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A/a ; B/b - classical dihybrid cross: 9:3:3:1 phenotype ratio

Assuming: dominant - recessive allelic interactions



independent assortment

independent, single gene, determination of a character state


L21

Quantitative Genetics

! !Relax 2 classical assumptions: !


(1)dominance is the only or predominant allele
interaction!
(2) no environmental effects !
Read pp 683-710, Quantitative genetics, broad sense heritability,
narrow sense-heritability and its use in breeding and selection.

Most of the tutorial questions will be posted on the
Moodle site in Tutorial questions for Quantitative
genetics

Note character differences used in a


diploid mutant analysis are classical,
categorical (+, haplosufficient or -, non
functional).


Streisfeld and
Rausher 2008

Holton and
Cornish 1995

Allelic interactions:

Dominance (+ / - or haplosufficient /

non-functional), what if, in this

pathway allelic interactions were

codominant or partially dominant

and every enzyme could produce

more or less product?

1) Intermediate


phenotypes

2) Many of them

3) More variation



Transmission
genetic analysis
starts with
character
definition:
F1 dominance
F2 categorical
or continuous ?



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Categorical variation shows distinct phenotypes


(categories), with no intermediates

Short and tall pea phenotypes

Continuous variation shows a series of


overlapping phenotypic classes

Height in humans (and most characters)

Continuous Variation in Humans


Graph of distribution
of height
Fig. 5.1
among 4995 British women

Alternative Allelic Effects Models -Additive



complete recessive

A1A2

intermediate

dominance

SIZE

small

Small the
effect of 2

similar alleles,
each affects
height in a
small way

full dominance

A1A2

codominance

A1A2

A1A1

intermediate

dominance

(2) Alternatively, the


effects of A2 on size
may be additive, each
allele affects height in
a large way and they
sum- intermediate or
codominance

A2A2

tall

(1) Dominance the effect of one


allele on size may be small (A1)
and not significant when paired
with A2.


Back to the beginning..


Wilhelm Johannsen

Pure lines are
homozygous lines
(A,B,C,D,E). The
distribution of bean
weights are shown

from T.H. Morgan 1919. A


Critique of the Theory of
Evolution. Princeton

Johnannsen called a gene the

special conditions,
foundations and determiners
which are present[in the
gametes] in unique, separate
and thereby independent
ways [by which] many
characteristics of the
organism are specified

(Johannsen 1909, p. 124)

Shortly after Mendels rediscovery !


Mendelist (Bateson) advocated discontinuous
variation.
! !
Darwinists (Galton &Pearson) advocated
continuous variation, and!
Johannsen (1905) introduced the term gene to
distinguish it from pangene taken from Darwins
blending theory of pangenesis.
!
!
Johannsen made the distinction between genotype
(characterized by the mean) and phenotype (including
fluctuating variation around the mean of an inbred
strain). His data indicated that, the phenotype
distributions of different genotypes, when combined
in a population, produced a normal distribution. !
!

If the effects of multiple genes and alleles are strictly additive (rather than fully dominant,

you are assuming a kind of CODOMINANT or partially dominant allelic interactions

(eg. A+ = 2, A- = 1, A+A+ = 4, A-A- = 2, A+A-=3).

1 gene 2 alleles, 3
phenotypes (0.25 big
at 4 units, 0.50
medium at 3 units ,
0.25 small at 2 units)

+

+

-

10

++
big

- +

med

2 genes 2 alleles, = 5 phenotypes. Note that most individuals in a


random breeding population should be medium, and few very big
or very small.

1 character- many states





A+B+



A-B+



A+B-



A-B-

A+B+

8 big

7 med big

7 med big

6 med

A-B+

7 med big

6 med

6 med

5 med small

A+B-

7 med big

6 med

6 med

5 med small

A-B-

6 med

5 med small

5 med small

4 small

-

+ -

med

-small

3 genes , 2 alleles

Assume that each
uppercase allele
contributes one
unit to the
phenotype, the
lower case 0
(dominance).



