Final - Genetics Flashcards

(121 cards)

1
Q

Quantitative genetics

A

the study of traits that can be described numerically

Any trait that varies measurably in a given species

Such traits that are usually controlled by more than one gene (complex traits)

Ex: height, metabolism rate, milk production, litter size

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2
Q

Why is quantitative genetics important?

A

Most of the key characteristics considered by plant and animal breeders are quantitative traits

Many human diseases are influenced by several genes

Many of the traits that allow a species to adapt to its environment are quantitative traits

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3
Q

In many cases, quantitative traits are easily ______ and described ______

A

measured; numerically

Ex: weight in kg, speed in km/hr, metabolic rate in grams of glucose burned per minute

The measurement of quantitative traits is essential when comparing individuals or evaluating groups of individuals

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4
Q

Discontinuous traits

A

Traits that fall into discrete categories

The alleles that govern these traits affect the phenotype in a qualitative way (ie: white or red eyes, short or long fur)

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5
Q

Frequency distribution

A

An alternative way to describe quantitative traits, as they do not naturally fall into a small number of discrete categories

To construct a frequency distribution, the trait is divided arbitrarily into a number of discrete phenotypic categories

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6
Q

Variance (Vx)

A

A common way to evaluate variation within a population

Vx = sum of (value - mean)^2/(degrees of freedom - 1)

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7
Q

Variances are very important in the analysis of quantitative traits because they are ______ under certain conditions

A

additive

The variances of factors that contribute to a quantitative trait can be added to predict the total variance for that trait

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8
Q

Standard variation (SD)

A

The square root of variance

Allows us to gain an intuitive grasp of variation

If the values in a population follow a normal distribution, then it is easier to appreciate the amount of variation by considering the standard deviation

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9
Q

Covariance (CoV(x,y))

A

Describes the degree of variation between two variables within a group

CoV(x,y) = sum[ (X - mean of X variables) (Y - mean of Y variables)]/(total pairs of observations -1)

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10
Q

Correlation coefficient (r)

A

Used to evaluate the strength of association between two variables

r(x,y) = CoV(x,y) / (standard deviation of X)(standard deviation of Y)

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11
Q

What do r>0, r=0, and r<0 mean (correlation coefficient)?

A

r value ranges between +1 and -1 and indicates how two factors can vary in relation to each other

If r > 0 –> as one factor increases, the other factor will increase with it

If r = 0 –> the two factors are not related

If r < 0 –> as one factor increases, the other factor will decrease

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12
Q

Like the Chi square value, the significance of the correlation coefficient is directly related to:

A

Sample size

Degrees of freedom

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13
Q

What hypothesis is used to test the correlation coefficient?

A

There is no real correlation (the null hypothesis)

The r value differs from 0 only as a matter of chance

This hypothesis being rejected means there is a real correlation between the two values

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14
Q

Hypothesis testing for the correlation coefficient is only valid if two assumptions are met:

A
  1. The values of X and Y are obtained by an unbiased sampling of the entire population
  2. The scores of X and Y follow a normal distribution and that the relationship between X and Y is linear
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15
Q

An r value that is statistically significant need not imply ____________

A

a cause-and-effect relationship

The positive association between factors may not be due to genetics

Rather, it may be rooted in environmental factors

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16
Q

Regression analysis

A

Predicts how much one variable will change in response to the other

Valid to use when it has been established that the variables are related due to cause and effect

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17
Q

Most quantitative traits are ________ and exhibit a continuum of ___________

A

polygenic; phenotypic variation

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18
Q

Polygenic inheritance

A

refers to the transmission of traits that are governed by two or more genes

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19
Q

Quantitative trait loci (QTLs)

A

The locations on chromosomes that affect the outcome of quantitative traits

QTLs are genomic regions (identified by molecular markers) that are often associated with a particular phenotype

QTLs may contain one or more genes, some or all of which may affect quantitative traits

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20
Q

Nilsson-Ehle Cross

A

P: True-breeding red X true-breeding white
F1: Intermediate red
F2: Great variation in redness (white, light red, intermediate red, medium red, dark red)

Nilsson-Ehle discovered that the colors fell into a 1:4:6:4:1 ratio

He concluded that this species is diploid for two different genes that control hull color

Each gene exists in two alleles: red or white

He hypothesized that these two loci must contribute additively to the color of the hull

The contribution of each red allele to the color of the hull is additive

Later, it was discovered that a third gene affects hull color

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21
Q

Many polygenic traits are __________ to categorize into several discrete genotypic categories

A

difficult or impossible

This is especially true when:
1. The number of genes controlling the trait increases
2. The influence of the environment increases

Therefore, a Punnett square cannot be used to analyze most quantitative traits, instead, statistical methods must be employed

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22
Q

What is the issue with trying to identify the genetic underpinnings of a disease with polygenic traits?

