Quantitative Genetics Flashcards
1
Q
Definition
the rate of probability that two people with shared genes will develop the same organic disease
A
Concordance rate
2
Q
Define
Multigenic inheritance
A
characteristic that is specified by a combination of multiple genes
3
Q
Definition
relating to or occurring in a family or its members
A
Familial
4
Q
A risk figure or recurrent risk can be calculated from what?
A
- Diagnosis and mode of inheritance
- Analysis of family pedigree
- Results of rests - linkage studies etc.
5
Q
Define
Conditional probability
A
the probability of an event ( A ), given that another ( B ) has already occurred
6
Q
Define
Discordant
A
showing lack of agreement
7
Q
If the recurrance risk of autism in siblings = 6%
Incidence of autism in general population = 0.1%
What is the relative risk ratio for siblings?
A
60
8
Q
Definition
an increased likelihood of developing a particular disease based on a person’s genetic makeup
A
Inherited predisposition
9
Q
Define
Narrow-sense heritability
A
the degree to which a trait is passed from parent to offspring expressed as the ratio of the additive genetic variance to the total phenotypic variance (VA/VP)
10
Q
What does dominant genetic variance mean?
A
The animals/plants with the desired trait could be homozygous or heterozygous
11
Q
A
12
Q
Define
Index case
A
the first identified case in a group of related cases of a particular communicable or heritable disease
13
Q
Definition
inheriting the same genetic characteristic
A
Concordant
14
Q
How can you estimate narrow-sense heritability?
A
Comparing the offspring values against the averaged value for the two parents (mid-parent value)
15
Q
What are the two common characteristics of quantitative traits?
A
- Many genes contribute to one trait = polygenic or multigenic inheritance
- The trait can be affected by the environment
16
Q
What is heritability?
A
- The proportion of the total phenotypic variation (VP ) in a population that is due to genetic factors
- Different in different environments
17
Q
Define
Monozygotic
A
Twins derived from a single ovum, and so identical
18
Q
A
19
Q
True or False:
Broad-sense heritability considers GxE interactions
A
False
20
Q
Define
Empiric risks
A
The chance that a disease will occur in a family, based on experience with the diagnosis, past history, and medical records rather than theory
21
Q
A
22
Q
Define
Quantitative trait loci (QTL) mapping
A
a statistical method that links two types of information—phenotypic data (trait measurements) and genotypic data (usually molecular markers)—in an attempt to explain the genetic basis of variation in complex trait
23
Q
How can you calculate phenotypic variance (VP) from genotypic (VG ), environmental (VE) and genotype-by-environment interaction (VGxE ) variance?
A
VP = VG + VE + VGxE
24
Q
Definition
when two different genotypes respond to environmental variation in different ways
A
Gene-environment (GxE) interactions
25
# Definition
twins derived from two separate ova, and so not identical
Dizygotic
26
# Define
Dizygotic
twins derived from two separate ova, and so not identical
27
# Definition
studies conducted on identical or fraternal twins. They aim to reveal the importance of environmental and genetic influences for traits, phenotypes, and disorders
Twin studies
28
# Definition
the degree to which a trait is genetically determined expressed as the ratio of the total genetic variance to the phenotypic variance (VG/VP)
Broad-sense heritability
29
# Definition
the degree to which a trait is passed from parent to offspring expressed as the ratio of the additive genetic variance to the total phenotypic variance (VA/VP)
Narrow-sense heritability
30
# Define
Multifactorial traits
traits controlled by multiple genes and the environment
31
# Define
Posterior probability
the statistical probability that a hypothesis is true calculated in the light of relevant observations
32
How many genes would you expect to be involved?
Simplify until 1 individual is on each outer end (already done here)
Add up total simplified individuals (64)
64 = 43
So 3 genes are involved
33
# Definition
a probability as assessed before making reference to certain relevant observations, especially subjectively or on the assumption that all possible outcomes be given the same probability
Prior probability
34
# Define
Twin studies
studies conducted on identical or fraternal twins. They aim to reveal the importance of environmental and genetic influences for traits, phenotypes, and disorders
35
How do you calculate concordance ratio?
MZ concordance / DZ concordance
36
What type of heritability can be used in animal and plant breeding to determine if a population can be changed by selective breeding?
Narrow sense heritability
37
# Define
Concordant
inheriting the same genetic characteristic
38
What methods are used to calculate genetic susceptibility?
1. Population/migration studies
2. Twin studies
3. Family studies
4. Adoption studies
5. Polymorphism associations - mapping
6. Biochemical studies
7. Animal models
39
Twins are considered concordant when?
