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MCDB 1041 Class 32
Studying disorders caused by
multiple genes and affected by
the environment
Learning goals:
•  Explain how multiple genes can be involved in one trait
•  Recognize the difference between characteristics of a
single gene trait polygenic trait, and multifactorial trait
•  Calculate how different allele combinations of multliple
genes impact one’s chance of getting a multifactorial
disease
Your environment (what you eat, what you do in your life,
how you are raised, etc) interacts with the genes you
inherit to impact your phenotype (and your behavior)
Phenotypes can be due to contribution of
genes or environment or both
Mendelian
phenotype due to a single gene
(example:cystic fibrosis)
Polygenic
phenotype due to multiple genes
(example: eye color)
Multifactorial
phenotype results from action of
genes AND the environment
(example: heart disease, mental illness)
Mendel’s pea plants: a trait (height)
was determined by two alleles, one
dominant, one recessive.
--thus, plants had two possible
phenotypes.
What would happen if multiple genes
all contributed to the height of a pea
plant, not just one gene?
Pea plants would have:
a.  an infinite number of different
possible heights
b.  multiple different possible
heights
c.  two heights (dwarf and tall)
Most human phenotypes
(especially behavior) are
polygenic or multifactorial
Eye color in humans: A polygenic trait?
Two genes, each with two possible alleles, can produce five different
phenotypes. If each gene encodes a protein that functions similarly,
what could determines the phenotype?
a.  Number of dominant alleles
b.  Interactions between the proteins coded by the genes involved
c.  Both a and b
Multifactorial traits
A trait controlled by multiple genes and by environment
is “multifactorial”. There are few true “polygenic
traits”. Most such traits are also impacted by
environment, making them even more difficult to
study.
Trait
Height
Skin color
Drug addiction
Heart disease
Blood pressure
environmental conditions
nutrition
sun exposure
exposure
diet
diet, stress
Height is influenced by genes and environment (nutrition)
during growth
Height shows a “continuous distribution”: there are people
in every possible category
men
women
When multiple genes AND the environment
are involved, there are many many small
variations in phenotype: this is called
continuous variation
Colon cancer ac*vity: suscep*bility to a disease when many genes are involved Making predic*ons about health What’s a SNP-­‐ChiP? A “chip” with LOTS of microscopic spots, each spot contains a short piece of single-­‐stranded DNA that matches a different gene. For example, let’s zoom in on two spots: Spot 1 = ATCATG (normal allele 1) Spot 2 = TTCATG (variant allele 2) Cut up DNA from person seeking test and aVach fluorescent tag to each piece. Heat DNA pieces to make single stranded and add to the chip. A HuGE Review iden*fies human gene*c varia*ons at specific places in the genome (called “loci,” which is plural for locus or loca*on) and describes: •  -­‐ what is known about the frequency of these varia*ons in different popula*ons, •  -­‐ iden*fies diseases that these varia*ons are associated with, summarizes the magnitude of risks, and evaluates associated gene*c tests. This informa*on (at some point) can be passed on to doctors and pa*ents for more info see: hVp://www.cdc.gov/genomics/hugenet/default.htm or hVp://www.hugenavigator.net/HuGENavigator/home.do When studying multifactorial traits, one needs to
take into account genetic relatedness
•  Relatedness is based purely on % of shared alleles between individuals
•  You can use relatedness to predict the chance two people have for
sharing a trait if the trait is due ONLY to genetics, not environment.
Percent shared
alleles
Relatedness
100%
1
50% (on average)
.5
50%
.5
Uncle/aunt and niece/nephew
25% (on average)
.25
Grandparent and grandchild
25% (on average)
.25
12.5% (on average)
.125
Relationship
Identical twins
Siblings
Parent and child
First cousins
Box Figure 7.01
What is the relatedness of
the two individuals shaded blue?
a. 1/2
b. 1/4
c. 1/8
d. 1/16
Concordance= % of pairs
of individuals that share a
particular trait
Example:
20 pairs of identical twins are being studied to look
at factors that influence heart disease
Of the 20 pairs, 10 sets of twins both have heart
disease.
The concordance in this example is 50%, or .5
Heritability
A measure of the % of phenotype due to genes
Estimated from the proportion of people sharing a trait
compared to the proportion predicted to share the trait.
Heritability = concordance/ relatedness
Concordance= % (or fraction) of pairs of related
individuals that share a trait
Relatedness= % (or fraction) of genetic relatedness (on
average) between people
Heritability for a
variety of traits
H=1
H=0
genes only
environment only
Let’s practice
how this
correlation is
calculated
Trait
Heritability
Clubfoot
0.8
Height
0.8
Blood pressure
0.6
Body mass
0.5
Verbal aptitude
0.7
Math aptitude
0.3
Spelling aptitude
0.5
Fingerprint ridge
count
0.9
Intelligence
0.5-0.8
Total serum
cholesterol
0.6
You have calculated the heritability of depression in a large
scale fraternal (non-identical) twin study to be 0.4.
Heritability = concordance/ relatedness
What is the concordance in your population of twins?
a. 0.2
b. 0.25
c. 0.4
d. 0.5
e. 0.8
What will happen if environment is more important than gene*cs? To figure this out, scien*sts compare phenotypes of: siblings raised together siblings raised apart Example: Tobacco addiction
What is most likely with tobacco addiction from this data?
a.  Genetics plays a strong role
b.  Genetics plays a minor role
c.  Genetics plays no role