A

There are many genes that contribute these traits

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23
Q

Geneticists use ____________ to
determine the regions of the chromosome that are
associated with a particular trait

A

molecular marker analysis

After analysis of many genomes they might make associations with particular molecular markers and particular phenotypic outcomes= Quantitative Trait Loci (QTL)

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24
Q

Because many mutations are known in Drosophila, they can serve as _________

A

genetic markers

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25
What is the general strategy for identifying QTLs?
Cross two strains that differ in genetic markers and in the quantitative trait of interest Backcross the F1 offspring to the parental strains This produces a population of F2 offspring that differ with regard to their combinations of parental chromosomes Most individuals will contain a few chromosomes from one parental strain and the rest from the other strain The genetic markers on the chromosome provide a way to determine which chromosome came from which parent
26
What was the DDT resistance in Drosophila experiment?
In 1957, James Crow conducted one of the earliest studies to show linkage between genes affecting quantitative traits to genes affecting discontinuous traits Crow, who was interested in evolution, spent time studying insecticide resistance in Drosophila He noted: “Insecticide resistance is an example of evolutionary change, the insecticide acting as a powerful selective sieve for concentrating resistant mutants that were present in low frequencies in the population.” Crow’s aim was to determine the genetic basis for insecticide resistance in Drosophila melanogaster The hypothesis: DDT resistance is a polygenic trait
27
What was the result of Crow's DDT resistance in Drosophila experiment?
The data shows that each copy of the chromosomes 1 (X), 2, and 3 confers some insecticide resistance Maximal resistance is obtained when chromosomes from only the insecticide-resistance parental strain are present DDT resistance was less than maximal, even when only a single chromosome was derived from the sensitive strain These results are consistent with the hypothesis Resistance to DDT is a polygenic trait involving multiple genes on chromosomes 1 (X), 2 and 3
28
Genetic markers in genomic maps make it easier to:
determine the number of loci that affect a quantitative trait
29
Detailed genomic maps have been obtained from:
Model organisms Organisms of agricultural importance
30
QTL mapping
QTLs are now mapped by linkage to molecular markers Researchers map eukaryotic genes by identifying molecular markers that are close to such genes Eric Lander and David Botstein extended this to identify QTLs that govern a quantitative trait The basis of QTL mapping is the association between genetically derived phenotypes (e.g., quantitative traits) and molecular markers
31
For QTL mapping, the strains mapped must be different in two important ways:
1. With regard to a quantitative trait of interest (e.g., Large vs. small fruit) 2. With regard to many molecular markers (e.g., 1A vs 1B) The markers should correspond to the same chromosomal location and should be distinguishable at the molecular level
32
All traits of biological organisms are influenced by _______ and _________
genetics and the environment This is particularly true with quantitative traits A geneticist, however, can never actually determine the relative amount of a quantitative trait that is controlled by genetics and the environment Instead, the focus is on how variation, both genetic and environmental, will affect the phenotypic results
33
Heritability
the amount of phenotypic variation within a group of individuals that is due to genetic variation In most cases, the heritability value lies between 0 and 1
34
What does a heritability value of 1 mean?
All the phenotypic variation in a group was due to genetic variation
35
What does a heritability value of 0 mean?
All the phenotypic variation was due to environmental factors
36
When studying phenotypic variance, we have to assume the following:
1. Genetic and environmental factors are the only two components that determine a trait (can't measure the environmental variance) 2. These factors are independent of one another
37
Population
a group of individuals that are able to interbreed Populations typically are dynamic units that change from one generation to the next A population may change in size, geographic location, and genetic composition
38
What is the equation used to calculate total variance (VT)
VT = VG + VE VT is the total variance (amount of variation at a phenotypic level) VG is the relative amount of variance due to genetic variation VE is the relative amount of variance due to environmental factors
39
If VG is very high and VE is very low:
Genetics is more important in promoting variation
40
If VG is very low and VE is very high:
The environment causes much of the phenotypic variation
41
VG and VE can be determined by comparing the variation in traits between _________ and _________