If they both have the trait in question
40
# Define
Concordance rate
the rate of probability that two people with shared genes will develop the same organic disease
41
42
# Define
Inherited predisposition
an increased likelihood of developing a particular disease based on a person's genetic makeup
43
# Definition
a statistical analysis of pedigree data that investigators use to look for evidence of cosegregation of alleles at a genetic “susceptibility” locus and some known genetic “marker” locus (usually a DNA polymorphism) through generations of families
Linkage analysis
44
# Definition
events that do not impact the probability of each other occurring
Independent events
45
# Define
Genome-wide association studies (GWAS)
an observational study of a genome-wide set of genetic variants in different individuals to see if any variant is associated with a trait
46
What are the 4 steps to Bayesian analysis?
1. Prior probability
2. Conditional probability
3. Joint probability
4. Posterior probability
47
# Definition
a branch of population genetics that deals with phenotypes that vary continuously (in characters such as height or mass)—as opposed to discretely identifiable phenotypes and gene-products (such as eye-colour, or the presence of a particular biochemical)
Quantitative genetics
48
How does risk change with number of affected children in single gene vs mutli gene disorder?
Single gene: risk remains the same regardless of number affected
Multi gene: risk increases with the number affected
49
50
What isn't heritability?
* How much of a trait is genetically determined
* Ho much of an individual's phenotype is due to their genotype
* Fixed for a given trait
51
What is the chance of a child suffering from an autosomal recessive disease if both parents are carriers
25%
52
# Define
Bayesian analysis
a method of statistical inference in which Bayes' theorem is used to update the probability for an hypothesis as more evidence or information becomes available
53
# Definition
a measure of association between an exposure and an outcome. The OR represents the odds that an outcome will occur given a particular exposure, compared to the odds of the outcome occurring in the absence of that exposure
Odds ratio
54
# Definition
Twins derived from a single ovum, and so identical
Monozygotic
55
What does this graph suggest?
G x E interaction is present
56
# Definition
A hypothesis to explain quantitative variation by assuming the interaction of a large number of genes (polygenes) each with a small additive effect on the character
Multiple gene hypothesis
57
# Definition
being related such that each excludes or precludes the other
Mutually exclusive
58
# Definition
statistical approach that is most commonly used to identify susceptibility loci in complex genetic traits
Affected sibling pair (ASP) analysis
59
How do we identify multifactorial disorder genes?
1. Linkage analysis
2. Affected sibling pair analysis (ASP)
3. Genome-wide association studies (GWAS)
60
# Definition
the likelihood that a hereditary trait or disorder present in one family member will occur again in other family members
Recurrence risk
61
# Definition
a disease that is not inherited, nor present at birth, but developing after birth
Acquired disease
62
# Define
Independent events
events that do not impact the probability of each other occurring
63
What does Bayes Theorem consider when calculating the overall probability of an event occurring?
1. All initial possibilities (e.g. carrier status)
2. Additional information (e.g. test results)
64
What does the multiple-gene hypothesis state?
1. A quantitative trait has continuous variation that can be quantified
2. Two or more genes scattered in the genome account for the hereditary influence on the trait in an additive way
3. Each gene locus is occupied by either an additive allele or a non-additive allele
4. The contribution of each additive allele is approximately equal
5. Together, the additive alleles contributing to a single quantitative character produce substantial phenotypic variation
65
# Define
Broad-sense heritability
the degree to which a trait is genetically determined expressed as the ratio of the total genetic variance to the phenotypic variance (VG/VP)
66
# Define
Prior probability
a probability as assessed before making reference to certain relevant observations, especially subjectively or on the assumption that all possible outcomes be given the same probability
67
What does Broad-sense heritability tell us?
Tells us the proportion of the variance in a population within a single generation that is due to genetic factors such as dominance and epistasis
68
Twins are considered discordant when?
If one has the trait and the other does not
69
# Define
Odds ratio
a measure of association between an exposure and an outcome. The OR represents the odds that an outcome will occur given a particular exposure, compared to the odds of the outcome occurring in the absence of that exposure
70
# Define
Familial clustering
the clustering of certain traits, behaviours, or disorders within a given family
71
# Definition
the first identified case in a group of related cases of a particular communicable or heritable disease
Index case
72
# Definition
A physical defect present in a baby at birth that can involve many different parts of the body
Congenital malformations
73
# Define
Heritability
a statistic used in the fields of breeding and genetics that estimates the degree of variation in a phenotypic trait in a population that is due to genetic variation between individuals in that population
74
# Definition
the mean value of the product of the deviations of two variates from their respective means
Covariance
75
# Definition
one of a group of nonallelic genes that together control a quantitative characteristic in an organism
Polygenic
76
How do you calculate relative risk ratio?
