theory of prac 10% Flashcards

1
Q

what are the Nutrigenomics research strategies

A
  • Promise a healthy world and control your health
  • Ultimate goal is that the food can be match to the individual’s genotype
  • Need a lot of research
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2
Q

what is the nitrogenomics research strategies research cycle

A
  1. hypothesis and research question is carried out
  2. experiment
  3. test hypothesis
    a. accept hypothesis-> part of the theory can be formulated
    b reject hypothesis-> fomulate hypothesis and research question again
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3
Q

Mechanism-based approach

A
  • Address the relation between nutrition. Health. Disease, Genome and the genes
  • Important to develop sound research question
  • Can be done by look specific food (e.g. fruit) or specific nutrients (e.g. calcium)
  • By focus on effect on diet or specific organ (e.g. liver, colon) or disease (e.g. T2D or risk of develop these disease
  • The influence of genes can be more specific investigate look at 1 or few genes or at specific metabolic pathway e.g. gluconeogenesis
  • However it is also possible the study of diet at transcriptome, proteome and metabolome level, this means look at as many as biological parameters as possible.
  • More focused Research question is what is the role of n-3 fatty acids on PPAR alpha in liver?
  • Once the research question is formulated, the research start. At the end this will lead to between understanding of nutrition and disease
  • This approach is mechanism based approach
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4
Q

Holistic approach

A
  • Use the same genomic approach as mechanism base approach.
  • However it does not primary focus on understanding specific mechanism, rather it focused on complex relation between nutrition, genomics, health and disease.
  • Some genes are expressed and some not, the specific expression can be measured by oligonucleotide microarray
  • They compare expression profile e.g. compare between people eat fish, and some don’t. this can be show what the effect of fatty acid and other component in fish on gene expression but for most genes detected in this experiment, exact function is not known.
  • This approach unlikely to solve the mechanism by fatty acid in fish influence health
  • This approach provide us with genomic signatures
  • Genomic signature describe the expression profile associate with specific nutrients or diet or disease, also proteomics and metabolomics can be used to develop the genomic signatures.
  • Can consider the genomic signature as fingerprint of physiological or pathophysiological state or finger print of phenotype
  • In the future, develop database for characteristic signatures. With this database, perhaps it will be possible to predict whether someone with a particular signature will be benefits with certain supplement. Moreover, these signature might indicate whether the person is at risk of getting some diseases. The signature could serve as an early biomarker for disease
  • Holistic based approach may also give on rise on hypothesis on a particular hypothesis, they use mechanism base approach.
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5
Q

Are the personalized diets indeed PERSONAL diets?

A

The following issues must be mentioned in your conclusion:

  • Less than 0.07% of all genes are screened for variations. There are many more (unknown) variations which could be important for a personalized diet advice.
  • The “personal diet advice” is not very personal. Is is nearly the same as the general guidelines of “The American Hearth Association” (especially for macronutrients).
  • Some of the general guidelines (regarding micronutrients) are stressed more than others, based on certain variations. This is a “personal” part of the advice.
  • Most guidelines given in the personalized diet advice is not only of relevance for the specific individuals with certain variations but also for individuals without these variations.

Note that some companies also base their advice on results of lifestyle and food questionnaires the customer filled in. This advice is of course personal, but not based on the genome. Some times such advice is called “personalized diet advice”. However, most of the time this advice is called “tailored advice”. In this course “personalized diet advice” is defined as diet advice based on genetic tests.

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6
Q

How many genes, do you think, are approximately in the human genome?

A

it is not exactly known of how many genes the human genome consists, but their number is estimated around 25.000.

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7
Q

Which of the techniques below is most probably used by the companies that give a personalized diet advice?

A

a multiplex technique: several SNPs can be detected simultaneously.this one is most likely used by the companies. With this technique a small number of SNPs can be screened at once. It can be largely automated, therefore the costs are low. However, there are other techniques, like these, to analyze many SNPs simultaneously, which also could be used by the companies.

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8
Q

what r the micronutrients

A
folate
calcium
Vitamin B6
vitamin D
vitamin B12
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9
Q

what r the macronutrients

A

saturated fats
carbohydrates
cholesterol
n-3 fatty acids

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10
Q

what does antioxidants, caffeine, fruit and vege belong

A

they dont belong to micro or macro nutrients

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11
Q

Compare the diet advice in the report with the general dietary guidelines of the American Hearth Association and the general dietary guidelines for Americans. What is your conclusion about macro and micro nutrients

A

For macronutrients the advice given in the report is almost the same as the general guidelines of the American Heart Association. In general, this is also the case for micronutrients. However, some advice regarding micronutrients is stressed more than others depending on variations in some genes or a persons food pattern. Correct your answer if necessary.

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12
Q

Are the personalized diets indeed PERSONAL diets?