genetically-identical and genetically-disparate groups For example, geneticists have developed genetically homogeneous strains of mice through inbreeding These mice are monomorphic for all or nearly all genes In such an inbred strain of mice, VG = 0, therefore, all phenotypic variation is due to VE The variance of a homogeneous population (VG = 0) with regard to weight, for example, can be compared to the variance of a heterogeneous population (VG = ?) The two populations could be raised under the same environmental conditions (VE = constant) and the weights measured
42
Monomorphic
All members of a population are homozygous for the same allele of a given gene A monomorphic gene exists predominantly as a single allele By convention, when a single allele is found in at least 99% of all cases, the gene is considered monomorphic
43
In many cases of phenotypic variation, _______ and ________ interact
genetics and environment Interactions between genetics and environment are common
44
Genotype-environment association
When certain genotypes are preferentially found in a particular environment Genotypes may not be randomly distributed in all possible environments Very common in human genetics: Large families will tend to have a similar environment compared to the population as a whole Attempt to correct by looking at identical vs. fraternal twins Can also correct by looking at siblings adopted by different families
45
Broad sense heritability (hB2)
Accounts for all genetic variation that may affect the phenotype Heritability is the proportion of the phenotypic variance that is attributable to genetic variation hB2 = Vg/VT hB2 is the heritability in the broad sense VG is the variance due to genetics VT is the total phenotypic variance (VG + VE)
46
VG equation
Geneticists usually subdivide VG into three different genetic categories VG =VA +VD+VI VA is the variance due to the additive effects of alleles VD is the variance due to alleles that follow a dominant/recessive pattern of inheritance VI is the variance due to the effects of alleles that interact in an epistatic manner In analyzing quantitative traits, geneticists often focus on VA and neglect the contribution of VD and VI
47
Narrow sense heritability
The heritability of a trait due to the additive effects of alleles hN2 = VA/VT
48
What is the common strategy for calculating narrow sense heritability?
1. Measure a quantitative trait among groups of genetically related individuals 2. Use this data to compute a correlation between the individuals 3. Calculate narrow sense heritability as hN2 = r(obs)/r(exp) r(obs) is the observed phenotypic correlation between related individuals r(exp) is the expected correlation based on the known genetic relationship Note: For siblings, r(exp) = 0.5 For identical twins, r(exp) = 1.0 For parent-offspring relationship, r(exp) = 0.5 For uncle-niece relationship, r(exp) = 0.25
49
Heritability of dermal ridge count in human fingerprints
Fingerprints are inherited as a quantitative trait Francis Galton was the first to study fingerprint patterns However, Kristine Bonnevie made the trait more amenable to genetic studies She developed a method for counting the number of ridges within a human fingerprint Human fingerprints can be categorized as having an arch, loop, or whorl. The primary difference among these is the presence of the number of triple junctions, each known as a triradius Bonnevie conducted a study on a small population where she found that ridge count correlations were relatively high in genetically related individuals Sarah Holt carried out a more exhaustive study of ridge counts in a British population In groups of 825 males or 825 females, the ridge count on all 10 fingers varied from 0 to 300 Hypothesis: Dermal ridge count has a genetic component, this experiment aims to determine the contribution of genetics in the variation of dermal ridge counts
50
What does heritability describe?
the amount of phenotypic variation due to genetic variation for a particular population raised in a particular environment The terms variation, particular population, and particular environment cannot be overemphasized For example, the heritability for milk production may be 0.35 in one cattle population and 0.1 in another In addition, a heritability value of 1.0 only means that the amount of variation within this group is due to genetics. The environment may be quite important, it is just not causing much variation within this group
51
What does a 0.6 heritability value mean for IQ testing?
It means that 60% of the variation in IQ testing ability is due to genetic factors in a particular population in a particular environment It does not mean that 60% of an individual’s IQ testing ability is due to genetics and 40% is due to the environment It cannot be overemphasized that heritability is meaningless at the level of a single individual Heritability is a populational value that pertains to variation
52
Selective breeding
the modification of phenotypes in plant and animal species of economic importance It is also called artificial selection
53
The primary difference between artificial and natural selection is:
