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genetics concepts > Lecture 8 > Flashcards

Lecture 8 Flashcards

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Biology 101 flashcards
1
Q

why do we care about variations?

A
  1. underlie phenotypic differences
  2. caused inherited diseases
  3. allow tracking of ancestral human history
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2
Q

what does polymorphism mean?

A

a sequence variant that has an allele frequency of greater than 1% in the population

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3
Q

what are the types of variations in human genome?

A
  • single nucleotide polymorphism (SNP)
  • deletion/insertion polymorphisms (DIPs)
  • microsatellite or short tandem repeat (STR)
  • named variant
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4
Q

any 2 genomes are roughly how identical?

A

99.9%

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5
Q

how do we find sequence variations?

A
  • look at multiple sequences from the same genome region

- use base quality values to decide if mismatches are true polymorphisms or sequencing errors

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6
Q

what are the different types of snp’s?

A
  • coding snp’s
  • non coding snp
  • non coding silent snps
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7
Q

what are synonymous and non synonymous coding snps

A

synonymous: when single base substitutions do not cause a change in the resultant amino acid
- nonsynonymous: wehn single base substitutions cause a change in the resultant amino acid

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8
Q

what does synonymous coding snp changes create?

A

a new codon that still codes for the same amino acid

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9
Q

what does nonsynonymous coding snp changes create?

A

a new codon that codes for a new amino acid

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10
Q

what is the difference between snp and mutation?

A

an snp is a polymorphic position where the point mutation has persisted in the population. snps have greater than a certain minor allele frequency

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11
Q

what is the life cycle of snp?

A
  1. appearance of new variant by mutation
  2. survival of rare allele due to bottleneck effect
  3. increase in allele frequency after population expand
  4. new allele if fixed in the population as novel polymorphism
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12
Q

what are the two types of the influence of genotype on disease phenotype?

A
  1. disease risk-disease prone and disease proof genotypes

2. treatment response- balancing benefits and side effects of drug

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13
Q

what is significant about ApoE4 polymorphism as it pertains to diseases?

A
  • apoE plays a central role in lipid metabolism
  • occurs in 4 forms apoE2, E3, and E4
  • apoE4 is a major risk factor for alzheimers and increased risk for heart disease
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14
Q

for familial Alzheimers, what genes are involved?

A

all known autosomal dominant genes relate to beta amyloid (app) processing

  • presenilin 1 and 2
  • app
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15
Q

what genes are involved in non-familial alzheimers?

A
  • apoe that is expressed in the brain
  • at least 20 other genes suspected of relating to AD
  • apoE4 favor myelination, beta amyloid deposition
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16
Q

what are the some of the age factors for apeE4 allele frequency?

A

decreases with age and is lowest in centenarians

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17
Q

what is bad about apoE2?

A
  • protective for alzheimer, but 95% of type 3 hyperlipoproteinemia are homozygous for apoE2
  • high cholesterol and triglycerides serum levels are due to low affinity of apoE2 to its receptor and leads to coronary and vascular peripheral disase risk
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18
Q

what has apoE4 found to protect people against?

A

cognitive development in children with heavy diarrhea burdens in northeast brazil

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19
Q

what are some of the demographic stats with apoE?

A
  • 1/4 of americans have at least one copy of apoE4
  • 1/2 of all african americans with apoe4
  • white have greater risk for alzheimers than african americans
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20
Q

what is p53 big in?

A
  • cancer prevention gene

- mutations in p53 lead to cancer

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21
Q

what is the relationship of arginine and proline to p53?

A
  • arg stimulates apoptosis more
  • pro stimulates apoptosis less, but arrests proliferation better
  • tp53 pro/pro has more cancer risk compared to arg/arg carriers
  • pro/pro genotype have a 41% increased survival despite increased mortality to cancer
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22
Q

p53 protects against cancer but at the cost of what?

A

longevity

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23
Q

patients with pro/pro genotype have an increased what?

A

survival after the development of cancer or even after the development of other life threatening diseases

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24
Q

what is the question for Pharmaco/ToxicoKinetics?

A

how the chemical is eliminated from the body or activated into a toxic species (ADME)

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25
Q

what is the question for Pharmaco/ToxicoDynamics?

A

how the chemical exerts its pharmacological effect/toxicity target receptor/cell/organ

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26
Q

how are fast and slow acetylators distinguished?

A

by measuring plasma concentrations 6 hours after administration of an identical oral dose

27
Q

what is methotrexate (MTX)?

A

-a key drug in acute lymphocytic leukemia and also is widely used for other cancers

28
Q

what does mtx inhibit?

A

its an antifolate drug that inhibits transmethylation reactions

29
Q

what are the symptoms associated with toxicity after chronic treatment with low doses of mtx in patients undergoing bone marrow transplantation

A
  • hepatotoxicity
  • pulmonary problems
  • enteritis/colitis
  • nausea
30
Q

what does tamoxifen do?