There are 7
possible
phenotypes.

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(1)Redraw the previous


slide (13) into a
distribution



(2) Unlike classical
phenotypes classes a
phenotype distribution
by itself provides no
information about the
number of genes,
genotype frequencies or
dominance relations
among alleles.

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Classic genetic models assume genetic determinism.



1 gene, 2 alleles, 2 genes, 2 alleles affecting categorical characters.
They are used in pedigrees, some inherited disease models and
population genetics.

Polygenic inheritance patterns: More than 3 genes and more than 3
alleles or, multiple gene determinism of single characters.

Multifactorial inheritance includes environmental effects on continuous
character variation of single characters

Quantitative genetic analyses uses a statistical model to partition
genetic, environmental, their covariance, interactions and random
effects affecting phenotype or character distributions.

There are 2 fundamental assumptions about the


genetics of polygenic traits.

(1) the genes and alleles


determining quantitative traits
are the same as categorical
traits, but each has a relatively
small effect on phenotypic
differences in a population.
Otherwise we assume they act as
independent, classical Mendelian
genes.

(2)The loci are cumulative in
their effect

Note 1 character many states

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There are fundamental assumptions about the genetics


of quantitative traits.

(1) Quantative characters are distributed continuously, rather than as a few
qualitative categories.



(2) The genes determining quantitative traits are the same as categorical traits,
but each has a relatively small (additive) effect on phenotypic differences in a
population. Otherwise we assume they act like independent, classical Mendelian
genes (that typically has large effects on phenotypic differences).

(3)The alleles are cumulative in their effect , although they may not be strictly
additive (i.e. still have small dominance). They generally have small effects on a
phenotype whereas, Mendelian alleles have a major effect.



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Mendelian genes, multifactorial inheritance, environmental effects and


QUANTITATIVE genetics

A character is a specific phenotype trait that can be measured.



A Phenotype consists of all measurable characters, including
proteins, biosynthetic pathways, hair color, height and IQ score.

A Genotype is the state (homozygous, heterozygous, hemizygous) of
all the alleles of a gene affecting a phenotype. Genotypes are inherited
in clones but, are broken up by segregation and zygote recombination.

Environment - cannot be inherited, but it affects phenotypic
expression. An individual's environment should be understood very
broadly, it includes:

(1)the internal environment: epigenetic inheritance, expression of
other genes affecting the physiological environment.

(2) external environment: family, social, biological and physical
environments.

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The quantitative phenotype
distribution is usually treated
as a normal distribution,
because its statistics can be
most easily analyzed and it is a
common shape.

A normal distribution is described by 2 parameters, the mean (central


tendency) and the variance around the mean (the spread of the distribution
or the extent of phenotypic (character) variation in a population. A standard
deviation is the square root of the variance.

= mean
2

= var iance
V = var iance

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Include an environmental effect: 1 gene multiple alleles


Figure 18-16 step 1



Categorical or continuous ?

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Acid phosphatase activity of these 2 genotypes is not a categorical


character (the distribution of effects overlap).

Figure 18-16 step 2



Categorical or
continuous ?

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Figure 18-16 step 3


Quantitative character : The phenotype differences between


genotypes (on average) is smaller than the variation expressed by
any genotype.

Figure 18-16 step 4


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Figure 18-16 step 5


A character distribution is composed of the distributions of the


different genotypes in a population and it is expected to vary
between populations.

Figure 18-16 step 6


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There are fundamental assumptions about the genetics


of quantitative traits.

(1)

Quantative phenotypes are distributed continuously, rather than as


a few qualitative categories.

(2) The genes determining quantitative traits are the same as
categorical traits, but each has a relatively small effect on phenotypic
differences in a population. Otherwise we assume they act like
independent, classical Mendelian genes.

(3) The alleles are cumulative in their effect , although they may
not be strictly additive (i.e. still have small dominance).

(4) Quantitative phenotypes are affected by both genetic and
environmental factors.

