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17 Cards in this Set
- Front
- Back
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Define "complex" genetic disease
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It is not possible to ascertain a mode of inheritance for a disease that appears to "run in the family"
(this is true for most genetic diseases) |
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What does it mean when you say that complex disorders are "multifactorial" in nature?
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Disease development requires more than one gene (polygenic) and/or specific environmental factors.
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"multifactorial" genetic disorders
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May have a single major locus malfunction
and/or May have many genes, with minor influences, converging under the right environmental factors NOTE: in this case, no one gene is essential |
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"Susceptibility" genes
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a gene whose mutation(s) may increase the RISK of a person to develop the disease phenotype
NOTE: these genes may neither be sufficient or necessary for the development of the phenotype |
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What do we LOOK for to asses that the disease is genetic?
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-Family clustering
-clustering of the disease in populations that share the same ancestry -greater risk of disease development in monozygotic twins (share 100% genetic info) vs. dizygotic twins -presence of disease in siblings of affected persons -1st degree relatives with disease |
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Define "complex" genetic disease
|
It is not possible to ascertain a mode of inheritance for a disease that appears to "run in the family"
(this is true for most genetic diseases) |
|
|
What does it mean when you say that complex disorders are "multifactorial" in nature?
|
Disease development requires more than one gene (polygenic) and/or specific environmental factors.
|
|
|
"multifactorial" genetic disorders
|
May have a single major locus malfunction
and/or May have many genes, with minor influences, converging under the right environmental factors NOTE: in this case, no one gene is essential |
|
|
"Susceptibility" genes
|
a gene whose mutation(s) may increase the RISK of a person to develop the disease phenotype
NOTE: these genes may neither be sufficient or necessary for the development of the phenotype |
|
|
What do we LOOK for to asses that the disease is genetic?
|
-Family clustering
-clustering of the disease in populations that share the same ancestry -greater risk of disease development in monozygotic twins (share 100% genetic info) vs. dizygotic twins -presence of disease in siblings of affected persons -1st degree relatives with disease |
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What are the more "rigorous" ways to asses that the disease is genetic?
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-concordance:
both twins of a pair are affected = concordance if only 1 of the twins is affected -λ: measure of familial clustering of a disease relative to the population |
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Calculate and interpret λ
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λ= (incidence of disorder in a family relative)/ (incidence of the disorder in the general population)
↑λ= more family relationship ↓λ= less family relationship |
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Calculate and interpret concordance
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C/(D+C)
C= total number of concordant twins D= total number of disconcordant twins High concordance value = high genetic liability Low concordance value = low genetic liability |
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features of finding genes in complex genetic diseases (where ancestry is available)
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-Linkage analysis (use polymorphic markers)
-Can't use Mendelian analysis because there are no large families available -Most common analysis is affected sib pair (ASP) based on identity by descent (ibd: looking at how many alleles siblings share) |
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ratio of sharing of 2 alleles : sharing 1 allele : sharing no alleles
and what does it mean when you see unexpected frequencies? |
25 : 50 : 25
when sharing of alleles occurs at frequencies greater than expected, there is a good chance the marker is located in that area |
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Features of finding gene in complex genetic disorders (using population analysis)
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is is called ASSOCIATION (not linkage)
looks for the co-occurrence of alleles of a particular marker with a disease phenotype in large populations NOTE: must confirm results in several independent populations |
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Crohn's Disease
(Example of association analyses) |
CARD15 is seen in patients with Crohn's disease and in normal people
this means that CARD15 is a "susceptibility" gene Conclusion: CARD15 is one of many factors contributing to Crohn's disease |
