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MCDB 1041 Class 33 Genes and Behavior Learning goals • Work with numbers to calculate concordance, heritability and relatedness when considering multifactorial traits. • Describe the basics of neurotransmission and its connection to behavior. • Interpret the possible effects of different mutations on behavior What are the genetic factors that contribute to a given behavior and how do they interact with the environment? First: need to figure out the relative fraction of a trait that is due to genetics This is called Heritability, and can be calculated by looking at: -relatedness -concordance 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 Heritability = concordance/ relatedness If you have a fraternal twin study in which the concordance is 20%, what is the heritability of the trait you are studying? a. 20% b. 40% c. 60% d. 10% What will happen if environment is more important than genetics? To figure this out, scientists 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 You think genetics is the primary contributor to the abuse of a new drug called “Rage”. You compare abusers of Rage to their monozygotic twins, dizygotic twins, siblings, adopted siblings, or siblings raised apart. Which of the following graphs matches your prediction that genetics plays the primary role in the abuse of Rage? B. concordance D. concordance (concordance = fraction of times that for each user, there was a sibling user in the category shown) concordance Adoptive siblings Siblings raised apart concordance Monozygotic twins Dizygotic twins Siblings C. A. Most behaviors involve the brain Drug addiction Thrill Seeking Behavior Eating Disorders Depression Bipolar disorder Schizophrenia Anxiety Attention Deficit Disorder (ADD) Attention deficit hyperactivity disorder (ADHD) Autism What genes could be important for behaviors? - genes that code for Neurotransmitter receptors - genes that code for proteins that affects how neurons connect to each other - lots of other possibilities! How does the brain work? • Neurons bring information to the brain and send information away from the brain (mostly to muscles) • Information is transmitted along AXONS to the SYNAPSE Transmitting neuron (Presynaptic neuron) Axon Receiving neuron (Postsynaptic neuron) Synapse Direction of action potential Neuron Animation: http://www.pbs.org/wnet/closetohome/animation/neuron-main.html Close-up of a Synapse Reuptake of the neurotransmitter dopamine After a neurotransmitter is released, it binds to receptors on the post-synaptic cell. This causes a change in that cell. Neurotransmitters are removed from synaptic cleft by: • enzymes that break them down • transporters that take the neurotransmitter back in to the presynaptic cell. This is called “re-uptake”. Once back in the presynaptic cell, they are broken down by enzymes and re-used. Which of the following would decrease the amount of neurotransmitter binding to its receptors? a. Higher production of neurotransmitters b. A non-functional reuptake protein c. A mutation that makes the enzyme that breaks down the neurotransmitter nonfunctional d. A mutation that makes the receptor nonfunctional Mood disorders When F.F discovered his wife in bed with another man, he shot and killed them both. F.F.’s defense ordered a psychiatric workup that included sequencing of two genes: • The gene that codes for the enzyme Monoamine oxidase A (MAO-A), which breaks down serotonin and dopamine • The gene that codes for the serotonin re-uptake transporter What were they trying to establish? Is this a valid approach for the defense? Depression: biochemical basis • Serotonin is known to affect mood, emotion, appetite and sleep. Usually, low levels of serotonin cause these disorders Clinical depressions can be treated with anti-depressant drugs like Prozac, Paxil or Zoloft. How might these work? A. break down serotonin B. decrease the uptake of serotonin into the postsynaptic neuron C. decrease the uptake of serotonin into the presynaptic neuron D. increase uptake of serotonin into the presynaptic neuron Antidepressants change the way the way serotonin is made available to neurons: – prevent serotonin from being broken down – prevent serotonin from being taken back up into neurons Both of these increase the level of serotonin, and thus (usually) improve mood Mood disorders are often triggered or exacerbated by environment—stress, life events Thus, scientists also look for genes that might impact response to stress as well Other mood disorders (bipolar, schizophrenia) are more challenging than treating clinical depression alone. Many genes have been associated with these disorders, but we still don’t understand enough! Interestingly, both bipolar disorder and schizophrenia have a higher H than depression Areas associated with bipolar disorder Although genetics alone may not explain mood disorders, we know that serotonin and dopamine levels effect mood AND how well people respond to drug therapy What’s the connection to genes? • Neurotransmitter receptors, re-uptake proteins and enzymes are coded for by genes in your DNA. • Neurotransmitters are themselves not coded for by genes, but the enzymes that help to synthesize them from precursors are • Alleles of these genes can affect how well these proteins work • These differences impact brain function (drug use or addiction, mood disorders, etc) and thus affect behavior