Introduction to Quantitative Genetics


In principle:

We can extend single-locus  multilocus  quantitative models

1AA : 2Aa : 1 aa (1AnAn : 2Anan : 1anan)n normal distribution

Genotype / Phenotype correlation Heritability
    Genotypic expression depends on environment
    Heritability (h2) estimates proportion of phenotypic variation due to genetic variation  

Genotype / Environmental interaction is variable (& unpredictable)
       The Norm of Reaction describes this

Heritability is not inevitability
    Genetics is not destiny


Variation can be quantified (review)

      mean  standard deviation: 
      variance: 2
      coefficient of variation (CV)  =  (/) x 100

      CV removes effect of size  when comparing variance:
        Ex.: Suppose  X = whale length     Y =  tail width
                X = 100  1.0 versus Y = 1.0  0.1
                CV of X = 1%        CV of Y = 10%
                Y is more variable, though X is larger

      Variation follows "normal distribution" (bell-curve) iff
              Multiple loci are involved  (quantitative)
              Each locus has about equal effect (additive)
              Each locus acts independently
                    [interaction variance (see below) is minimal]
              Ex.: Suppose a trait is influenced by 5 loci, each with two alleles A & a
                      A contributes 2 units to phenotype, a contributes 1 unit
                      Range of contributions = (2u aa : 3u Aa: 4u AA)5
                         mean = 30 units , range 20 ~ 40 units
                               (AaBbCcDdEe) vs (aabbccddeeff ~ AABBCCDDEEFF)
                         35 = 243 genotype classes => variation continuous

Variation has two sources: genetic (2G) & environmental (2E) variance

      phenotypic variance      2P  = 2G2E2GxE
      additive variance            2A  = 2G2E 
      heritability                        h2  = 2G  /  2A  = 2G / (2G2E)

          "heritability in the narrow sense" additive variance
             heritability h2 is the fraction due to variance in genotypes 
                  assumes genotype / phenotype relationship is independent of environment

                 ignores 2GxE  interaction variance:
                       genotype / phenotype relationship differs  in different environments.
                       Ex.: same strain of corn produces different yields in different conditions

       Artificial breeding indicates that organismal variation is highly heritable

             Artificial selection on agricultural species
                  Commercially useful traits can be improved by selective breeding
             Common Garden experiments
             Correlation / Regression analysis
shows association between variables

                    Offspring / midparent correlation estimates heritability
                    Limits of prediction from correlation & regression

            For many traits in many organisms:
                    CV   =     5 ~ 10 %
                     h2    =     0.5 ~ 0.9

             The Norm of Reaction mediates genotype through environment to produce phenotype
                   single-genotype traits
                   two-genotype traits
                  


Genetics & Society

"Is it Genetic?"
       Myth 1: That which is heritable is purely genetic
      
            phenotypic variance      2P  = 2G
                                                  [ignore   2E , 2GxE]

       Myth 2: That which is genetic is fixed & unchangeable

          Ex.: IQ test scores in Homo: h2 0.7 within groups
                  Inter-group differences: environmental and/or genetic?
                 Heritable traits can be modified by environment2GxE is large
                 Heredity, IQ, & Education
 
     See:
         Gray & Thompson. 2004. Neurobiology of intelligence: ethics and science,
             Nature Reviews Neuroscience 5: 471-482.
          Foster 2006. Science & Ethics in the Human Genome Project.
               2001 NCBI International HapMap Project meeting
          American Eugenics Archive

All text material 2013 by Steven M. Carr