Transcript The Genetic Basis of Complex Inheritance

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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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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
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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
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 Σ ( Xi)
=626/52
=12.04
F2 ave
= 1/n Σ ( Xi)
=626/52
=12.11
F1 var
= 1/(n-1) Σ ( Xi-X)2
=1.29
F2 var
= 1/(n-1) Σ ( Xi-X)2
=4.27
F1 st dev = sqrt(var)
=1.13
F2 st dev = sqrt(var)
=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
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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. 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
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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
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size)
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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