The Inheritance of

Complex Traits
Chapter 5

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 “We used to think our fate is in the stars.
Now we know, in large measure, our fate is in our
genes.”
- James Watson

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 Lecture Objectives
 To distinguish between single gene diseases and
complex diseases

 To understand that interactions between our genome

and the environment make us what we are

 To provide several examples of multifactorial

traits/disorders

 To understand the Threshold Model, Heritability and

Concordance
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 Complex Traits
 Inherited traits and conditions caused by a combination
of genes and environment

 Polygenic trait controlled by 2 or more genes

 Multifactorial (complex) trait controlled by 2 or more

genes and environment
Multifactorial traits (complex traits) are:
polygenic
+
environmental component

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 Complex Traits and Variation in Phenotype
 Characteristics of complex traits
 Usually quantified by measurement, rather than
counting
 Two or more genes contribute to the phenotype;
however, the contribution from each individual
gene may be small
 Phenotypes vary across a wide range, and this
variation is best studied in populations, rather
than individuals
 Environmental factors interact with the genotype
to produce the phenotype

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Single
SingleGenetic
GeneticTraits
Traitsvs
vsComplex
ComplexTraits
Traits
Single-gene traits are discrete or qualitative
- Often produce an “all-or-none” effect

Polygenic traits produce a continuously varying phenotype

- Also called quantitative traits

Nature Reviews
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© Cengage Learning 2016
 Discontinuous and Continuous
Phenotypes
 Discontinuous variation
 Phenotypes that fall into two or more distinct,
nonoverlapping categories
 Example: pea plants are either dwarf or tall
 Continuous variation
 Phenotypes that are distributed from one extreme to
another in an overlapping – or continuous – fashion
 Example: human height varies from short to tall,
including many intermediate heights

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 Monogenic Disorders vs Complex Disorders

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Science, 2001
 Single Genetic Traits vs Complex Traits

Penetrance = the percent of individuals who have a certain

genotype and show the expected phenotype
Mendel traits penetrance = 100 %
Multifactorial
© Cengage LearningTraits
2016penetrance is less than 100%
Genes and the Environment Interact
 More than genomes affects traits and diseases

 Environmental factors include

◦ Prenatal environment
◦ What we eat, breathe
◦ Where we live
◦ Infections and more

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  More than genomes affects traits and diseases
 Environmental factors include
◦ Prenatal environment
◦ What we eat, breathe
◦ Where we live
◦ Infections and more
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© Cengage Learning 2016
Polygenic Traits
- A single characteristic can be influenced by multiple genes.
- Multiple genes have additive effects.
Individual genes follow Mendel’s laws, but their expression is hard
to predict
-Effect of genes is additive or synergistic
- However, input of genes is not necessarily identical
Bell curve
Most individuals are clustered
at ~average .Few individuals at
extremes of the phenotype

The distribution of phenotypic variation in a population for

a polygenic trait follows a bell-shaped (normal) curve
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 Complex Traits: e.g. Height
The difference in height between the two sets of
students is attributed to improved diet and better
overall health

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Complex Traits and Variation in
Phenotype (cont’d.)
 Example: Human skin color is controlled by 3 or
4 genes plus environmental factors, leading to a
wide range of phenotypes

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How Many Genes Control a Complex
Polygenic Trait?
 The greater the number of genes controlling a
trait, the greater the number of phenotypic
classes
 Example: human eye color

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 Skin Color is a Complex Trait

 Genetic contributions
 Phenotypic variations in human skin color are
determined by the amount, type, and distribution of
melanin
 The more recessive alleles, the lighter the skin
color; the more dominant alleles, the darker the
skin color
 Environmental contributions
 Skin color varies with latitude, but not longitude

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 Question
Heart disease, diabetes, cancer, alcoholism
and many mental illnesses can best be
described as:
(a) symptoms of a bad life-style
(b) infectious diseases caused by microorganisms
(c) multifactorial disorders with a possible
polygenic component
(d) all symptoms of Huntingdon’s disease
(e) monogenic disorders

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 Multifactorial Diseases
 Diabetes
 Hypertension and cardiovascular disease
 Behavioral traits
 Spina bifida
 Cleft Palate/Lip
 Club foot
 Cancer

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Complex (Multifactorial)
Diseases
- “Environmental” influences
act on a genetic predisposition
to produce a liability to a disease.

- Person affected if liability

above a threshold.

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Threshold Model
 Individuals must have a certain number of genes and
exposure to develop the phenotype

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Genetic Liability
 Number of alleles in genotype for a specific trait

 Measured by examining # of affected relatives

 Genetic predisposition must be exposed to

environmental agent

 Factors used to predict risk

◦ Consanguinity
◦ Number of affected children
◦ Severity of disorder
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Behavior, Genes, and Environment
 5-HTT gene controls nerve impulses in the brain

 Variation can cause changes

in stress-response behavior

 Two alleles:
one long and one short

 Study showed increased risk

of depression for those with
two copies of short allele

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 Heritability
measures the genetic contribution to
phenotypic variation
The proportion of phenotypic variation that is
caused by different genotypes is called the
heritability

Based on known levels of genetic relatedness

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Why twin studies are important in genetics?

• The greater similarity of MZ twins than DZ twins

is considered evidence of genetic factors

How to calculate the relative influence of

genetic vs. environmental factors on
multifactorial traits?

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 Twin Studies and Multifactorial Traits
 Twin studies are used to separate and evaluate the
genetic and environmental factors responsible for
phenotypic variation
 Identical twins separated at birth
 Identical genotype, different environments

 Adopted children living in same family

 Different genotypes, same environment

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The Biology of Twins: Monozygotic
 Monozygotic (MZ) twins
 Genetically identical twins derived from a single
fertilization event involving one egg and one
sperm

Monozygotic (MZ)
twins

Single fertilization
event

Mitosis

Two genetically
identical embryos
(a)
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Monozygotic (identical) Twins Share a
Single Genotype

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The Biology of Twins: Dizygotic

 Dizygotic (DZ)
 Twins derived from two separate and nearly
simultaneous fertilizations, each involving one
egg and one sperm
 DZ twins share about 50% of their genes
Dizygotic
(DZ) twins

Two
independent
fertilization
Mitosis events

Two embryos
(b) sharing about
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Twins and Concordance

 A trait is concordant if both members

of a twin pair have the trait
 A trait is discordant if only one
member of a twin pair has the trait

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Concordance
measures the frequency of expression of a trait in both
members of monozygotic (MZ) or dizygotic (DZ) twins

Twins show
concordance if both
have a trait and are
discordant if one twin
has the trait

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Figure 3.16 Concordance rates for identical and fraternal twins for several behavioral dimensions. FROM PLOMIN ET AL., 1994.
Table 5.2 Concordance Values in MZ and
DZ Twins for Some Complex Traits

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 Environmental effects:
identical twins are not identical.

Stacey Warren after her gastric bypass

surgery with her identical twin Kelly

When they were 25, for identical twins

Gwennan and Elin Thomas a shocking
event would mark the sisters apart when
one developed alopecia, which causes
hair loss Learning 2016
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