1. 15 The Genetic Basis of Complex Inheritance

2. 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

3. 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

4. Quantitative Inheritance
Continuous traits = continuous gradation from one phenotype to the next (height)
Categorical traits = phenotype is determined by counting (hen’s eggs)
Threshold traits = only two, or a few phenotypic classes, but their inheritance is determined by multiple genes and environment (adult-onset diabetes)

5. Multiple gene hypothesis:
range of phenotypes can be accounted for by cumulative effect of many alleles.
Polygenes: Additive allele; nonadditive allele
1 phenotypic traits can be measured eg. weight or height
2 two or more loci (genes) could account for phenotype in an additive or cumulative way
3 each loci may be occupied by an additive allele, which contributes a constant amount to the phenotype, or a nonadditive allele which does not
4 The contribution by each allele
may be small and is approx equal
5 together the alleles contribute to a single phenotypic character with substantial variation.

7. Distributions
Distribution of a trait in a population = proportion of individuals that have each of the possible phenotypes
Mean = peak of distribution
x = ∑xi /N
Variance = spread of distribution estimated by squared deviation from the mean s2=∑(xi - x )2/N-1
Standard deviation = square root of the variance
s =√ s2

8. Normal Distribution
Normal distribution = symmetrical curve produced by data in which half points are above and half points are below mean
~68% of a population have a phenotype within one standard deviation (s) of the mean
~95% - within 2 s
~99.7% - within 3 s
• The distribution of a trait in a population implies nothing about its inheritance

9. Fig. 15.5

10. Phenotypic Variation
Variation of a trait can be separated into genetic and environmental components
Genotypic variance sg2 = variation in phenotype caused by differences in genotype
Environmental variance se2 = variation in phenotype caused by environment
Total variance sp2 = combined effects of genotypic and environmental variance
sp2 = sg2 + e2
+ 2 cov ge

11. Analysis of a quant trait: Tomato fruit P1 ave=6oz P2 ave=18oz
F1 ave = 1/n Σ ( Xi)
=626/52
=12.04
F1 var = 1/(n-1) Σ ( Xi-X)2
=1.29
F1 st dev = sqrt(var)
=1.13
F2 ave = 1/n Σ ( Xi)
=626/52
=12.11
F2 var = 1/(n-1) Σ ( Xi-X)2
=4.27
F2 st dev = sqrt(var)
=2.06

12. Phenotypic Variation
Genotype and environment can interact or they can be associated
Genotype-environment (G-E) interaction = environmental effects on phenotype differ according to genotype
Genotype-by-sex interaction: same genotype produces different phenotype in males and females (distribution of height among women and men)

13. Genetic Variation D = difference between parental strains
Genotype-environment (G-E) association = certain genotypes are preferentially associated with certain environments
There is no genotypic variance in a genetically homogeneous population sg2 = 0
When the number of genes affecting a quantitative trait is not too large, the number, n, of genes contributing to the trait is
n = D2/8sg2
D = difference between parental strains

14. Fig

15. Broad-Sense Heritability
Broad-sense heritability (H2) includes all genetic effects combined
H2 = sg2 / sp2 = sg2 / sg2 + se2
Knowledge of heritability is useful in plant and animal breeding because it can be used to predict the magnitude and speed of population improvement

16. Heritability: Twin Studies
Twin studies are often used to assess genetic effects on variation in a trait
Identical twins arise from the splitting of a single fertilized egg = genetically identical
Fraternal twins arise from two fertilized eggs = only half of the genes are identical
Theoretically, the variance between identical twins would be equivalent to se2 , and between fraternal twins - sg2/2 + se2

17. Heritability: Twin Studies
Potential sources of error in twin studies of heritability:
Genotype-environment interaction increases the variance in fraternal twins but not identical twins
Frequent sharing of embryonic membranes by identical twins creates similar intrauterine environment
Greater similarity in treatment of identical twins results in decreased environmental variance
Different sexes can occur in fraternal but not identical twins

18. Narrow-Sense Heritability
Narrow-sense heritability (h2) = proportion of the variance in phenotype that is transmissible from parents to offspring. The genetic variance can be split into both additive and dominant alleles.
h2 = sg2 / sp2 = sg2 / sa2 + sd2 + se2
Narrow-sense heritability can be used to predict changes in the population mean in with individual selection
h2 = (M’ - M)/(M* - M)
In general, h2 < H2 . They are equal only when the alleles affecting the trait are additive in their effects = heterozygous phenotype is exactly intermediate between homozygous dominant and recessive

19. Artificial Selection
Artificial selection =“managed evolution” = the practice of selecting a group of organisms from a population to become the parents of the next generation
h2 is usually the most important in artificial selection
Individual selection = each member of the population to be selected is evaluated according to its individual phenotype
Truncation point = arbitrary level of phenotype that determines which individuals will be used for breeding purposes

20. Artificial Selection
There are limits to the improvement that can be achieved by artificial selection:
Selection limit at which successive generations show no further improvement can be reached because natural selection counteracts artificial selection due to indirect harmful effects of selected traits (weight at birth versus viability)
Correlated response = effect of selection for one trait on a non-selected trait (number of eggs and their size)

21. Inbreeding Inbreeding can have harmful effects
Inbreeding depression = decrease in fitness due to harmful recessive alleles which become homozygous
Heterosis = hybrid vigor refers to superior fitness of heterozygote; often used in agricultural crop production
Fig

22. Correlation Between Relatives
Genetic variation is revealed by correlations between relatives
Covariance (Cov), the tendency for traits to vary together, is Cov(x,y)=∑fi(xi - x )(yi - y )/N-1
Correlation coefficient (r) = statistical evaluation of paired data (pairs of parents, twins, parent and offspring)
r =Cov(x,y)/sxsy
Covariance and correlation coefficient are important in heritability estimates

23. Correlation Between Relatives
Correlation coefficient of a trait between relatives is related to the narrow- or broad-sense heritability

24. Threshold Traits: Heritability
Liability = quantitative trait that presents a genetic risk for a threshold trait
Individuals with a liability above threshold develop the trait
The risk of manifesting a threshold trait has H2 and h2 that cannot be estimated directly, but can be inferred from the incidents of the trait among individuals and their relatives

25. Threshold Traits: Heritability
Many congenital abnormalities are inherited as threshold traits
Heritability analyses can be used to determine recurrence risks
Theoretical curves show incidence, type of inheritance and risk among first-degree relatives of an affected individual

26. Multifactorial Disorders
Most common disorders in human families are multifactorial
Pedigree studies of genetic polymorphisms
are used to map loci for quantitative traits
Quantitative trait locus (QTL) = gene that affects a quantitative trait
Simple tandem repeat polymorphisms (STRPs) are used to locate QTLs
Candidate gene = gene for which there is some a priori basis for suspecting that it affects the trait