how the parents are chosen Natural selection is due to natural variation in reproductive success In artificial selection, the breeder chooses individuals with traits that are desirable from a human perspective
54
The phenomenon that underlies selective breeding is _______
variation Within a group of individuals, there may be allelic variation that affects the outcomes of quantitative traits The breeder chooses parents with desirable phenotypic characteristics These will pass on the advantageous alleles to their offspring Indeed, the selective breeder will often choose genetically related individuals as the parental stock (inbreeding)
55
Quantitative traits are often at an _______ value in unselected populations
intermediate Therefore, artificial selection can increase or decrease the magnitude of the trait Nevertheless, there is a limit
56
Selection limit
After many generations of selective breeding, the population will eventually become monomorphic for all or most of the desirable alleles in question At this point, additional selective breeding will have no effect At the start of the experiment the heritability for the trait is fairly high At the end, it is near zero
57
Realized heritability
Response to selection The most common way to estimate narrow sense heritability in a starting population hN2 = R/S where R is the response in the offspring to selection and S is the selection differential in the parents R = (mean of the offspring) - (mean of the starting population) S = (mean of the parents) - (mean of the starting population)
58
The central issue in population genetics is ________________
genetic variation Its extent within populations, why it exists, how it changes over the course of many generations
59
Population genetics is a direct extension of:
Mendel’s laws of inheritance, molecular genetics, and the ideas of Darwin Like quantitative genetics, the focus is shifted away from the individual and toward the population of which the individual is a member
60
Conceptually, all alleles of every gene in a population make up the ________________
gene pool Only individuals that reproduce contribute to the gene pool of the next generation Population geneticists study the genetic variation within the gene pool and how it changes from one generation to the next
61
Subpopulations
usually components of a large population Also called local populations or demes Members of a subpopulation are far likelier to breed with each other than with members of the general population Subpopulations are often separated from each other by moderate geographic barriers
62
Polymorphism
refers to the observation that many traits display variation within a population At the DNA level, polymorphism is due to two or more alleles that influence the phenotype In other words, it is due to genetic variation Polymorphic is also used to describe a gene that commonly exists as 2 or more alleles in a population
63
Variation can be even a _______________
single-nucleotide polymorphism (SNP) These account for 90% of variation between people In humans, a gene that is 2000-3,000 bp contains 10 different polymorphic sites on average
64
Allele frequency calculation
Allele frequency = (number of copies of an allele in a population)/(total number of all alleles for that gene in a population)
65
Genotype frequency calculation
Genotype frequency = (number of individuals with a particular genotype in a population)/(total number of all individuals in a population)
66
How do you figure out the frequency of one allele (i.e. G) just by knowing the frequency of the other allele (i.e. g)?
The sum of the frequencies of both alleles should be 1 If you know g, then G = 1 - g For monomorphic genes, the allele frequency for the single allele will be equal to or close to 1
67
The Hardy-Weinberg equation
p^2 + 2pq + q^2 = 1 p = dominant, q = recessive (p+q=1) relates allele and genotype frequencies in a population Also called an equilibrium under a given set of conditions (allele and genotype frequencies do not change over the course of many generations, especially in LARGE populations)
68
What are the 5 conditions required for a population to be in Hardy-Weinberg equilibrium?
1. No genetic drift - the population is so large that allele frequencies do not change (allele frequencies do not change due to random sampling errors) 2. There is random mating 3. There is no migration 4. There is no natural selection 5. There are no new mutations
69
T/F: In reality, no population completely satisfies the Hardy-Weinberg equilibrium
True However, in some large natural populations there is relatively little migration and negligible natural selection In these cases, the HW equilibrium is nearly approximated for certain genes
70
How can the HW equation can be extended to situations in which a gene exists in 3 or more alleles?
(p+q+r)2=1 --> p2+q2+r2+ 2pq+ 2qr+2pr=1
71
If the chi square value is too high when testing for HW equilibrium, the population would be in _________
disequilibrium Allele frequencies will still add up to 1, but they won't match the expected frequencies very closely
72
If a population is not in HW equilibrium, then one generation of _______________ establishes equilibrium
