Genomics

1. Genomics Quantitative traits Lecture 13 By Ms. Shumaila Azam

2. Quantitative Traits • Mendel worked with traits that were all discrete, either/or traits: yellow or green, round or wrinkled, etc. Different alleles gave clearly distinguishable phenotypes. • However, many traits don’t fall into discrete categories: height, for example, or yield of corn per acre. These are “quantitative traits”. • The manipulation of quantitative traits has allowed major increases in crop yield during the past 80 years. This is an important part of why today famine is rare. Until very recently, crop improvement through quantitative genetics was the most profitable aspect of genetics. • Early in the history of genetics is was argued that quantitative traits worked through a genetic system quite different from Mendelian genetics. This idea has been disproved, and the theory of quantitative genetics is based on Mendelian principles.

3. Quantitative Traits • Quantitative traits refer to phenotypes (characteristics) that vary in degree and can be attributed to polygenic effects, i.e., product of two or more genes, and their environment.

4. Types of Quantitative Trait 1. continuous trait: can take on any value: height, for example. 2. countable (meristic) can take on integer values only: number of bristles, for example. 3. threshold trait: has an underlying quantitative distribution, but the trait only appears only if a threshold is crossed.

5. Quantitative Traits are Caused by Mendelian Genes • In 1909 Herman Nilsson-Ehle from Sweden did a series of experiments with kernel color in wheat. • Wheat is a hexaploid, the result of 3 different species producing a stable hybrid. There are thus 3 similar but slightly different genomes contained in the wheat genome, called A, B, and D. • Each genome has a single gene that affects kernel color, and each of these loci has a red allele and a white allele. We will call the red alleles A, B, and D, and the white alleles a, b, and d. • Inheritance of these alleles is partially dominant, or “additive”. The amount of red pigment in the kernel is proportional to the number of red alleles present, from 0 to 6.

6. Wheat Kernel Color • The cross: AA BB DD x aa bb dd. Red x white. • F1: Aa Bb Dd phenotype: pink, intermediate between the parents. Now self these. • F2: alleles follow a binomial distribution: • 1/64 have all 6 red alleles = red • 6/64 have 5 red + 1 white = light red • 10/64 have 4 red + 2 white = dark pink • 15/64 have 3 red + 3 white = pink • 10/64 have 2 red + 4 white = light pink • 6/64 have 1 red + 5 white = very pale pink • 1/64 have all 6 white = white • Add a bit of environmental variation and human inability to distinguish similar shades: you get a quantitative distribution. • This demonstrates that a simple Mendelian system: 3 genes, 2 alleles each, partial dominance--can lead to a quantitative trait.

7. More Wheat Kernel Color

8. Multifactorial Traits • Multifactorial traits are determined by multiple genetic and environmental factors acting together • Multifactorial = complex traits = quantitative traits • Most traits that vary in the population, including common human diseases with the genetic component, are complex traits • Genetic architecture of a complex trait = specific effects and combined interactions of all genetic and environmental factors

9. Quantitative Inheritance • Quantitative traits = phenotypes differ in quantity rather than type (such as height) • In a genetically heterogeneous population, genotypes are formed by segregation and recombination • Variation in genotype can be eliminated by studying inbred lines = homozygous for most genes, or F1 progeny of inbred lines = uniformly heterozygous • Complete elimination of environmental variation is impossible

10. Quantitative trait Locus • A quantitative trait locus (QTL) is a region of DNA that is associated with a particular phenotypic trait. • These QTLs are often found on different chromosomes. • Knowing the number of QTLs that explains variation in the phenotypic trait tells us about the genetic architecture of a trait. • QTLs underlie continuous traits (those traits that vary continuously, e.g. height) as opposed to discrete traits (traits that have two or several character values, e.g. red hair in humans, a recessive trait, or smooth vs. wrinkled peas used by Mendel in his experiments). • Generally a single phenotypic trait is usually determined by many genes. Consequently, many QTLs are associated with a single trait.

11. Quantitative trait loci (QTLs) are stretches of DNA containing or linked to the genes that underlie a quantitative trait. • Mapping regions of the genome that contain genes involved in specifying a quantitative trait is done using molecular tags • AFLP • SNPs etc.

12. Uses • It may tell us that plant height is controlled by many genes of small effect, or by a few genes of large effect. • Another use of QTLs is to identify candidate genes underlying a trait. • Once a region of DNA is identified as contributing to a phenotype, it can be sequenced. • The DNA sequence of any genes in this region can then be compared to a database of DNA for genes whose function is already known.

13. Classical QTL analyses are combined with gene expression profiling i.e. by DNA microarrays. • describe cis- and trans-controlling elements for the expression of often disease-associated genes.