Term
| Multifactorial Diseases Facts |
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Definition
Combination of genetic and environment
Applies to most common diseases.
Aggregation in families but no mendelian segregation.
Penetrance is low in multifactorial disorders. |
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Term
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Definition
Modifer genes change age of onset of a disease.
SOD1 mutation -> ALS
CNTF affects age of onset
CNTF heterozygote is unaffected without SOD1 mutation. |
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Term
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Definition
Have to be heterozygous in gene genes. To be affected.
Heterozygous in one = unaffected.
Triallelic inheritence: 3 mutations at 2 loci. Bardet-Biedl syndrome |
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Term
| Most common multifactorial Congenital |
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Definition
Heart defects, NTD, Cleft Lip
Pyloric Stenosis. M:F 5:1
Partly due to altered expression of neuronal nitric oxide synthase(NOS) |
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Term
| Liability Threshold Model |
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Definition
Susceptibility to the disease is a continuous character(having the disease is discontinuous)
Explains he increased risk for family members
More affected family members, more susceptible you are. |
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Term
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Definition
Genetically Determined H^2 = 1
Environmentally Determined H^2 = 0
Multifactorial diseases H^2 = 0.4-0.7 |
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Term
| Ways to determine whether genes have a significant influence on disease |
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Definition
Familial aggregation
Twin studies
Adoption studies |
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Term
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Definition
Test whether the disease in familys is increased over the general population.
Use Chi-Squared test RR should be greater than 1
RR is calculated by. The risk of relatives being affected, divided by the control.
Huntingtons(AD) 50% of siblings are affected.
General population 1:20,000 affected
(1/2) / (1/20000) = RR 10000 |
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Term
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Definition
Dizogotic twins have 50% of genes in common. Same as sibilngs
Monogenic disorder MZ twins - 100% concordance.
DZ twins-50%
Multifactorial. MZ twins -80%
DZ twins- 40%
Proved environment can effect epigenetics |
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Term
| Monogenic Vs Multifactorial Studies |
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Definition
Monogenic: Large families. One disease
gene/family. Highly penetrant genes.
Unaffected invididuals also of use
Multifactorial disorders: Small families, Multiple disease genes/patient
Low penetrance genes, unaffected individuals can also carry susceptibility alleles |
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Term
| Consequences for gene mapping |
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Definition
Monogenic: Parametric(lod score), shared segment, homozygosity
Multifactorial: Non-parametric (affected sib pair) Association studies
in large cohorts of cases and controls
Parametric requires: Mode of
inheritance, Disease gene frequency
Penetrance, affection status and
relation between family members |
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Term
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Definition
Mutationally stable
Frequent: 1/1000 bp
Equally spaced |
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Term
| Linkage vs Association Studies |
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Definition
Linkage: Families, Known pedigree
Large segments of IBD
Association: Population, unrelated,
small regions of DNA sharing, Large #
of genetic markers required. |
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Term
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Definition
Multifactorial
Abnormal response to gluten proteins
Twin studies show important role for
environmental factors(gluten)
Family studies show an important role
of genetics.
HLA-DQ2/8 is a major risk factor for CD |
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Term
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Definition
MultiFactorial
RR 3-4%
4:1 M:F. Sibs are more likely to get/have if a female is affected.
Mutation in RET. Loss of function
RET ligands: GDNF, NRTN, increase risk
of Hirschprung in presence of RET
mutation |
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Term
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Definition
Type 1:
Onset: child hood. Autoimmune vs
B-cells.
Prominent HLA effect
Type 2
Onset: middle/old age
Insulin secretion/resistance.
Environmental impact |
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