Quantitative Genetics

Polygenic traits
1. Controlled by several to many genes
2. Continuous variation—more variation not as easily characterized into
classes; individuals fall into a range of phenotypes. (Think about height)
3. Genes have an additive effect on phenotype
4. Are studied in populations
Multifactorial or 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
1
Complete elimination of environmental variation is impossible
Some quantitative phenotypic traits that evolved along the human lineage, or in
some populations

(1) Large brain size

(2) Light skin color
(3) Altriciality at birth
(4) Longer juvenile period
(5) Smaller teeth
(6) Relative hairlessness
(7) Increased susceptibility to cancer, heart disease
(8) Language skills, technical skills
 The Basis of Additive Inheritance
1. Characteristics can be quantified (measured, counted, weighed,
etc.)
2. Two or more genes, at different places in the genome, influence
the phenotype in an additive way (polygenic).
3. Each locus may be occupied by an additive allele that does
contribute to the phenotype, or a non-additive allele, which does
not contribute.
4. The total effect of each allele on the phenotype, while small, is
roughly equal to the effects of other additive alleles at other gene
sites.
5. Together, the genes controlling a single character produce
substantial variation in phenotype.
6. Analysis of polygenic traits requires the study of large numbers of
progeny from a population of organisms.
An example: wheat grain color.
Cross true-breeding plants with white berries to true-breeding plants with dark red grains.
The resultingF1 all exhibit an intermediate color. When the F1s are crossed, the result is a range of color.
Wheat Grain Color

True-breeding plants with

white vs. red berries were
crossed to create an F1of
intermediate color, then
the F1 plants were crossed
to produce the range of
colors.
The curve is called a normal
distribution, with the
largest number of
individuals in the
intermediate range, with
fewer at each extreme.
 A loose distinction
“Qualitative” traits:
• Blood groups (ABO)
• Coat color in cats
• Color vision
Difference between
phenotypes of two individuals
can be explained by difference
in genotype at a small number
of loci (for example, 1 or 2).
Mendelian ratios in F1
Quantitative traits:
• Height
• Weight
• Facial features
The phenotype is determined
– to some extent – by
genotype, but phenotypic
difference between individuals
is due to difference in
genotype at a large number of
loci.
No Mendelian ratios in F1
5
In a population, phenotypes of individuals
for a quantitative trait tend to be normally
distributed

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 Central limit theorem
Carl Friedrich Gauss 

If a variable is the sum of many independent

variables, then its distribution will be normal:

x 2
e 7
In this example, a trait (color)
is controlled by three loci, A,
B, and C, each of which
occurs in only 2 alleles.
The actions of the alleles is
somewhat additive, in other
words, an aabbcc organism is
all white, whereas an AABBCC
organism is dark red.
The remarkable thing is, even
with such a simple system
(three loci with two alleles
each!), we can get a
remarkably “smooth”
distribution of phenotypes!
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 Polygenic Inheritance
When individual plants from the F2 are selected and mated, the phenotype of
the resulting offspring also produces a range of phenotypes and a similarly
shaped curve:
There is a range of phenotypes, but most of the offspring are similar in color to
the parents.

Determining the Number of Genes—the 1/4n Rule

The number of genes may be calculated if
--the proportion of F2 individuals expressing either of the two most extreme (i.e.
parental) phenotypes can be determined according to the following formula:
1/4n=proportion of offspring either red or white
1 = 1; solve for n, 43=64
4n 64

Determining the Number of Genes—the (2n + 1) Rule

If n = the number of gene pairs, then (2n + 1) will determine the total number of categories of
phenotypes.
In our example, there were 7 phenotype classes:
(2n + 1) = 7
(7-1) = 6 = 3
2 2
 Genotype Plus Environment
Note that genotype (fixed at fertilization) establishes the
range in which a phenotype may fall, but environment
influences how much genetic potential will be realized.