A

The following issues must be mentioned in your conclusion:

  • Less than 0.07% of all genes are screened for variations. There are many more (unknown) variations which could be important for a personalized diet advice.
  • The “personal diet advice” is not very personal. Is is nearly the same as the general guidelines of “The American Hearth Association” (especially for macronutrients).
  • Some of the general guidelines (regarding micronutrients) are stressed more than others, based on certain variations. This is a “personal” part of the advice.
  • Most guidelines given in the personalized diet advice is not only of relevance for the specific individuals with certain variations but also for individuals without these variations.

Note that some companies also base their advice on results of lifestyle and food questionnaires the customer filled in. This advice is of course personal, but not based on the genome. Some times such advice is called “personalized diet advice”. However, most of the time this advice is called “tailored advice”. In this course “personalized diet advice” is defined as diet advice based on genetic tests.

-

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13
Q

which of the human chromosomes contain MTHFR

A

chromosome 1

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14
Q

what does MTHFR do

A

the MTHFR gene encodes for the enzyme methylenetetrahydrofolate reductase, which is involved in the metabolism of folate.

5-methyltetrahydrofolate serves as a methyl donor to remethylate homocysteine to methionine. this process requires vitamin B12. elevated levels of homocysteine are associate with a high risk of heart diseases.

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15
Q

what is the gene product of the PPAR gamma gene

A

“The peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor subfamily of transcription factors.”

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16
Q

what is the association of PPAR gamma with adipose tissue

A

PPAR gamma activation is association with higher fatty acid and glucose uptake

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17
Q

what is the association of PPAR gamma with muscle

A

PPAR gamma activation is association with higher glucose usage in muscle

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18
Q

what is the association of PPAR gamma with liver

A

PPAR gamma activation is association with higher fatty acid storage in the liver and lower glucose production in the liver

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19
Q

what is the association of PPAR gamma with pancreas

A

PPAR gamma activation is association with higher activity of beta cells in the pancreas. the beta cell secrete insulin

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20
Q

give an important polymorphism in the PPAR gamma gene

A

an important polymorphism in the PPAR gamma gene is “Pro12Ala)

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21
Q

Pro12Ala polymorphism

A

the Pro12Ala polymorphism is associated with a REDUCED trranscription of the PPAR gamma gene
There is evidence that this polymorphism is also associated with a LOWER BMI, a LOWER fasting glucose level, a HIGER level of HDL cholesterol and a INCREASED insulin sensitivity.
Therefore the Pro12Ala polymorphism may DECREASE the risk of insulin resistance, DECREASE the risk of T2D and DECREASE the risk of heart disease. so the polymorphisms in PPAR gamma gene can have a lot of effects.

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22
Q

whar r GSTM and GSTT

A

GSTM1 and GSTT1 are classes of enzymes called GSTs (gluthatione-S-transferase). there are polymorephisms in the GSTT1 and GSTM1 genes (deletion of the part of the gene) that cause a reduction of the enzyme activity. these polymorphisms (deletions) are associated with diseases like cancer and autoimmune diseases.

23
Q

what is VDR

A

the gene VDR encodes the vitamin D receptor. this is a transcription factor.
SNPs in the VDR gene are associated with a higher risk of osteoporosis

24
Q

describe the mechanism of VDR

A
  1. in the cytoplasm (derivates of ) vitamin D binds to the vitamin D receptor
  2. the vitamin D receptor - vitamin D complex moves to the nucelus
  3. in the nucleus an other receptor *the retinoic X receptor) binds to this complex
  4. the whole complex binds to speciific binding sites of the DNA
  5. there it influences transcription of genes which are involved in processes which has something to do with bone health
25
Q

what is IL-6

A

interleukins are members of the family of cytokines. cytokines are small protein that play a role during inflammation. ILs are produced and secreted by leukocytes (WBC). some interleukin have pro-inflammatory effect other anti-inflammatory.
- ILs influence the processes in cells by binding to the cell membrane. different rx can occur as an effect of the release of Il-6.

26
Q

give an e.g. of IL-6 polymorphism

A
  • the G174C polymorphism in the gene, which encode IL-6 is associate with a higher BP and an increased risk of myocardial infaction.
  • the G634C polymorphism is associate with a lower bone density and a higher risk of osteoporosis.
27
Q

what is the gene APOC3

A

the gene APOC3 encodes for the apolipoprotein C-III

28
Q

what does lipoprotein contain

A
  1. phospholipids
  2. Apolipoproteins (like ApoCIII) are part of lipoproteins which transport lipids in the plasma and play a role in lipid metabolism
  3. cholesterol
  4. cholesterol
  5. triacylglycerol
  6. cholesteryl ester
29
Q

what is the SNPs in the ApoCIII gene

A

SNPs in the ApoCIII gene are asscoaite with higher levels of triacylglycerols in the plasma. this can lead to arteriosclerosis and coronary heart disease.

30
Q

what is the function of cholesterol and tricylglycerol do in body

A

cholesterol and tricylglycerol have several important functions within the body. they are insoluble particles and must be packaged into lipoproteins to circulate in the plasma, from sites of synthesis or absorption to sites of use.