A

blocks estrogen from receptors in breast while it mimics estrogen in other tissues

31
Q

what diseases does tamoxifen help with?

A

protects against breast cancer, osteoporosis and heart attack

32
Q

what are the non-SNP polymorphisms influencing disease phenotypes?

A
  1. insertion/deletion (INDEL) polymorphisms

2. copy number variants

33
Q

what are examples of indel polymorphisms?

A
  • angiotensin converting enzyme (ACE)

- CCR5 (HIV infection)

34
Q

what is the predispostion to creations of indels?

A

sequence repetitiveness in the form of direct or inverted tandem repeats

35
Q

what is ACE/ID?

A

an indel responsible for 50% of the inter individual variability of plasma ACE concentration

36
Q

ace indel polymorphism influences the development of what?

A

retinopathy in diabetics

37
Q

what kind of receptors does HIV-1 env mediated fusion and virus infection require?

A

CXCR4 and CCR5

38
Q

what does the CCR5 receptor bind and what is CCR5 expressed on?

A 
binds:
-MIP-1a
-MIP-1b
-rantes
expressed on:
-macrophages, monocytes, memory T cells, dendritic cells, and microglial cells
39
Q

what is the relationship of DEL32 to HIV progression?

A

heterozygotes del32 have delayed progression of AIDS and homozygotes resist HIV infection

40
Q

what does a 32 bp deletion result in concerning the CCR5 receptor?

A

a premature truncation of the protein, has no functional activity, mutant protein is unstable in the cytoplasm

41
Q

are people with del32 healthy?

A

yes

  1. individuals homozygous for the mutant allele are healthy and have no apparent immunological conditions
  2. genotypic frequences do not differ significantly from those predicted by Hardy-Weinburg equilibrium, suggesting no effect on fitness
42
Q

what is CCR5 piece of history in europe?

A

began to spread in northern europe during past 700 years when population was ravaged by a plague. May have helped people with resistance

43
Q

what are some genetic factors predisposing to AIDS?

A

HLA genes that influence responsiveness, full heterozygosity for class 1 HLA results in delayed progression. Allows the host to respond to a greater diversity of viral antigenic epitopes

44
Q

what is CCL3L1?

A

CC-chemokine ligand 3 like protein, a ligand for CCR5

45
Q

what is a low CCL3L1 copy number associated with?

A

an increased susceptibility to AIDS progression.

46
Q

how can CCL3L1 be altered and what would the purpose be?

A

could dupli/multiplicate in genome, more copies means better protection because ligand is competing with virus for CCR5 binding

47
Q

CCL3L1 copy number is strong genetic determinant of what?

A

of HIV seropositivity in caucasian intravenous drug users, so high copy number are less likely to contract HIV

48
Q

t or f: africans having more CCL3L1 copies on average do not help them

A

true

49
Q

the CCL3L1-CCR5 del genotype strongly predicts what?

A

SLE:systemic lupus

50
Q

how could copy number variations be detected?

A
  1. aCGH (array comparative genome hybridization)
  2. NextGen sequencing
  3. SNP arrays (homozygous stretches)
51
Q

for 16p11.2 CNVs, only deletion does what? both deletion and duplication leads to what?

A

just deletion predisposes to autism, both deletions and duplications cause a variety of problem

52
Q

many of the features in 16p11.2 carriers occur on a spectrum that can be described as what?

A

indistinguishable for the variation in the general population

53
Q

know the conclusions from slides 84 about graph 83

A

slides 84 and 83

54
Q

many polymorphisms dont cause diseases itself but may serve as what?

A

disease markers

55
Q

non disease causing polymorphisms mapped to the genome may serve as what?

A

markers to identify other genes that do cause disease when mutated

56
Q

variations when co-inherited with a particular trait provide evidence for what?

A

where the traits gene is located in the genome

57
Q

what is allelic association?

A

non-random assortment between alleles. measures how well knowledge of the allele state at one site permits prediction at another

58
Q

significant allelic association between a marker and a functional site permits what?

A

localization (mapping) even without having the functional site in our collection

59
Q

the strength of allelic association is measured how?

A

between 2 or more markers, there are pair wise and multi-locus measures of association

60
Q

a marker locus is associated with what?

A

a disease if the distribution of genotypes at the marker locus in disease affected individuals differs from the distribution in the general population

61
Q

what are the ways a specific allele may be associated?

A

positively or negatively

62
Q

the most useful multi marker measures of associations are related to what?

A

haplotype diversity

63
Q

what is strong association?

A

most chromosomes carry one of a few common haplotypes-reduced haplotype diversity in diseased individuals

64
Q

what is the haplotype promise for medical genetics?

A

within blocks a small number of SNPs are sufficient to distinguish the few common haplotypes this possibly leads to significant reduction in a number of markers

genetics concepts (13 decks)

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