L21Biol261Qgenetics2014

8/9/2019 L21Biol261Qgenetics2014

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L21 Quantitative Genetics Relax 2 classical assumptions :

(1) dominance is the only or predominant alleleinteraction

(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 theMoodle site in

Tutorial questions for Quantitativegenetics

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


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Allelic interactions:Dominance (+ / - or haplosufcient /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


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Transmissiongenetic analysis

starts withcharacter

denition:F 1 dominanceF 2 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 ofoverlapping phenotypic classes Height in humans ( and most characters )

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Continuous Variation in Humans

Fig. 5.1

Graph of distribution of heightamong 4995 British women

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Alternative Allelic Effects Models - Additive

small tall

A1A1 A2A2

full dominance A1 A 2

codominance

Small theeffect of 2 similar alleles,each affectsheight in asmall way

SIZE

(1) Dominance the effect of oneallele on size may be small (A 1)and not signicant when pairedwith A

2.

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(2) Alternatively , theeffects of A 2 on sizemay be additive , each

allele affects height ina large way and theysum- intermediate orcodominance

A1 A 2 intermediate dominance

A1 A 2 intermediate dominance

complete recessive


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Back to the beginning..


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Wilhelm Johannsen

Pure lines are

homozygous lines(A,B,C,D,E). Thedistribution of beanweights are shown

Shortly after Mendel

s rediscovery

Mendelist (Bateson) advocateddiscontinuousvariation.

Darwinists

(Galton &Pearson) advocatedcontinuous variation , and

Johannsen (1905) introduced the term

gene

todistinguish it from pangene

taken from Darwin

sblending theory of pangenesis.

Johannsen made the distinction between genotype(characterized by the mean ) and phenotype ( including

uctuating variation around the mean of an inbredstrain ). His data indicated that, the phenotypedistributions of different genotypes, when combined

in a population, produced a normal distribution.

from T.H. Morgan 1919. ACritique of the Theory of

Evolution. Princeton

Johnannsen called a gene thespecial conditions,

foundations and determinerswhich are present[in thegametes] in unique, separateand thereby independentways [by which] manycharacteristics of theorganism are specied(Johannsen 1909, p. 124)


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+ -

+ ++big

+ -

med

- - + med - -small

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

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

2 genes 2 alleles, = 5 phenotypes. Note that most individuals in arandom breeding population should be medium, and few very bigor very small.

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).

10

1 character- many states


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3 genes , 2 alleles Assume that eachuppercase allelecontributes oneunit to thephenotype, the

lower case 0(dominance).

There are 7possible

phenotypes.

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(1) Redraw the previousslide (13) into adistribution

(2) Unlike classicalphenotypes classes a

phenotype distributionby itself provides noinformation about thenumber of genes, genotype frequencies or

dominance relationsamong 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 andpopulation genetics.

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

Multifactorial inheritance includes environmental effects on continuouscharacter variation of single characters

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

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(1) the genes and allelesdetermining quantitative traitsare the same as categorical

traits , but each has a relativelysmall effect on phenotypicdifferences in a population .Otherwise we assume they act asindependent, classical Mendeliangenes.

(2)The loci are cumulative intheir effect

Note 1 character many states

There are 2 fundamental assumptions about thegenetics of polygenic traits .

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(1) Quantative characters are distributed continuously , rather than as a fewqualitative 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 apopulation . 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 strictlyadditive (i.e. still have small dominance). They generally have small effects on a

phenotype whereas, Mendelian alleles have a major effect.

There are fundamental assumptions about the geneticsof quantitative traits .

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Mendelian genes, multifactorial inheritance, environmental effects andQUANTITATIVE genetics

A character is a specic 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 inheritedin clones but, are broken up by segregation and zygote recombination .

Environment - cannot be inherited, but it affects phenotypicexpression. An individual's environment should be understood verybroadly, it includes:

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

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

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The quantitative phenotypedistribution is usually treatedas a normal distribution ,

because it

s statistics can bemost easily analyzed and it is acommon shape.