77
# Define
Multiple gene hypothesis
A hypothesis to explain quantitative variation by assuming the interaction of a large number of genes (polygenes) each with a small additive effect on the character
78
# Define
Congenital malformations
A physical defect present in a baby at birth that can involve many different parts of the body
79
What does each graph portray?
80
In what conditions is it not possible to arrive at a risk figure using Bayesian analysis?
Multifactorial disorders
Causal heterogeneity
81
# Definition
showing lack of agreement
Discordant
82
# Definition
the probability of an event ( A ), given that another ( B ) has already occurred
Conditional probability
83
# Definition
a statistical measure that calculates the likelihood of two events occurring together and at the same point in time
Joint probability
84
# Definition
the clustering of certain traits, behaviours, or disorders within a given family
Familial clustering
85
# Definition
a statistical method that links two types of information—phenotypic data (trait measurements) and genotypic data (usually molecular markers)—in an attempt to explain the genetic basis of variation in complex trait
Quantitative trait loci (QTL) mapping
86
# Definition
the statistical probability that a hypothesis is true calculated in the light of relevant observations
Posterior probability
87
# Definition
the ratio of the probability of an outcome in an exposed group to the probability of an outcome in an unexposed group
Relative risk ratio
88
# Definition
a method of statistical inference in which Bayes' theorem is used to update the probability for an hypothesis as more evidence or information becomes available
Bayesian analysis
89
How can you estimate whether a trait is heritable?
Look for a correlation between the parents and the offspring
90
# Define
Joint probability
a statistical measure that calculates the likelihood of two events occurring together and at the same point in time
91
# Define
Candidate gene
any gene thought likely to cause a disease
92
# Define
Relative risk ratio
the ratio of the probability of an outcome in an exposed group to the probability of an outcome in an unexposed group
93
# Define
Recurrence risk
the likelihood that a hereditary trait or disorder present in one family member will occur again in other family members
94
How does affected sibling pair analysis determine candidate genes?
If affected siblings inherit a particular chromosome region more or less often than expected by chance, then an allele in that region is involved in some way causing the disease
95
What is the chance of inheriting an autosomal dominant disorder if one parent is a carrier?
50%
96
What does narrow-sense heritability (h2 ) tell us?
Tells us the proportion of genetic variation that is due to additive genetic value (VA)
97
# Definition
an observational study of a genome-wide set of genetic variants in different individuals to see if any variant is associated with a trait
Genome-wide association studies (GWAS)
98
# Define
Linkage analysis
a statistical analysis of pedigree data that investigators use to look for evidence of cosegregation of alleles at a genetic “susceptibility” locus and some known genetic “marker” locus (usually a DNA polymorphism) through generations of families
99
# Definition
any gene thought likely to cause a disease
Candidate gene
100
# Definition
The chance that a disease will occur in a family, based on experience with the diagnosis, past history, and medical records rather than theory
Empiric risks
101
# Define
Acquired disease
a disease that is not inherited, nor present at birth, but developing after birth
102
How do you calculate joint probability?
Prior probability x conditional probability
103
What does fully additive genetic variance mean?
That the animals/plants with the desired trait and all homozygotes
104
# Define
Polygenic
one of a group of nonallelic genes that together control a quantitative characteristic in an organism
105
# Define
Gene-environment (GxE) interactions
when two different genotypes respond to environmental variation in different ways
106
Using Bayes analysis, determine the probability of II-2 being a carrier
107
# Define
Mutually exclusive
being related such that each excludes or precludes the other
108
# Define
Familial
relating to or occurring in a family or its members
109
# Definition
characteristic that is specified by a combination of multiple genes
Multigenic inheritance
110
# Define
Affected sibling pair (ASP) analysis
statistical approach that is most commonly used to identify susceptibility loci in complex genetic traits
111
# Define
Quantitative genetics
a branch of population genetics that deals with phenotypes that vary continuously (in characters such as height or mass)—as opposed to discretely identifiable phenotypes and gene-products (such as eye-colour, or the presence of a particular biochemical)
112
What is the heritability equation (H2)?
H2 = VG/VP
## Footnote
Where:
VG = variation due to genotype
VP = proportion of the total phenotypic variation
113
# Definition
traits controlled by multiple genes and the environment
Multifactorial traits
114
115
# Definition
a statistic used in the fields of breeding and genetics that estimates the degree of variation in a phenotypic trait in a population that is due to genetic variation between individuals in that population
Heritability