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Distribution of seed weight in a homozygous (inbred) line of edible beans


The distribution indicates there is an environmental effect.

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Classic genetic models assume genetic determinism.



1 gene, 2 alleles, 2 genes, 2 alleles affecting categorical characters.
They are used in pedigrees, some inherited disease models and
population genetics.

Polygenic inheritance patterns: More than 3 genes and more than 3
alleles or, multiple gene determinism of single characters.

Multifactorial inheritance includes environmental effects on continuous
phenotype variation (of single characters).

Quantitative genetic analyses uses a statistical model to partition
genetic, environmental, their covariance, interactions and random
effects affecting phenotype or character distributions.

The effects of
genotypic and
environmental
variance
contributing to
the character
distribution
can be
partitioned
into additive
components,
because
variances are
squared.

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2
P

2
G

= +

2
E

Estimating Broad -sense heritability (1)


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2
2
2


P = G + E


Data: estimate VE from clone or strain variance, measure VP

Example: 2 inbred strains crossed, Parental, F1, F2 mean and variance.



The mean height of inbred
strain A is 10 (variance = 1) and inbred
strain B is 8 (variance = 3).



They are crossed and the F1 average height is 9 and the variance is
2.0. The F1 is intercrossed randomly and the F2 mean is 9.5 and
the variance is 5.0.



What is the phenotypic (2P or VP), genotypic (2G or VG) and
environmental variance (2E or VE) of this F2 population ?


Estimating broad sense heritability 2:



Using genetic correlations for an estimate of the
relative importance of genetic differences
(variation) among individuals in a population
regulating a phenotype distribution in a
population.

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Heritability is calculated in different ways, but it always has the same


meaning: the proportion of phenotypic variation in a population that
is governed by genetic (inherited or transmitted) effects.

(1) Expected heritability, based on familial relationships:

There is a genetic correlation among individuals in a family (relatives)
due to their high proportion of shared alleles (100%, 50%, 25% etc.).

TRC is one of several fingerprint characters.

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Correlation in height between monozygotic twins (r = 0.84)


Expected ?
2
2
2
P = G + E
Difference due to ?

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Intelligence Quotient:

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In the late 1800s there were 2 different views of intelligence:



(1) Francis Galton, a population biologist who thought there was a
general intelligence, inherited and largely related to the central nervous
system (g).

(2) Alternatively Alfred Binet, a psychologist and educator thought that
intelligence was the average of a number of distinct abilities (polygenic),
that could be altered by teaching style and content (an environmental
effect).

Genetic Correlation in IQ Measurements 

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IQ tests , score word use, number problems, memory processes, spatial


configuration matrices and reaction times and are thought to measure
both cognitive abilities and a general inherited intelligence.

Broad sense heritability


Narrow sense heritability


VG
VG
H =
=
(VG + VE ) (VP )
2

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VA
h =
VE + (VA + VGxE + VD )
2

There are genetic effects that are inherited in monozygotic twins,


clones or inbred strains where there is no recombination, but are not
inherited when sex recombines different genomes. In the numerator of
broad sense heritability (H2), VG includes dominance (VD) and
interaction (VGE) that can represent key sources
genotype/ environment
of phenotypic variation.



In sexual populations, additive genetic variation VA is the only inherited
source of variation in the numerator of narrow sense heritability (h2), the
rest is environmental interactions between alleles (VD ) genes (epistasis)
or genes and their internal or external environments (VGE).

Different kinds of twin and other familial studies find that IQ heritability estimates
center on 0.75 (Nessier et al. 1996. American Psychologist 51: 77 - 101), although the
range is from 0.4 to 0.9. This suggest that variation due to environmental differences
(education) has less influence on IQ than inheritance.

The problem with this argument is the progressive gains in IQ scores, about 6 IQ points
per decade (Flynn, J.R. 1999 Am. Psychologist 54 5-20). How would you explain this ?

Note : the differences


between countries indicate
how the tests were
standardized.

With 6 points per decade
over 10 decades..

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