(So far, we have assumed no influence of environment on

the cross examples used)

Significance of Polygenic Control

Most traits in animal breeding and agriculture are under
polygenic control:
Height, weight, stature, muscle composition, milk and egg
production, speed, etc.
 Biometry
Biometry is the quantitative study of biology and
utilizes statistical inference to analyze traits
exhibiting continuous variation.

While the observations of an experiment are hoped

to represent the population at large, there may be
random influences affecting samples that adds to
variation in the study population. Statistical
analysis allows researchers to predict the sources
of variation and the relative influence of each
source.
 Purpose of Statistical Analysis
1. Data can be analyzed mathematically and reduced to a summary
description.
2. Data from a small but representative and random sample can be
used to infer information about groups larger than the study
population (statistical inference).
3. Two or more sets of experimental data can be compared to
determine if they represent different populations of
measurements.

Statistical analysis is all about defining the sources of

variation.
Ultimately, we want to be able to assign proportions
of the variation to their different sources, to sort out
that variation due to our treatment or design.
 Statistical Terms

Mean:
The distribution of two sets
of phenotypic
measurements cluster
around a central value.
The mean is the arithmetic
average of the set of
measurements, the sum
of all of the individuals
divided by the number of
individuals.
 Mean
The mean is arithmetically calculated as
Mean = Xi/n
Where Xi is the sum of all the individual values
and n is the number of individual values
Observed values for eight samples
{2,2,4,5,5,6,6,8}
Xi is 38
37/8 = 4.75
Therefore, the mean for this sample is 4.75

Median
If the data are arranged from smallest to largest value, the median value is the
central number.
{2,2,4,5,5,6,6,7,8}
So the median value for this data set is 5.
 Range
Range is the distance between the smallest value in a set and the largest value in a
set.
{2,2,4,4,5,6,6,7,8}
The range for this set is 2 to 8.

Frequency Distribution
Median and range give information about the frequency distribution, or shape of the curve.
The values of two different data sets may have the same mean, but be distributed around that
mean differently.

Variance
Variance is a value that describes the degree to which the values in a data set diverge from the
mean.
The variance within the data set is used to make inferences or estimate the variation in the
population as a whole.

Calculate Variance (s2)

s2 = (Xi-mean)2 /n – 1
 Standard Deviation
Because variance is a squared value (s2) its unit of
measurement is also squared (inches, feet, kg, etc.)
To express variation in the original units, simply take the
square root of the variance, or standard deviation.
s =  s2
Standard Error of the Mean
To estimate how much the means of other similar samples from the same population
might vary, we calculate the standard error of the mean.
The SE is a measure of variation of sample means in repetitions of an experiment, or
more simply, a measure of accuracy of the sample mean.
SE is the standard deviation, divided by the square root of the number of individuals.

SE = s/n
Because SE is divided by the square root of n, the value will always be smaller than the standard
deviation.
Crisper distinction between Mendelian and quantitative traits:
For a quantitative trait, the range of phenotypes exhibited by individuals
in any given genotypic class is BROADER than the difference between
two average individuals of two different genotypes. In contrast, for a
Mendelian trait, two individuals of the same genotype will tend to be
relatively similar, and all quite strikingly distinct from individuals of a
different genotypic class.

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Continuous traits
= ratio of genotypic variance to phenotypic variance
Heritability is an estimate of
how much variability in a
population is due to genetic
factors, separate from
environmental factors.

In genetics, statistics are all

about determining the relative
impacts of heredity vs
environment on phenotypic
variation.
Experiments test the source or origin of variation.
One way to assess genetic influence is to use inbred or genetically similar groups of
animals or plants, and rear them under a range of environmental conditions.
Variation between different strains reared under similar conditions can be assigned to
genetic differences.
Variation among members of the same strain reared under different conditions can be
assigned to non-genetic influences, called “environmental” effects.
Heritability (H2)
H2 is an analysis of variance among individuals of a known genetic relationship.
H2 measures the degree to which phenotypic variance (VP) is due to genetic factors with the
following limitations
1. For a single population
2. Under the limits of environmental variation during the study
The heritability does not determine the proportion of the total phenotype due to genetic
factors.
The heritability does estimate the proportion of observed variation in the phenotype due to
genetic factors in comparison to environmental factors.
The heritability is not absolute for any given character, but measured in different populations
under different degrees of environmental variation.