random mating without selection
73
If in HW equilibrium (large populations), allele and genotype frequencies can be determined from:
frequency of any one homozygous genotype Only in such cases one can assume that genotype frequencies follow the H-W equation
74
Microevolution
describes changes in a population's gene pool from generation to generation Genetic variation in natural populations changes over many generations
75
Microevolution is driven by:
Mutation Genetic drift Migration Natural selection Nonrandom mating
76
________ is the only source of new allelic variation
Mutation
77
Random genetic drift
Random change in allele frequency due to chance In other words, allele frequencies may drift from generation to generation as a matter of chance large effect in small population small effect in large population
78
Random mating
individuals choose their mates regardless of their genotypes and phenotypes in many cases, particularly in human populations, this condition is violated frequently
79
Assortive mating
occurs when individuals are more likely to mate due to similar phenotypic characteristics
80
Disassortative mating
occurs when individuals with dissimilar phenotypes mate preferentially
81
Outbreeding
the mating between genetically-unrelated individuals
82
In the absence of other evolutionary forces, the allele frequencies are not affected by:
in- or out-breeding However, these patterns of mating do disrupt the balance of genotypes that is predicted by the HW equilibrium
83
__________ is the most frequent way that HW is violated
Non-random mating
84
What does the coefficient of inbreeding (F) mean?
percent chance that any gene is homozygous due to a shared ancestor can be computed by analyzing the degree of relatedness within a pedigree
85
What is the equation for coefficient of inbreeding?
F = S(1/2)^n x (1+FA) F is the inbreeding coefficient of the individual of interest n is the number of individuals in the inbreeding path (excluding the inbred offspring) FA is the inbreeding coefficient of the common ancestor S indicates the sum of (1/2)n(1 + FA) for each inbreeding path
86
How do you determine an inbreeding path?
Inbreeding path = the shortest path through the pedigree that includes both parents and the common ancestor The length of each inbreeding path is calculated by adding all the individuals in the path except the individual of interest For example, if IV-1 is inbred, the path would be IV-1 -> [III-2 -> II-2 -> I-2 -> II-3 -> III-3], so the path has five members
87
The coefficient of inbreeding is also called the ________________
Fixation coefficient That explains the symbol F The fixation coefficient is the probability that an allele will be fixed in the homozygous condition
88
How do you calculate genotype frequencies in an inbred population
For example, let’s consider the situation in which the frequencies of A and a are p and q, respectively p^2 + Fpq = frequency of AA 2pq(1 – F) = frequency of Aa q^2 + Fpq = frequency of aa
89
Inbreeding ______ the proportion of homozygotes and __________ that of heterozygotes
increases; decreases In natural populations, the inbreeding coefficient tends to increase as the population size decreases
90
Mutations are random heritable events that occur ___________________
spontaneously at low rates Mutagens increase the mutation rate
91
__________ mutations are those that provide genetic variation to the population
Germline (not somatic)
92
Mutational variability provides the raw material for evolution but does not:
constitute evolution itself Mutation can provide new alleles, but does not act as the major force dictating the final balance
93
A new mutation may be
beneficial, neutral, or deleterious Neutral and deleterious mutations are far likelier to occur than beneficial mutations
94
Why are mutations more likely to be neutral or deleterious than beneficial?
Protein synthesis is very specific, so it is very difficult for a change to have a positive effect
95
How does the mutation rate affect allele frequencies in a population over time?
Consider a gene that exists as a functional allele A (allele frequency denoted by p) A mutation converts A into a nonfunctional allele, a (denoted by q) The mutation A -> a occurs at a rate symbolized by u (the reverse mutation (a -> A) occurs at a negligible rate) The increase in the frequency of the a allele after one generation is (delta)q = up
96
Mutation rate
probability that a gene will be altered by a new mutation Expressed as the number of new mutations in a given gene per generation Commonly in the range of 10^-5 to 10^-6 per generation
97
How to calculate change in allele frequency after any number of generations
(1 - u)^t = pt/p0 u = mutation rate t = number of generations p0 = frequency of allele in the starting generation pt = frequency of allele after t generations
98
In the long run, genetic drift favors:
either the loss or the fixation of an allele The fixed allele is monomorphic and cannot fluctuate The rate depends on the population size
99
How many new mutations do we expect in natural populations?
