Lecture 21 The genetic and environmental basis of complex traits Flashcards
Complex Traits
Mendel studied single-gene traits: each one was
determined by variation at a single gene and the traits
are for the most part not influenced by the environment
* However, complex traits are influenced by multiple
genes as well as by the environment
* Complex traits are much more prevalent than single
gene traits
Complex Traits
In many complex traits, the phenotype is determined
by a measurement: height in inches, milk by the gallon,
grain by the bushel, number of eggs, etc.
* Complex traits like these are called quantitative traits
because they are measured along a continuum with
only small intervals between similar individuals.
* By contrast, single-gene traits often appear in one of
two or a few different phenotypes, such as round vs.
wrinkled seeds.
Complex Traits
Human height
Milk production in dairy cows
Yield per acre of grain
Number of eggs laid by hens
More Complex Traits
Many common human diseases are also complex traits.
Many common human diseases are also complex traits.
High blood pressure
Obesity
Diabetes
Depression
complex traits.
Expression of complex traits is susceptible to lifestyle
choices and other environmental factors
* For example:
* Inadequate nutrition is linked to slow growth
* Salt intake is associated with an increased likelihood of high
blood pressure
* Environmental risk factor
* A junk-food diet high in fat and carbohydrates is a risk factor
for obesity and diabetes
* Adequate nutrition in farm animals is needed for normal
growth
* Adequate soil moisture and nutrients is needed for high yields
in crops
Complex Traits and Environmental
Influence
Environmental effects not only
affect the average phenotype
but variation in phenotype
from one individual to the next
* E.g. All the corn in a farmer’s
field is from the genetically
identical seed corn, but the
variation observed throughout a
field is due to the environment
(i.e., amount of sunlight, water,
wind, nutrients, etc.)
Complex Traits Influenced by Multiple
Genes
Polygenic Inheritance
* Complex, inherited characteristics controlled by
groups of several genes (= polygenes) at multiple loci
* When complex traits are affected by multiple genes,
the phenotype and genotype ratios observed by
Mendel are not observed.
* The number of genes affecting complex traits is
usually so large that different genotypes can have
very similar phenotypes, making it difficult to see the
effects of individual genes on a trait
Complex Traits Influenced by Multiple
Genes
One example is seed casing in wheat,
studied by Herman Nilsson-Ehle.
* Demonstrated that complex traits are
subject to the same laws that Mendel
worked out for single-gene traits, but that
the inheritance patterns are more difficult
to see because of the number of genes
involved.
* Three unlinked genes, each with two
alleles
* Bar graph approximates a bell-shaped
curve known as the normal distribution
* The phenotypes of many complex traits,
conform to a normal distribution.
Complex Traits Influenced by Multiple
Genes
Another example of polygenic
inheritance is skin color in
humans
* Controlled by at least three
independent genes (ABC)
* Each gene has two possible alleles
(dark and light) (A=dark; a=light
– AABBCC individual is very dark
– aabbcc individual is very light
– AaBbCc is intermediate
One Gene – Multiple Phenotypes
Important to remember that a gene does not code
directly for a trait
* A gene typically codes for a protein
* Genes can behave differently depending on how
their transcription is regulated
– Result: one gene does not always have one
phenotypic effect, it can have multiple effects
– One gene –> multiple phenotypic effects = pleiotropy
* Most genes, have multiple phenotypic effects
One Gene – Multiple Phenotypes
One Gene – Multiple Phenotypes
Examples of pleiotropic genes:
– Colouration pattern and crossed eyes of
Siamese cats
– These unrelated characters are caused by same
protein produced by same allele
– In humans, cystic fibrosis and sickle-cell disease
are pleiotropic (have multiple effects or
symptoms)
– In chickens, the frizzle gene not only causes
curly feathers but also high metabolism, blood
flow, body temperature, and digestive capacity,
as well as fewer eggs laid
Genotype-by-Environment Interactions
One feature of complex traits is
that genetics and environmental
effects can interact in ways that
are sometime unpredictable
* E.g. two strains of corn that were
introduced to different
nitrogen environments (graph)
* Strain 1 had little variation in its
yield in the higher nitrogen
environment
* Strain 2 increased its yield dramatically
* Each of the lines is known as the norm of reaction = how
environment affects phenotype across a range of environments
Genotype-by-Environment Interactions
Another example: flower colour in
Hydrangia
* Blue-violet flowers – in acidic soils
* White flowers – in neutral soils
* Rose-pink flowers - in alkaline soils
This type of interaction is important because it implies:
* that the effect of a genotype cannot be specified without
knowing the environment, and the other way around
* that there may be no genotype that is the “best” across a
broad range of environments, and likewise no environment is
“best” for all genotypes
*
Complex Traits in Health and Disease
Because many birth abnormalities and diseases (diabetes, high BP,
asthma, rhumatoid arthritis, scizophrenia, clinical depression etc.)
are complex traits, there is an interest in identifying the genes that
contribute to differences in risk factors
* Identifying these genes is major goal of current research in human
genetics
* Understand what the genes do prevent or treat disease
* Study of complex traits is beginning to show interesting patterns:
* Many genes contribute to condition
* Single genes have multiple effects (pleiotropy)
* Many of the genes are epistatic
* Many of the genes occur in clusters which reflects that they arose via
duplication and divergence, generating gene families
Complex Traits in Health and Disease
Another important observation is that the effects of the
genes on a trait are very unequal
* Some may have relatively large effects, while others have
small ones
* For the majority of genes that contribute to a complex
trait, the magnitude of their individual effects is typically
quite small
Personalized Medicine
The multiple genetic and environmental factors affecting
complex traits imply that different people can have the same
disease for different reasons
* A mutation in a particular gene
* Environmental factors
* Other genetic factors
* Traditional medicine is to use same medicine for same disease
* Personalized medicine treats the patient, not the disease
* Identify a patient’s genotype
* Match the treatment to the genetic risk factors of the patient
* Identify effective medicines
* Avoid harmful medicines
