Genetic Basis of Phenotypic Variation

Galton‘s ideology

• invented correlation and regression to measure resemblance

• Found the regression slope of offspring height on mid-parent height is approx 0.8

Mendel vs Galton - what were the differences?

• Mendel describe particulate discrete inheritance

• Galton described continuous inheritance

How did Fisher resolve Mendel‘s and Galton conflict

• showed that if a quantitative trait is influenced by many Mendelian loci, each with a small effect, the combined result is a continuous, approx normal distribution

• All biometrics results are fully compatible with Mendelian inheritance

Infinitesimal model

Mathematical approximation treating traits as affected by infinitely many loci each with an infinitely small effect

Why does adding more loci create a normal distribution?

• with two loci, you get a handful of discrete classes

• Add a third, and there are more classes

• Add more noise and the peaks blur together into a smooth curve

Why do we see continuous variation even with Mendelian loci?

• Polygenic architecture: many loci contribute, shifting the distribution slightly and discrete classes overlap

• Environmental noise: identical genotypes won‘t produce identical phenotypes due to environment eg inbred lab mice can vary in weight

Polygenic trait

• a trait whose phenotypic variation in influenced by alleluia variation at many loci across the genome, each contributing a small effect

• The individuals trait value is approx he sum of all allelic effects

Real life examples of polygenic distribution

• mouse body weight at week 1

• Bill depth in Galapagos finches

• Human height

Difference between gene and alleles in variation

• a gene that regulates body height does not cause variation in body size

• Alleles are the different sequence variants, which may produce slightly different trait values

• Allelic differences at loci cause differences in trait values

Why are the effects of alleles not fixed?

The effect of an allele depends on context

• what the other allele is paired with at the same locus

• Which other loci are present in the same genome e

• The environment the organism develops in

What are the components of total observed phenotypic variance?

Phenotypic variance = genetic variance + environmental variance

Components of genetic variance

Additive + dominance + interaction (epistasis) components

What is narrow sense heritability (h2)?

Va/Vp

• The proposition of phenotypic variance due to additive genetic effects

• determines how much offspring resemble their parents and how fast a trait responds to selection

• Measured by the slope of the offspring-on-midparent regression

• Slope 1.0 = predicted

What is broad sense heritability (H2)?

• Vg/Vp

• The proportion of phenotypic variance due to all genetic effects

• Tells us how much variation is genetic

What is the main distinction between heritable and genetic?

A trait can have genetic basis without offspring resembling parents - this happens when genetic variation does not come from additive effects

When does genetic variation fail to be heritable?

• rare recessive diseases: an affected parent passes a recessive allel but offspring are almost always heterozygous

• Overdominance: the heterozygote has the highest trait value, crossing two homozygotes produce unresembling offspring

• Epistasis: traits depending on specific multi-locus combinations are broken up by recombination

measuring genetic effects at a single locus

Purely additive (codominance) - if heterozygote is exactly between the two homozygotes

Full dominance - if heterozygote matches one homozygotes

Overdominance - If heterozygote exceeds both homozygotes

Real life example of Overdominance

Sickle cell anaemia

• heterozygote have higher fitness in malaria-endemic regions

• Heterozygote trait value exceeds both homozygotes

Why dominance variance is frequency-dependent?

• If A2 is rare - then A2A2 homozygotes are very rare

• Almost all A2 alleles are found in heterozygote

• The effect of carrying one A2 alleles is predictable and behaves almost additvely

What occurs when allele frequencies are equal?

• dominance contributes more to non heritable variances because heterozygote are common

What is shared between parent and offspring?

• receive one allele at each locus from mother and one from father

• Dominance effects do not contribute to parent offspring resemblance

What is shared between siblings?

• can share a who9le diploid genotype if they receive same allele from their mother and same from father Dominance effects

• Dominance can contribute

• This is why sibling resemblance exceeds parent