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A normal distribution is described by 2 parameters, the mean (centraltendency) and the variance around the mean (the spread of the distributionor 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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Figure 18-16 step 1

19 Include an environmental effect: 1 gene multiple alleles

Categorical or continuous ?


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Figure 18-16 step 2

Acid phosphatase activity of these 2 genotypes is not a categoricalcharacter ( the distribution of effects overlap ).

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Categorical or

continuous ?


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Figure 18-16 step 3

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Figure 18-16 step 4

Quantitative character : The phenotype differences between genotypes (on average) is smaller than the variation expressed byany genotype.

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Figure 18-16 step 5

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Figure 18-16 step 6

A character distribution is composed of the distributions of thedifferent genotypes in a population and it is expected to varybetween populations.

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(1) Quantative phenotypes are distributed continuously , rather than asa few qualitative categories .

(2) The genes determining quantitative traits are the same ascategorical traits, but each has a relatively small effect on phenotypic

differences in a population . Otherwise we assume they act likeindependent, classical Mendelian genes.

(3) The alleles are cumulative in their effect , although they maynot be strictly additive (i.e. still have small dominance).

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

There are fundamental assumptions about the geneticsof quantitative traits .

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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 andpopulation genetics.

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

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

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

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The effects ofgenotypic and

environmentalvariancecontributing tothe characterdistribution

can be partitionedinto additivecomponents,becausevariances aresquared.

" P

2= "

G

2+ "

E

2

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Data: estimate V E from clone or strain variance, measure V P Example : 2 inbred strains crossed, Parental, F 1, F 2 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 F 1 average height is 9 and the variance is2.0. The F 1 is intercrossed randomly and the F 2 mean is 9.5 andthe variance is 5.0.

What is the phenotypic ( ! 2P or V P), genotypic ( ! 2G or V G) andenvironmental variance ( ! 2E or V E) of this F 2 population ?

" P

2= "

G

2+ "

E

2

29 Estimating Broad -sense heritability (1 )


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Estimating broad sense heritability 2 :Using genetic correlations for an estimate of the

relative importance of genetic differences (variation) among individuals in a populationregulating a phenotype distribution in apopulation.

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Heritability is calculated in different ways, but it always has the samemeaning: the proportion of phenotypic variation in a population thatis 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 ngerprint characters .

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Correlation in height between monozygotic twins (r = 0.84)Expected ?

Difference due to ?

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" P

2= "

G

2+ "

E

2


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Intelligence Quotient:

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 thatintelligence was the average of a number of distinct abilities (polygenic),that could be altered by teaching style and content (an environmentaleffect).

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Genetic Correlation in IQ Measurements IQ tests , score word use, number problems, memory processes, spatialconguration matrices and reaction times and are thought to measure

both cognitive abilities and a general inherited intelligence .

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h 2 =V

A

V E

+ (V A + V GxE + V D )

H 2 =V

G

(V G + V E )=

V G

(V P )

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There are genetic effects that are inherited in monozygotic twins,clones or inbred strains where there is no recombination, but are notinherited when sex recombines different genomes. In the numerator ofbroad sense heritability (H 2), V G includes dominance (V D) andgenotype/ environment interaction (V GE ) that can represent key sources

of phenotypic variation.

In sexual populations , additive genetic variation V A is the only inheritedsource of variation in the numerator of narrow sense heritability (h 2), therest is environmental interactions between alleles ( V D ) genes (epistasis)

or genes and their internal or external environments (V GE).

Broad sense heritability

Narrow sense heritability


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Different kinds of twin and other familial studies nd that IQ heritability estimatescenter on 0.75 (Nessier et al. 1996. American Psychologist 51: 77 - 101), although therange is from 0.4 to 0.9. This suggest that variation due to environmental differences(education) has less inuence 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 differencesbetween countries indicatehow the tests were

standardized.With 6 points per decadeover 10 decades..

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L21Biol261Qgenetics2014