31
Q

what is general relation between genotype and the phenotype

A

in general the phenotype is determined by the genotype and external factors (e.g. lifestyle and nutrition )
therefore it is possible that a certain genotype e (e.g. a polymorphism) leads in different people, to different phenotypes

32
Q

what is the relationship between MTHFR and phenotyoe

A

polymorphism in MTHFR gene —folate intake–> phenotype: homocysteine concentration.

  • sometimes there is a clear relation between the genotype, the phenotype and the effect of certain nutrients.
    e. g. the TT polymorphism in the MTHFR gene leads to a high homocysteine conc. only when folate intake is low
33
Q

what is the relationship between polygenetic and phenotype

A

APOC3 gene, PPARg gene, IL-6 gene, MTHFR gene—physical activity, fatty acid intake, smoking alcohol—> phenotype: coronary heart disease

  • most of the time, the relation between genotype, external factors and the phenotype is complex. e.g. the phenotype coronary heart disease is determined by the interaction of several genes (and polymorphisms in these genes ) and external factors.
  • therefore diseases like coronary heart disease are called ‘polygenetic complex diseases” because these diseases are controlled by several genes at onece, in interaction with several external factors.
34
Q

list the genes tested for are example of SNPs

A

MTHFR, PPAR gamma, VDR, IL-6, APOC3 are SNP

35
Q

what is GSTM1 and GSTT1 genes

A

deletions of a part of the gene

36
Q

is it always bad with a SNP in one of the tested genes discovered

A

Some variations are beneficial, others are not. E.g. having the Pro12ala polymorphism in the PPARgamma gene is beneficial: it is associated with a lower risk of diseases like diabetes II and heart diseases. Other polymorphisms (e.g. in the GSTM1 gene) are associated with a higher risk of certain diseases.

37
Q

what r the e.g. of polygenetic disease

A

an inherited disease controlled by several genes at once.
- T2D, obesity, high BP, high cholesterol, CVD, cancer, osteoporosis
Sometimes a disease could be polygenetic and monogenetic. For example there are single gene orders which causes obesity or high cholesterol levels, however the most common forms of these diseases are polygenetic. Examples of true monogenetic diseases are cystic fibrosis and Huntington disease.

38
Q

what r the genes related to the heart health

A

PPAR
APOC3
MTHFR
IL-6

39
Q

what r the genes related to the detoxification

A

GSTT1

GSTM1

40
Q

what r the genes related to the antioxidant activity

A

GSTT1

GSTM1

41
Q

what r the genes related to the vitamin B use

A

MTHFR

42
Q

what r the genes related to the bone health

A

VDR

IL-6

43
Q

what r the genes related to the inflammation

A

IL-6

44
Q

what r the genes related to the insulin sensitivity

A

PPAR

45
Q

what variation in genes such that the given advise is increase intake of fruit and vegetables

A

variation which influence heart health or antioxidant activity (APOC3, MTHFR, IL-6, GSTT1, GSTM1)

46
Q

what variation in genes such that the given advise is eat food rich in calcium and vitamin D

A

variation in the VDR gene

47
Q

what variation in genes such that the given advise is limit cholesterol intake

A

all variation which increase risk of heart diseases (APOC3, MTHFR,IL-6, GSTT1, GSTM1)

48
Q

what variation in genes such that the given advise is eat foods rich in vitamin B12

A

variation in the MTHFR gene

49
Q

what variation in genes such that the given advise is increase intake of folate

A

variation in MTHFR gene

50
Q

do you think that screening for variation in the 19 genes which r tested at this moment is sufficient to give a personalized diet advise?

A

In your answer the following issues must be mentioned.

  • The genes tested for SNPs may be involved in a complex metabolic pathway. The diet advice does not take these complete metabolic pathways into account.
  • Diseases like coronary heart disease etc. are polygenetic complex diseases. Not all genetic factors which influences these diseases are known.
  • Although some SNPs give rise to a specific nutritional advice (e.g. use more folate), foods are complex and are not purified components. For example, foods containing folate contain also many other components of which the health effect is not known. Also not everything about the interaction between the different components in food is known.
  • So there is a lot more to know about nutrition, genes and metabolic diseases.
51
Q

what involved in mechanism based research

A

mechanism

understanding

52
Q

what involved in holistic research

A

holistic
prediction
genomic signature

53
Q

what involve in both mechanism and holistic based research

A

personalized diet, nutrition, proteomics, metabolomics, transcriptomics, genomics

54
Q

Give your opinion about the role of nutrigenomic research in the development of personalized diets.

A

The following issues must be mentioned in your conclusion:

  • Nutrigenomics research aims at understanding the relation between nutrition, health and disease. Before it is possible to give a detailed personalized diet advice based on a persons DNA much research is necessary.
  • Nutrigenomics research based on the holistic approach generates many data. At this moment it is difficult to draw conclusion from these data. First, tools must be (further) developed to explore and catalogue these data (bioinformatics). This will requires several decades. After that maybe a more personalized diet advice can be given.