GED L16 Notes Flashcards
Contrast Mendelian & Complex traits
Mendelian Vs. Complex Traits - Mendelian: Single gene (monogenic) High penetrance Predictable inheritance Simple relationship Genotype & phenotype Eg. Cystic fibrosis - Complex: (Multifactoral / quantitative) Multiple genes (polygenic) Low penetrance Familial clustering Unpredictable inheritance Complex relationship Genotype & phenotype Strongly influenced by environment (Multifactoral) Prevalence -> ~600/1000 Eg. Alzheimers, Autism, Crohn’s, Athsma, Cleft lip, Coronary Heart Disease, Diabetes, Neural Tube defects / spina bifida
Describe Mendelian traits
- Mendelian: Single gene (monogenic) High penetrance Predictable inheritance Simple relationship Genotype & phenotype Eg. Cystic fibrosis
Describe complex traits
- Complex: (Multifactoral / quantitative) Multiple genes (polygenic) Low penetrance Familial clustering Unpredictable inheritance Complex relationship Genotype & phenotype Strongly influenced by environment (Multifactoral) Prevalence -> ~600/1000 Eg. Alzheimers, Autism, Crohn’s, Athsma, Cleft lip, Coronary Heart Disease, Diabetes, Neural Tube defects / spina bifida
Give an example illustrating genetic & environmental influences on complex traits
• Genetic & Environmental Influences -> Complex Traits:
Eg. Type 2 Diabtetes
~ 6-8% population
Genetic: One affected parent -> 15%
Both parents affected -> 75%
Environment: BMI >30 -> 20%
Describe analysis of quantitative, complex traits
- Quantitative Traits: >Quantitative / continuous traits Complex traits Eg. Height, Blood Pressure, Serum, Cholesterol, BMI, Crop yield Mean: Arithmetic Average (Centre of Distribution) Variance: Spread of values around mean.
What are quantitative traits?
- Quantitative Traits:
>Quantitative / continuous traits
Give an example of quantitative complex traits?
Eg. Height, Blood Pressure, Serum, Cholesterol, BMI, Crop yield
What is the mean?
Mean:
Arithmetic Average (Centre of Distribution)
What is the variance?
Variance:
Spread of values around mean.
What kind of graph / chart can be used to analyse quantitative, complex traits?
Normal distribution curve
Describe analysis of discontinuous, complex traits
- Discontinuous Traits:
>Distcontinuous / Discrete traits
-> Disease / Trait is either present or not present
Complex traits
Threshold Model:
Underlying continuous liability (genetic & environmental factors)
» Threshold above which disease / trait is present
Families with incr. risk of trait / disease
» Distribution of liability shifted towards threshold.
What are discontinuous traits?
- Discontinuous Traits:
>Distcontinuous / Discrete traits
-> Disease / Trait is either present or not present
What is used to analyse discontinuous, complex traits & describe how?
Threshold Model:
Underlying continuous liability (genetic & environmental factors)
» Threshold above which disease / trait is present
Families with incr. risk of trait / disease
» Distribution of liability shifted towards threshold.
What is used to analyse discontinuous, complex traits?
Threshold model
Describe the way in which discontinuous & continuous traits are analysed
- Continuous & discontinuous traits
Same underlying aetiology.
What is the polygene hypothesis?
Genetic basis of complex traits
How is the polygene hypothesis measured?
- Nature vs. nurture:
Proportion of phenotypic variation in quantitative trait that is genetic or environmental.
What is nature vs. nurture in regards to the polygene hypothesis?
- Nature vs. nurture:
Proportion of phenotypic variation in quantitative trait that is genetic or environmental.
What is the equation used to find the total phenotypic variance?
VP = VG + VE
Total Phenotypic Variance = Genetic Variance + Environmental Variance
» VP can also be shown as VT
Describe how to calculate the total phenotypic variance?
VP = VG + VE
Total Phenotypic Variance = Genetic Variance + Environmental Variance
» VP can also be shown as VT
What is heritability?
Proportion of phenotypic variance due to genes
Describe heritability
Heritability
Proportion of phenotypic variance due to genes
H2 = VG / VP
H2 -> value between 0 – 1
High heritability
»_space; Genetic differences in population
»_space; High proportion of phenotypic variation
-» Easier to identify genetic variants associated with trait than using
traits with low heritability.
Estimating Heritability:
» Twin Heritabilty Studies:
1. Identical (monozygotic twins ; MZ)
Share same environment & all alleles
Relatedness ; r = 1
2. Non-identical (dizygotic twins ; DZ)
Share same environment & half of their alleles
Relatedness ; r = 0.5
If MZ twins resemble more than DZ twins ; genes contribute to
variation in trait .
> Assumes equal environmental effects
»_space; Twin Concordance Studies:
Concordance:
Probability a twin is affected by a particular trait if their twin is
affected.
> Concordance = 1.0 -> Other twin always affected
= 0.6 -> 60% chance other twin affected.
Difference in concordance between MZ & DZ twins used to estimate hertitability.
Eg. MZ concordance = 0.50 (50%) ; DZ = 0.08 (8%)
Heritability = 0.85
Heritability Estimates in Humans:
Autism -> 0.4 - 0.9
BMI -> 0.5 – 0.9
Crohn’s -> 0.75
Height -> 0.6 – 0.8
IQ -> 0.3 – 0.8
T1 Diabetes -> 0.9
T2 Diabetes -> 0.4 – 0.8
High heritability does not mean genetic determination. Differences between groups with high heritability for a trait are not the result of genetic differences.
What is the equation used to calculate heritability?
H2 = VG / VP
Describe how the value of heritability can be interpreted
H2 = VG / VP H2 -> value between 0 – 1 High heritability >> Genetic differences in population >> High proportion of phenotypic variation