Reduced insulin (like) signaling and/or dietary restriction induce lifespan extension. Richtig FOXO deficiency mimics caloric restriction in ad libitum fed model organisms. Flasch Active FOXO TFs induce lifespan extension in many species. Richtig The inhibition of mTOR and AKT activates FOXO TFS. Richtig The APO-isoforms ε 2/8 2 and ε 2/ £3 are associated with reduced cardiovascular risk and improved health span. Richtig The APO-isoform ɛ 4/6 4 cause an increased risk of death below the age reached by less than 1% of a population. Richtig The FOXO Al variant increases the lifespan when combined with combined with social behavioural factors. Richtig All FOXO 3A variants were found more frequent in centenarians than in 90 years old humans. Richtig The answer on the question, whether a mutation or a nutritional condition can cause an effect along he msulin signaling pathway which is adverse or rather beneficial, strongly depends on how trang/drastic the mutation or the nutritional intervention is. Richtig Alpha-synuclein gathers in clumps called Lewy bodies being the major non-Aß component in AD. Richtig. → typical more in PD, but also possible in AD Knockout mutations in the ABPP are required and sufficient for the onset of AD. Richtig Enhanced expression (overexpression) of the ABPP can be responsible for the pathogenesis AD. Richtig Splice-site mutations in the ABPP gene can cause ectopic expression of ABPP-isoforms in the brain. Richtig Lack of cleavage mechanisms for ectopic ABPP-isoforms in the brain can cause accumulation of ABPP. Richtig Similar to the proteasomes, lysosomes enable cleavage of damaged proteins and toxins. Richtig Cleavage of proteins, lipids, and carbohydrates are catabolic processes induced by mTOR. Falsch→ not induced a-synuclein has its function in the release of dopamine. Richtig Loss of a-synuclein leads to DNA damage, formation of Lewy bodies, and cell death. Falsch→ not loss, bc to drastic Loss of ABPP leads to the formation of AB-plaques, TAU hyperphosph., and cell death. Falsch→ not loss, bc to drastic PINK1 is expressed in response to stress induced autophagy via FOXO3a. Richtig PPAR-Gamma is a transcriptional key regulator of genes involved in protein degradation. Flasch → hauptsächlich an der Regulation von Lipid- und Glukosemetabolismus Preinsulin proteins are involved in the proteolytic processing aóf alpha synuclein. Falsch → Alpha-Synuclein wird durch andere Proteasen (z. B. Calpain, Cathepsin D) abgebaut Supressorscreens are used for the identification of genes active in distinct pathways. Flasch→ random mutagenesis results in a more open effect Forward genetic screens are a powerful tool for the identification of novel genes. Richtig → including suppressor screens and simple screens. AD is defined by progressive loss of neurons caused by abnormal structure of the substantia nigra. Flasch → it´s PD, AD: Akkumulation von Beta-Amyloid-Plaques und Tau-Fibrillen The canonical mTOR signaling pathway reduces the normal life span increasing cell proliferation. Falsch→ mTor maintains the normal lifespan and does not shorten the lifespan Low intracellular and extracellular Glucose levels activate mTOR and inhibit AMPK. Flasch→ the other way around The pathogenesis of AD starts in the brain areas called hippocampus and cortex. Richtig FOXO TFs are transcriptional key regulators for genes involved in anabolic processes. Falsch → catabolic Loss-of-function mutations in the K+ channel KCNJ11 induce insulin storage in adipocytes. Falsch → KCNJ11 kodiert für einen Untereinheit des ATP-sensitiven Kaliumkanals (Kir6.2), der in Beta-Zellen des Pankreas eine zentrale Rolle bei der Insulinsekretion spielt. Loss-of- function-Mutationen in KCNJ11 führen zu Störungen der Insulinsekretion, wie bei Hyperinsulinämie oder Diabetes mellitus, aber nicht direkt zur Speicherung von Insulin in Adipozyten. The canonical mTOR signaling pathway shortens the normal life by stimulating of protein synthesis. Falsch → mTOR maintains the normal lifespan and does not shorten the lifespan PARKIN can be recruited by PINK1 to enable degradation of mitochondria (mitophagy). Richtig Low Intracellular and extracellular Glucose levels activate both, the AMPK and mTOR. Falsch → Low Glucose levels activate AMPK, but not mTor. Loss-of function mutations in the K+ channel KCNJ11 affect the release of insttlin in neurons. Falsch → K+ channel in pancreatic beta cells, not in neurons Acetylation, ubiquitinilation, methylation, and phosphorylation of proteins are indicators of protein misfolding. Falsch → Ubiquitinylation as marker for protein misfolding, but the other posttranslational modifications have nothing to do with misfolding. Presenilin proteins are involved in the proteolytic cleavage enabled by the y-secretase complex. Richtig Alternative splicing can generate different primary transcripts from one gene. Falsch → not different primary transcripts but mRNA transcripts Intracellular branched chain amino acids (BCAAs) activate the AMPK and inhibit mTOR. Falsch → the other way around Ubiquitinylation of proteins has the function to activate transcription. Falsch→ not really more activation by no ubi Alternative splicing processes can generate different mRNA transcripts from one primary transcript. Richtig Loss of mTOR activity mimics the effect of overnutrition. Falsch → Loss of mTor mimics effect of caloric restriction Loss of mTOR activity mimics the effect of FOXO inhibition. Falsch → FOXO is normally inhibited by normal working mTOR Forward-genetic approaches are based on random phosphorylations. Falsch → Random mutagenesis in forward genetic approaches, not phosphorylation. Phosphorylation can activate or inactivate specific proteins. Richtig An evolutionary conserved mTOR signaling pathway which is inactive promotes cell proliferation. Falsch → not inactive An alternative splicing process can generate different mRNAs from one protein. Falsch → not from a protein Ubiquitinylation of proteins indicates point mutations. Falsch → indicates protesomal degeneration Long term caloric restriction (CR) significantly reduces the cerebral amyloid expression and deposition in human hippocampal neurons. Richtig Forward genetic screens are powerful tools used for studying posttranslational modifications in proteins. Falsch → used for identification of mutation in specific phenotypes A gene can always encode for a single protein. Falsch → alternative splicing results in more than one mRNA Forward-genetic approaches are based on genome editing via CRISPR/Cas Falsch → not CRISPR (reverse) but random mutagenesis Genetic complementation implicates the expression of a wildtype gene in the corresponding mutant background. Richtig An evolutionary conserved mTOR signaling pathway which is inactive, promotes protein synthesis Falsch → inactive mTOR implicates catabolic processes Systemic IR- or IR5-knockout organisms can mimic the tissue-specific metabolism of T2DM. Falsch → systemic knockout cannot mimic tussue specific metabolism An alternative splicing process can generate identical mRNAs from one gene. Falsch → alternative splicing for different mRNAs from one prämRNA