Therefore, it’s most useful in inbred or genetically similar strains.

Also, it’s not particularly useful in determining the selection potential of quantitative traits, since
it takes into account all sources of genetic variation, not just specific additive genetic effects.
According to Falconer,

Degree of genetic resemblance

Degree of genetic determination

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Language you speak
Traits resulting from physical damage- injuries etc
Religion you follow

Dimples
Mass of the brain
Myopia
Hip dysplasia in dogs
A quantitative trait locus (QTL) is a locus (section of DNA) which
correlates with variation of a quantitative trait in the phenotype of
a population of organisms.
QTLs are mapped by identifying which molecular markers (such
as SNPs or AFLPs) correlate with an observed trait.
This is often an early step in identifying and sequencing the
actual genes that cause the trait variation.

The term QTL was first coined by Gelderman in 1975

William Ernest Castle and his student Sewall Wright
have contributed a great deal to the development of
this field
Polygenic inheritance , strictly speaking, refers to inheritance of
a phenotypic characteristic (trait) that is attributable to two or
more genes and can be measured quantitatively. Multifactorial
inheritance refers to polygenic inheritance that also includes
interactions with the environment.
quantitative trait locus (QTL)
QTLs are often found on different chromosomes.

The number of QTLs which explain variation in the phenotypic trait

indicates the genetic architecture of a trait. It may indicate that plant
height is controlled by many genes of small effect, or by a few genes of
large effect.

Typically, QTLs underlie continuous traits .

Moreover, a single phenotypic trait is usually determined by many

genes. Consequently, many QTLs are associated with a single trait.

Another use of QTLs is to identify candidate genes underlying a trait.

Once a region of DNA is identified as contributing to a phenotype, it can
be sequenced. The DNA sequence of any genes in this region can then
be compared to a database of DNA for genes whose function is already
A doubled haploid (DH) is a genotype
formed when haploid cells undergo
chromosome doubling. ... Haploid cells
are produced from pollen or egg cells
or from other cells of the gametophyte,
then by induced or spontaneous
chromosome doubling, a doubled
haploid cell is produced, which can be
grown into a pure
homozygous doubled haploid plant
Near-isogenic lines (NILs) are
strains whose genetic make
ups are identical except for
few specific locations or
genetic loci
 QTL mapping
Mapping by linkage:
Take pedigrees with same frequency of
individuals affected by a trait (e.g.,
schizophrenia), and scan their entire genome
for “linkage” with some polymorphic marker
(e.g., a RFLP).

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Mapping a qualitative trait by linkage

65
11.24

66
 Analysis of a quant trait: Tomato fruit
P1 ave=6oz P2 ave=18oz

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

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

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

=1.29 =4.27

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

=1.13 =2.06
 68
Brockmann and Bevova (2002). Trends Genet. 18: 367.
69
“The fact that single genes
can be modified and
produce obese mice
conclusively shows that
genes contribute to
obesity. However, the
effect of a tested gene –
especially if it contributes
to complex traits –
depends on the genetic
background (i.e., the
effects of other genes –
and thus might or might
not produce the expected
phenotype, or a milder
phenotype.”

