Lecture 7: Multifactorial Disorders Flashcards
A trait that is inherited in a __________ manner is
one that cannot be attributed to a single locus. It is the
result of the additive effect of a number of genetic loci
together with an environmental influence.
A trait that is inherited in a multifactorial manner is
one that cannot be attributed to a single locus. It is the
result of the additive effect of a number of genetic loci
together with an environmental influence
The relative contribution of genetic susceptibility to the predisposition to disease in a population can be is quantified by the _________ of the disease in that population
The relative contribution of genetic susceptibility to the predisposition to disease in a population can be is quantified by the Heritability of the disease in that population.
Higher heritability yield higher instance of disease amongst a family
Polygenetic inherited traits show a _________ distribution
Polygenetic inherited traits show a Normal distribution
Describe the Threshold Model of Multifactorial Disorders
- There is an underlying distribution of susceptibility in the population that follows a normal distribution with most people remaining unaffected
- Individuals will have more or less liability toward the trait depending on how many predisposing alleles they have inherited and the degree to which they are exposed to relevant environmental factors
- The individuals at the low end of distribution have little chance of expressing the trait
- Those at the high end of the distribution have more predisposing genes and environmental factors and are more likely to express the trait
_____________ is the sum of all of the factors which influence the development of the multifactorial disorder (genetic and environmental)
Up to a point a person will not display signs of the trait; when a ______________ is crossed the trait appears
Liability: sum of all of the factors which influence the development of the multifactorial disorder (genetic and environmental)
Up to a point a person will not display signs of the trait; when a Threshold of liability is crossed the trait appears
Estimating Heritability
- _____ Studies –looks at the relative of affected and asks how much more likely it is that they are to be affected compared to an unrelated person
- _____ Studies –compare MZ and DZ twins to see how often co-twin affected – share environment regardless of zygosity
- ______ Studies –separate effects of genes and family environment
Estimating Heritability
- Family Studies –looks at the relative of affected and asks how much more likely it is that they are to be affected compared to an unrelated person
- Twin studies –compare MZ and DZ twins to see how often co-twin affected – share environment regardless of zygosity
- Adoption studies –separate effects of genes and family environment
Term for when both twins show a particular trait?
When only one twin shows a trait?
Concordance
Discordance
__________ Studies compare the frequency of a variant in affected patients versus frequency in a carefully matched control group; if frequency differs significantly between 2 groups then there is evidence for correlation
Association Studies compare the frequency of a variant in affected patients versus frequency in a carefully matched control group; if frequency differs significantly between 2 groups then there is evidence for correlation
__________________________: Identify common, low penetrance susceptibility variants. Rather than looking at one variant you compare variants across entire genome. Purely statistical and not specifically genetic
Genome-Wide Association Studies: Identify common, low penetrance susceptibility variants. Rather than looking at one variant you compare variants across entire genome. Purely statistical and not specifically genetic
The risk of recurrence for multifactorial inherited diseases is higher if more than one family member is affected. T/F
True
Some multifactorial disorders display a sex predilection affecting either males/females more often -recurrence risk is _______ if the afflicted person is of the lesser affected sex (ie. Girl gets a predominantly male afflicting disease)
Some multifactorial disorders display a sex predilection affecting either males/females more often -recurrence risk is higher if the proband is of the lesser affected sex. (ie. Girl gets a predominantly male afflicting disease)
________: Different forms of the same gene?
Allele: Different forms of the same gene
Name a few examples of multifactorial disorders
- Congenital malformations
- Cleft lip and palate; Club foot
- Neural tube defects: Congenital dislocated hip
- Pyloric stenosis; Congenital heart disease
- Common adult diseases
- Diabetes; Coronary heart disease
- Epilepsy; Hypertension
- Mental retardation
- Schizophrenia
- Alcoholism
- Manic depression
Major environmental factor implicated in Neural Tube Defects is maternal ___________ levels which is thought to act via the pathway of homocysteine metabolism
Major environmental factor implicated in Neural Tube Defects is maternal folic acid levels which is thought to act via the pathway of homocysteine metabolism
What genetic defect arises from the common polymorphism C677T (ala222val) which decreases the activity of methylenetetrahydrofolate reductase (MTHFR) resulting in low folate and elevated homocysteine
Neural Tube Defects
What is the most common cause of dementia in the elderly?
What are its two sets of symptoms?
Alzheimer’s Disease
Cognitive
- Memory loss
- Disorientation
Behavioral
- Anxiety
- Delusions
- Depression
- Insomnia
- Wandering
____________ protein is related to the pathology of Alzheimer’s in Down Syndrome patients
Amyloid precursor protein, also related to pathology of Alzheimers in down syndrome patients
Apo E Polymorphisms
APOE2:______________
APOE3:_____________
APOE4:_____________
Apo E Polymorphisms
APOE2: Protective against Alzheimer’s
Decreased Cholesterol
APOE3: Most common Allele
APOE4: Linked to predispose to Alzheimers
Apo E Polymorphisms
APOE2:______________
APOE3:______________
APOE4:______________
Apo E Polymorphisms
APOE2: Protective against Alzheimer’s
Decreased Cholesterol
APOE3: Most common Allele
APOE4: Linked to predispose to Alzheimer’s
Earlier age of onset and more severe disease
Is APOE genetic testing recommended to screen for the risk of Alzheimer’s?
American Society of Human Genetics: it is not recommended for use in routine clinical diagnosis nor should it be used for predictive testing.
This is because AD develops in the absence of APOE ε -4 and because many with APOE ε -4 seem to escape the disease.
