Week 2 Quantitative Genetics

Week 2 Quantitative Genetics Maps of Genetic Variation Qualitative and Quantitative Variation Qualitative traits - Blood groups, eye colour, flower colour, lead shape (few distinct groups of phenotypes) - Only a few genotypes and differences are clear between them Quantitative traits - Height, weight, protein content etc. - Value of phenotype can fall between a large range Example of Threshold Trait The trait is a complex phenotype but you see two clear categories (people with or without a disease for example). The underlying control of the trait is still complex, multiple genes are involved and the influence of the environment. So there is not always a range of different phenotypes for complex traits. Week 2 Polygenes These traits are controlled by multiple genes and environment. Models of Gene Action - Interaction between alleles at a single locus In what different ways can two alleles interact to determine the phenotype value? Additive Effects Alleles act independently! This is where, the phenotype value is directly proportional to the amount of A2 alleles you have in the case. The A1A1 homozygote has a phenotypic value of 0. The A1A2 heterozygote = 1 The A2A2 homozygote = 2 So, there is a linear value for the phenotypic value with correspondence to the A2 allele. Dominance Effects There is complete dominance of one allele over the other. The heterozygote (A1A2) would have the same phenotype value (2) with the homozygote dominant (A2A2). Week 2 → Sickle cell anaemia: Heterozygote carriers can have an additional selective advantage which protects against malaria, causes overdominance effect. Observed rarely. For complex traits it is difficult to infer the genotype of an individual just by looking at the height for example. Assuming the above graph refers to heights of a plant (controlled by Gene B), a 30cm plant could fall into any of the 3 genotype categories. Hence just by knowing the height (phenotype) of the plant, we cannot immediately know the genotype of the complex trait as it is not as simple as mendelian genetics. Week 2 Genotype X Environment Interaction (G x E) As noted from before, complex traits can also be heavily influenced by the environment they are present in. For example, a plant may change its flowering time based on its surrounding temperature. (a)Shows us the environment does not have an effect on the flowering times of plants (b) Shows us that environment 2 is favourable and higher trait value and the genes respond to the environment shift. Plants flower earlier in environment 2. (c) Some genotypes flower earlier in environment 2 versus 1 and vice versa. Modelling Quantitative Traits Week 2 Modelling Notation A+ adds value to trait A- decreases value of trait → With more than one gene you get 9 possible genotypes However, you cannot map each of these genotypes to a model phenotype. So how can we do this? How many Phenotypes correspond with Genotypes? k = number of genes 2 genes = 9 genotypes = 9 phenotypes? Possible, but not necessarily 9 phenotypes. With ‘k’ genes → 3k genotypes / phenotypes So segregation at ‘k’ genes may only actually produce 2k + 1 phenotypes. Week 2 Model for a Quantitative Trait Case Example - Two different varieties of plants are identical apart from one gene (Gene A). - All P1 individuals are A+A+ - All P2 individuals are AA- P1 phenotypes = taller plants Genetic Model Week 2 Model for ‘1 Gene’ The additive effect (a) is the difference between the homozygotes divided by 2. The mean (m) is the average of the two parents. The dominance effect (d) is the average value of the F1 generate minus the mean. Can be a negative value or positive. Dominance Ratio Statistic Calculation Once values of ‘a’ and ‘d’ are calculated, we can calculate the dominance ratio (d.r.) If d.r. is 1, we hence know that ‘d’ and ‘a’ are equal. This would mean that according to our genetic model, the heterozygote individual has the same average heigh as the A+A+ parent (P1). This would also mean that there is complete dominance of the A+ allele over the A- allele as the heterozygote (A+A-) fully mimics the height of the A+A+ parent. Week 2 Model for ‘2 Genes’ - G1 and G2 Why is the distribution of the two genes in the two parents important? It changes the way we construct our genetic model and use the equations. Looking back at the equations we can see that in both these cases, the equations differ. In the first case across both genes, all the positive alleles are in the same individual. This is known as association. Whereas, dispersion, occurs when the positive and negative alleles are dispersed between both parents. Model for Many Genes There is a balancing effect between positive and negative alleles. We can extend the balancing effect across many genes. In the table: an additive model is created to fill in the effect of individual genes. Overall, we observe the net effect. EXAMPLE QUESTION Week 2 Additive / Dominance Model - What does it mean? If one knew the genotypes, one could write the meaning of e.g. A+A+ B+B- C-C- = m + A1 + D2 (bc heterozygous) - A3 This assumes that the genes do not interact with each other. What is the interaction? No Interaction If we look at the table, we can determine the effects (if any at all) of the A gene on the B gene for example. The difference in phenotype between the two ‘A’ gene homozygotes is the same no matter the B gene genotype. We can conclude that there is no interaction between A and B genes. With Interaction What if the difference in value or trait score between the two A gene homozygotes depends on what the B genotype is? This hints at interaction between A and B gene to affect the phenotype. Week 2 The trait scores between the A gene homozygotes is increasing with B genotype (value of A gene homozygotes if B+B+, is double, compared to B-Bgenotype) QTL Distribution Heritability: How can we estimate it? Week 2 How can we calculate Heritability using a model? Vp = Vg + Ve Total Trait Variance = Genetic Variance + Environmental Variance H2 = Vg / Vp Broad Sense Heritability = Genetic Variance / Total Trait Variance (the proportion of variance that’s due to effect of genes on the trait) This is only true if the genotype and the environment are uncorrelated and all the genotypes experience the same range of environments (e.g. plants in a greenhouse). But organisms like humans move around and are exposed to different environments. Genotype by Environment Correlation - Often the genotype and environment experience a correlation - For example: genotype influences environment Example in Humans (where genotype influences environment) High IQ = Higher income? = Better Job? = Settle in nicer / richer area = Better environment = Children inherit good environment from parents = Helps foster high IQ in children > Cycle Repeats Itself If a trait is highly heritable, you would expect offspring trait values to increase alongside parent trait values (positive regression). Regression may be inflated or influenced by common environment effects which may affect shared traits between the parents and offspring’s.