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The Genetic Basis of


Complex Inheritance

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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
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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
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Quantitative Inheritance
Continuous traits = continuous gradation from one
phenotype to the next (height)

Categorical traits = phenotype is determined by


counting (hens eggs)

Threshold traits = only two, or a few phenotypic


classes, but their inheritance is determined by
multiple genes and environment (adult-onset
diabetes)

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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.
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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 7
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
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Fig. 15.5 9
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 + se2 + 2 cov ge

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Analysis of a quant trait: Tomato fruit
P1 ave=6oz P2 ave=18oz

F1 ave = 1/n ( Xi) F2 ave = 1/n ( Xi)


=626/52 =626/52
=12.04 =12.11

F1 var = 1/(n-1) ( Xi-X)2 F2 var = 1/(n-1) ( Xi-X)2


=1.29 =4.27

F1 st dev = sqrt(var) F2 st dev = sqrt(var)


=1.13 =2.06

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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)

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Genetic Variation
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
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Fig. 15.10 14
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

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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
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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
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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 18
between homozygous dominant and recessive
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

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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) 20
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. 15.14

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

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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

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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

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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
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