If each individual has two copies of the gene of interest, then expected number of new mutations = 2Nu u = mutation rate N = number of individuals in the population This means, of course, that a new mutation is more likely to occur in a large population than in a small one
100
How likely is it that a new mutation will be fixed due to random genetic drift?
The probability of fixation of a newly arising allele due to genetic drift is 1/(2N) In other words, the probability of fixation is the same as the allele frequency in the population
101
How likely is it that a new mutation will be eliminated due to random genetic drift?
Probability of elimination = 1 - 1/2N
102
When population size (N) is very large:
New mutations are much more likely to occur However, each new mutation has a greater chance of being eliminated from the population due to random genetic drift
103
When population size (N) is very small:
New mutations are less likely to occur However, each new mutation has a greater chance of being fixed in the population due to random genetic drift
104
If fixation does occur, how many generations is it likely to take?
Ŧ = 4N Ŧ = average number of generations to achieve fixation N = number of individuals in the population, assuming males and females contribute equally to the next generation As expected, allele fixation will take much longer in large populations
105
Genetic drift ultimately operates in a ________ manner with regard to allele frequency
directional In the long run, it leads to either allele fixation or elimination
106
Bottleneck effect
In nature, a population can be reduced dramatically in size by a natural disaster for example Such a disaster randomly eliminates individuals regardless of their genotype The period of the bottleneck, when the population size is very small, may be influenced by genetic drift
107
Founder effect
A small group of individuals (separates from a larger population, or establishes a colony in a new location) This has two important consequences: 1. The founding population is expected to have less genetic variation than the original population 2. The founding population will have allelic frequencies that may differ markedly from those of the original population, as a matter of chance
108
Cancer is a disease characterized by ___________________
uncontrolled cell division it is a genetic disease at the cellular level
109
What are the three main characteristics of cancer?
1. Most cancers originate in a single cell (in this regard, a cancerous growth can be considered to be clonal) 2. At the cellular and genetic levels, cancer is usually a multistep process - it begins with a precancerous genetic change (i.e., a benign growth); following additional genetic changes, it progresses to cancerous cell growth 3. Once a cellular growth has become malignant, the cells are invasive (i.e., they can invade healthy tissues) - they are also metastatic (i.e., they can migrate to other parts of the body)
110
Most cancers are the result of _______________ mutations that accumulate in a single cell (and all daughters)
multiple somatic
111
______% of cancers have in inherited component (IE inherited BRCA-1 mutations and breast cancer)
5-10 Most cancer (90-95%) are not inherited A subset of these is the result of spontaneous mutations and viruses (<5%). Viral: cervical cancer
112
Specific compounds that are known to cause cancer are termed _________
carcinogens
113
Proto-oncogene
gene often found mutated in cancer whose normal function is to regulate cell growth normal cellular gene that can incur a mutation to become an oncogene Expression becomes abnormally active, this is a gain-of-function mutation
114
Oncogene
mutated form of normal gene that helps to promote or allows for the uncontrolled cell growth of cancer
115
Growth factors
bind to cell surface receptors and initiate a cascade of cellular events leading ultimately to cell division Polypeptide hormones that regulate cell cycle in part, epidermal growth factor (EGF) is a growth hormone
116
What are the four main ways proto-oncogenes have been found to occur?
1. Missense mutations 2. Gene amplifications - overexpression, this yields too much of the encoded protein 3. Chromosomal translocations 4. Viral integration
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Tumor-suppressor genes
normal genes that serve to prevent the proliferation of cancer cells If they are inactivated by mutation, it becomes more likely that cancer will occur
118
p53 gene
the second tumor-suppressor gene discovered about 50% of all human cancers are associated with defects in the p53 gene a primary role for the p53 protein is to determine if a cell has incurred DNA damage - if so, p53 will promote three types of cellular pathways to prevent the division of cells with damaged DNA
119
Many cancers begin with a ________ mutation that, with time and more mutations leads to _________
benign, malignancy Furthermore, a malignancy can continue to accumulate genetic changes that make it even more difficult to treat
120
Most inherited forms of cancer involve a defect in _____________
tumor-suppressor gene (ex Brca-1 and breast cancer)
121
Most cancers are related to _______________________
exposure to mutagens these alter the structure and expression of genes