Transcript Ch. 16: Presentation Slides

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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 (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)
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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 = ∑fixi /N
• Variance = spread of distribution estimated by
squared deviation from the mean s2=∑fi(xi - x )/N-1
• Standard deviation = square root of the variance
s =√ s2
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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
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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
s p 2 = s g 2 + s e2
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Fig. 15.9
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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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Fig. 15.10
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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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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
• 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
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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)
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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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