Lesson 14: Heritability Before you begin!
Homework Name
o Your ideas: Be prepared to share with your peers
 Is alcoholism genetically controlled?

How do you study twins to learn about inheritance of traits that are also environmentally
influenced?
o Compare identical and fraternal rates of shared phenotypes
o Compare twins reared together to those raised apart for rates of shared phenotypes
o Both comparisons help
o Twins don’t offer us any particular insights about these traits
 How related are fraternal twins?

o Previously learned material
 What are three types of proteins that influence brain function and brain chemistry?
Choose 3.
Phospholipids
Receptors
Nucleic acids
Transporters
Enzymes
Vitamins
Glucose
 Why do we care about CYP3A4?

What neurochemical is important in the Reward Pathway?
Serotonin
Endorphin
GABA
Dopamine
Heroin
Required Reading Liska
Review: Sections 4.5 on Metabolism of Drugs, 4.6 on How People Can Respond Differently to
Drugs, and 9.9 on Theories of Alcoholism: What Is an Alcoholic”
Internet
 http://science.howstuffworks.com/environmental/life/genetic/twin1.htm Read about the “Jim”
twins.
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http://en.wikipedia.org/wiki/Concordance_%28genetics%29 Read about measurements in twin
studies.
http://learn.genetics.utah.edu/content/addiction/candidate/ Read about identifying specific
genes related to addiction-Activity 7
http://learn.genetics.utah.edu/content/addiction/genes/ Read about discovering the genetic
underpinnings of addiction.
http://learn.genetics.utah.edu/content/pharma/ Read about “designer” drugs – drugs targeting
specific individuals more than others-Activity 9
Supplemental Reading
Internet
 http://science.howstuffworks.com/environmental/life/genetic/twin2.htm (basics on twinning)
 At http://learn.genetics.utah.edu/content/pharma/ feel free to peruse other links, in particular
the one about “Issues” related to pharmacogenetics.
 For a mathematical approach to heritability see: http://en.wikipedia.org/wiki/Heritability
Guiding Questions
1. What do model organisms have to offer us as we study complex behavioral traits?
2. If genes control a trait, in part, what can you expect for twins?
3. What types of genes might influence drug taking and how are specific genes determined to be
(or not to be) influential in a trait?
4. What types of genes influence addiction to alcohol, or addiction generally.
5. What is pharmacogenetics and how might this field of study influence the drugs you will be
prescribed in 10 years time?
Key Terms
 Identical and fraternal twins
 Concordant vs. discordant
 Reward Deficiency Syndrome
 Pharmacogenetics
Need to pick this up-Lesson 12 Activity Eight: Pedigree Analysis
While Punnett squares are useful for solving problems with organisms that have large numbers of offspring,
human pairs often have small enough families that proportions are not particularly handy to solve the
inheritance pattern of a trait. Often a geneticist will examine MANY families to determine how a trait is
inherited. Each family’s information is summarized in this kind of a study by making a “family tree” or a
pedigree. Pedigrees are diagrams that show familial relationships in a standard (and therefore easy to
interpret by others) way and represents the phenotype of each individual in the family.
Conventions used to make and solve pedigrees:

Circles represent women and girls

Squares represent men and boys

Filled symbols represent people with “the trait” (a disease or a phenotype of interest).

Empty symbols represent people who do NOT have “the trait”

If the trait shows incomplete dominance, the symbols will be hatched or have a dot in the middle

Matings are connected by a line between a male and a female

Offspring from a mating arise from a stem below that line, and are given in order of birth from a “sib
line”