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Brockmann and Bevova (2002). Trends Genet. 18: 367.
For “simple” traits, the genotype-phenotype
relationship is fairly unambigious, issues of
penetrance and expressivity aside. If you are
homozygous for HbS, you will get SCA, no
question about it. It is largely irrelevant, what
environment you grow up in – you’ll get
anemia (although medical care will help you
lead a better life, no question about that).
For qualitative traits, the relationship
between genotype and phenotype is
impossible to express in a simple statement,
so the general public, eager for simple
solutions that fit its short attention span, has
become enamored of the word “tendency.”
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Y-DNA Haplogroup Geographic Locations
Haplogroup A is found mainly in Southern Africa and represents the oldest Y-chromosome
haplogroup. It is believed to be the haplogroup of Y-chromosomal Adam.
Haplogroup E1b1a is predominantly found among sub-Sahara African populations.
Haplogroup E1b1b is predominantly found around the coast of the Mediterranean.
Haplogroup G has an overall low frequency in most populations and is found widely distributed
in Europe, northern and western Asia, northern Africa, the Middle East and India.
Haplogroup J and its subgroups are predominantly found around the coast of the
Mediterranean and the Middle East. Subgroups are frequently associated with Jewish
populations.
Haplogroup I and its subgroups are predominantly found in northwestern Europe (Scandinavia)
and central Europe. One subgroup is considered to be Viking.
Haplogroup N is predominantly found in northeastern Europe and especially in Finland.
Haplogroup Q is primarily associated with Native American populations.
Haplogroup R1a and its subgroups are predominantly found in eastern Europe and in western
and central India and Asia. In eastern Europe, it is frequently associated with Slavic populations.
Haplogroup R1b and its subgroups are predominantly found in western Europe and the British
Isles. It is the most common haplogroup in Europe and a subgroup of R1b is believed by some
researchers to be Celtic.
 it is highest in Central Asia and lowest among
the indigenous peoples of the Americas and
Australia. However, there are relatively high
frequency pockets in Africa as well. Overall in
the world, B is the rarest ABO blood allele. Only
16% of humanity have it.
The A blood allele is somewhat more common around
the world than B. About 21% of all people share
the A allele. The highest frequencies of A are found in
small, unrelated populations, especially the Blackfoot
Indians of Montana (30-35%), the Australian
Aborigines (many groups are 40-53%), and the Lapps,
or Saami people, of Northern Scandinavia (50-
90%). The A allele apparently was absent among
Central and South American Indians.

The O blood type (usually resulting from the absence of

both A and B alleles) is very common around the world. About 63% of
humans share it. Type O is particularly high in frequency among the
indigenous populations of Central and South America, where it
approaches 100%. It also is relatively high among Australian Aborigines
and in Western Europe (especially in populations with Celtic
ancestors). The lowest frequency of O is found in Eastern Europe and
Central Asia, where B is common.
 77
Achillea millefollium (yarrow)
Take 7 yarrow plants,
grow cuttings from
each one at different
elevations.

Measure each “child”

at each elevation.

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79
 Risk of breast cancer and physical exercise in BRCA1/2
mutation carriers: an example of how the norm of reaction
illuminates the modification of a “genetic tendency” by
environment

“Physical exercise and lack of

obesity in adolescence were
associated with significantly
delayed breast cancer onset.”

M.-C. King et al. Science 2003 80

 The reality of “Nature vs. nurture”: a group of individual of identical genotype, when
placed in a normally distributed range of environments (X axis) will yield a population
with a normally distributed range of phenotypes (Y axis), but the shape of the distribution
will be a function BOTH of that genotype’s norm of reaction and of the distribution of
environments.
1. Each organism is the subject of
continuous development
throughout its life. The
environment’s effects on the
organism will vary depending
on when in development the
effect is exerted (e.g., PKU).
2. The developing organism is not
under the effect of genes and
the environment acting
separately. It is under the effect
of mutually interacting genes
and the environment. In the
resulting organism, the effects
of nature and nurture are as
“separable” as effects of flour
and of the oven in the baked
muffin. 81
 And therefore …
For any given individual, assigning percentages to “genes” and
“environment” in determining the phenotype for a given
quantitative trait has no meaning.
For each given quantitative trait, each human being (a specific,
given genotype), has a norm of reaction. The “norm of reaction”
describes exactly how the trait will develop when very many
individuals of exactly identical genotype will be placed in many
different, very carefully controlled environments. Careful analysis
of the norm of reaction may, perhaps, tell us a little bit about
how the genes responsible for that quantitative trait interact
with the environment in that trait’s development. No percentage
values will be assigned to “nature or nurture” at any point in
time—they are meaningless in this context.

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