Lecture 8 Quantitative Genetics

Transcription

1 Lecture 8 Quantitative Genetics CAPMBELL BIOLOGY Chapter 9 Quantitative Genetics How many genes affect a given phenotypic trait e.g. skin color? or How many genes account for the observed variation in a trait? and If its more than one gene what is the relative contribution of each? There are two kinds of variation Physical traits (phenotypes) can show two types of variation a. Discrete variation b. Continuous variation 1

2 1. Discrete Variation The variation shows widely different alternative states Most of the traits we ve so far encountered show discrete variation e.g. Seed shape in pea: either round or wrinkled Wing size in Drosophila Hemophilia in man Flower color in pea Blood groups in man either wild-type or vestigial either normal or hemophiliac either purple or white a person has either one blood group or another: A B AB O Discrete variants are inherited as simple Mendelian traits This kind of variation is caused by the existence of different alleles of a single gene (or locus) There may be two or more alternative alleles: e.g. Human blood groups - One locus but 3 alleles: A, B, O Possible genotypes Phenotypes i.e. Blood group AA A AO A BB B BO B AB AB OO O 2

3 2. Continuous Variation The variation does not show a few discrete alternative states but is found as a continuum in a population e.g. Height in Humans Skin colour Milk yield in cattle IQ (intelligence quotient) Time to run 100m Weight in humans Traits that show continuous variation are often referred to as Quantitative Traits They are called quantitative because they can be given a numerical value e.g. Milk Yield gallons/cow/year Quantitative traits can typically have any value in a wide range i.e. the value shows continuous variation within that range 3

4 Quantitative traits often show large environmental effects e.g. Human height potential is affected by nutritional status in early childhood Skin colour is affected by exposure to sunlight Question: Are quantitative traits inherited and if so, how? Answer: Yes, to a greater or lesser extent depending on the trait This kind of inheritance is called: Quantitative inheritance or Polygenic inheritance Polygenic because typically many genes are involved in determining the value of a quantitative trait Does the way in which Quantitative Traits are inherited differ from the way in which discrete traits are inherited? Answer: No! Quantitative Traits are inherited like any other trait 1920 s Edward East investigated the inheritance of: Flower tube length in tobacco plants He decided to cross plants of two different strains: Strain A Short flower tube length mm Strain B Long flower tube length mm 4

5 Strain A X Strain B 37 43mm mm F1 progeny No. plants narrow range mm Flower length wide range F2 progeny mm From the F2 population, he then selected individuals representing the mean length and the extremes (longest and shortest) and selfed them shortest mean longest 54 X X X 82 F Flower tube length 5

6 From these experiments we can conclude: Flower tube length in the parental strains A and B shows continuous variation The final length values achieved shows wide variation: 37mm (shortest strain A) 97mm (longest strain B) F1 progeny show an intermediate range: 61 67mm (mean: 64) F2 progeny show a very broad range: 52 82mm (mean: 67) Although the range in values has broadened in the F2 population the mean length in the F1 and F2 populations is very similar F3 progeny: parents with longer (or shorter) flowers have offspring that have longer (or shorter) flowers Lots of other traits in plants and animals are inherited in the same way here is another example in plants 6

7 Since the F3 populations show length values that are similar to their F2 parents, it is clear that length is inherited How can we account for the continuous variation observed in trait that shows Quantitative Inheritance? Propose that the trait shows continuous variation because it is determined by several genes and that they have additive effects Skin pigmentation shows enormous variation across the human species How can this be explained genetically? Evidence suggests that at least 3 genes A, B, C determine the level of pigmentation A hypothesis to explain inheritance of skin pigmentation 1. Imagine that for each gene there are 2 alleles: Gene A: A or a Gene B: B or b Gene C: C or c 2. For each gene, one of the alleles (the dark skin allele) is incompletely dominant and has an additive effect of The other allele is recessive ( a, b, and c) and has no effect i.e All the alleles that have an additive effect (i.e. A or B or C) are given the same value Environmental factors (e.g. exposure to sunlight) also has a substantial effect on the final quantitative value of the trait 7

8 There are therefore two possible extremes of pigmentation: An individual homozygous for the dominant alleles of each gene: A A B B C C will have a phenotype that expresses 6 units of darkness and will have the darkest skin colour An individual homozygous for all the recessive alleles of each gene: a a b b c c Because each recessive allele contributes nothing toward skin colour these individuals will have the lightest skin colour Individuals that are heterozygous for each gene (assume genes are unlined): A, a B, b C, c express 3 units of darkness & have an intermediate skin colour Each individual will produce 8 types of gamete (ABC, abc, abc, AbC, ABc, abc, Abc, abc) A large population where most individuals are heterozygous for each of the 3 genes will produce offspring that have: 8 x 8 = 64 possible combinations of the alleles The phenotype of the offspring will have all possible unit values between 0 and 6 This population will show continuous variation in skin colour and the quantitative values will show what is called a normal distribution in the population 8

9 20/64 Fraction 15/64 of the population 6/64 1/ units 9

10 Using brain-imaging the team in UCLA show that the integrity of the myelin deposits which are found surrounding nerve fibres in brain can in part determine the speed with which information is signalled and therefore processed. The faster the signalling, the faster the processing of information. Our genetics can exert some influence on our intelligence by determining how well our nerve axons are encased in myelin sheaths. Chiang et al J Neuroscience 29:

11 The team in UCLA scanned the brains of 23 sets of identical twins & 23 sets of fraternal twins. Identical twins are 100% genetically the same, whereas fraternal twins are 50% similar. The team found that there was evidence that myelin integrity was determined genetically in many parts of the human brain which can influence intelligence. In essence it was more similar identical twins. Of course there are lots of other factors that influence intelligence some of which are environmental so this is just part of the story Chiang et al J Neuroscience 29:

12 A genome-wide association study for coronary artery disease identifies a novel susceptibility locus in the major histocompatibility complex. Davies RW, Wells GA, Stewart AF, Erdmann J, Shah SH, Ferguson JF, Hall AS, Anand SS, Burnett MS, Epstein SE, Dandona S, Chen L, Nahrstaedt J, Loley C, König IR, Kraus WE, Granger CB, Engert JC, Hengstenberg C, Wichmann HE, Schreiber S, Tang WH, Ellis SG, Rader DJ, Hazen SL, Reilly MP, Samani NJ, Schunkert H, Roberts R, McPherson R. Circ Cardiovasc Genet Apr 1;5(2): Epub 2012 Feb 7. 12

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