Twins descend from the sib line as a pair, either directly from the sib line (fraternal twins) or from a
stem off the sib line that then forks (identical twins)
Visit the interactive pedigree-making site at http://learn.genetics.utah.edu/content/addiction/genetics/pi.html
Activity One: History Side Bar
At http://science.howstuffworks.com/environmental/life/genetic/twin1.htm : read about the identical twins,
separated at birth, and both named “Jim”.
Activity Seven: Candidate Gene Approach Homework to prepare for discussion
Work through the activities found at : http://learn.genetics.utah.edu/content/addiction/candidate/ Some
of this is new material (we haven’t talked about nicotine yet but soon will), but in the section “Where do We
Begin” – it does suggest one way, different from the story of Dr. Heberlein, that researchers look for particular
genes that might be good candidates for ones influencing drug use. Some of this material is also review. Pay
particular attention to the 5 slides in the section “How Genes Affect Behavior”. Be able to answer the question
How is the protein encoded by allele 1 different from the proteins encoded by alleles 2 and 3?
Try to come up with a molecular answer and a functional answer.
Activity Eight: Reward Deficiency Syndrome: More detail
The dopamine receptor gene mentioned in activity six is also implicated in the addictions to numerous
substances and even addictive behaviors. For each neurotransmitter, there are several known receptors. The
dopamine receptor 2 (D2DR or DRD2) is strongly implicated in addictions.
Read the abstract by Blum K, Braverman ER, Holder JM, Lubar JF, Monastra VJ, Miller D, Lubar JO, Chen TJ,
Comings DE, Found in 2000 J. Psychoactive Drugs
Some terms you might be unfamiliar with
Mesolimbic – the area around the limbic system – in particular the nucleus accumbens
Enkephalin – an endogenous opiate, like endorphin
Substantia niagra – an area of the brain that utilizes dopamine and controls movement
Pleiotropic – many causes, both genetic and otherwise
The dopaminergic system, and in particular the dopamine D2 receptor, has been implicated in reward
mechanisms. The net effect of neurotransmitter interaction at the mesolimbic brain region induces
"reward" when dopamine (DA) is released from the neuron at the nucleus accumbens and interacts
with a dopamine D2 receptor. "The reward cascade" involves the release of serotonin, which in turn at
the hypothalmus stimulates enkephalin, which in turn inhibits GABA at the substania nigra, which in
turn fine tunes the amount of DA released at the nucleus accumbens or "reward site." It is well known
that under normal conditions in the reward site DA works to maintain our normal drives. In fact, DA
has become to be known as the "pleasure molecule" and/or the "antistress molecule." When DA is
released into the synapse, it stimulates a number a DA receptors (D1-D5) which results in increased
feelings of well-being and stress reduction. A consensus of the literature suggests that when there is a
dysfunction in the brain reward cascade, which could be caused by certain genetic variants (polygenic),
especially in the DA system causing a hypodopaminergic trait, the brain of that person requires a DA fix
to feel good. This trait leads to multiple drug-seeking behavior. This is so because alcohol, cocaine,
heroin, marijuana, nicotine, and glucose all cause activation and neuronal release of brain DA, which
could heal the abnormal cravings. Certainly after ten years of study we could say with confidence that
carriers of the DAD2 receptor A1 allele have compromised D2 receptors. Therefore lack of D2
receptors causes individuals to have a high risk for multiple addictive, impulsive and compulsive
behavioral propensities, such as severe alcoholism, cocaine, heroin, marijuana and nicotine use,
glucose bingeing, pathological gambling, sex addiction, ADHD, Tourette's Syndrome, autism, chronic
violence, posttraumatic stress disorder, schizoid/avoidant cluster, conduct disorder and antisocial
behavior. In order to explain the breakdown of the reward cascade due to both multiple genes and
environmental stimuli (pleiotropism) and resultant aberrant behaviors, Blum united this
hypodopaminergic trait under the rubric of a reward deficiency syndrome.
Reward deficiency syndrome thus is a state of mind that causes people to seek “more extreme”
ways to satisfy the demands of their reward pathway.
Activity Nine: Pharmacogenetics
Start by visiting http://learn.genetics.utah.edu/content/pharma/. Select the link “Your Doctor’s New
Genetic Tools”. Work through this animation, using the following guiding questions as you read:

What is pharmacogenetics? Why might it be beneficial – how will it change medicine?

What is Purinethol?

Why is it not an ideal chemotherapy for leukemia patients?

What is the TPMT enzyme and how does it relate to leukemia patients and Purinethol?

What did the doctor discover about Latrice and how did this influence the medication he
recommended?
In Lecture: Record responses to discussion
questions
How would you study the role of genes? How would you determine if a trait was inherited?
What is the difference between concordant and discordant in twins?
Can one have an addictive personality?
What type of genes should we consider when talking about drugs?
Even with all this genetic info, does this mean one WILL be an alcoholic?