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Genetics of Behavior (Learning Objectives)

• Recognize that behavior is multi-factorial with genetic components• Understand how multi-factorial traits are studied. Explain the terms:

incidence, prevalence, empiric risk, heritability, genome-wide association studies

• Explain the structure of neurons and the process of neurotransmission in the brain that affects behavior, perception, and mood.

• Recognize common behavioral disorders in the US population and their manifestation as a continuum of multi-factorial nature traits.

• Explain the different types of eating disorders.• Explain the importance of sleep, its stages, and sleep disorders.• Recognize intelligence as a complex multi-factorial trait and limitations of the

IQ test.• Explain drug the biological basis of drug addiction and drug abuse. • Explain the different types of mood disorders and neurological basis,

including treatment.• Explain schizophrenia • Explain the spectrum of disorders of autism and its underlying neurological

basis

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Genetics of Behavior (Outline)

• Behavior is multi-factorial with genetic components• Studying multi-factorial traits: incidence, prevalence, empiric risk, heritability,

genome-wide association studies • Neuron structure and brain neurotransmission (behavior, perception, and

mood).• Common behavioral disorders in the US; manifestation as a continuum of

multi-factorial traits. • Eating disorders.• Sleep, its stages, and sleep disorders.• Intelligence and IQ test and its limitations. • Drug addiction and drug abuse. • Mood disorders and neurological basis, including treatment.• Schizophrenia • Autism spectrum

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Genes and BehaviorBehavior is a complex continuum of emotions,

moods, intelligence, and personality

Behavior occurs in response to environmental factors, but how we respond has genetic underpinnings, multi-factorial in nature

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Investigating Multi-factorial Traits

Population StudiesIncidence is the number of new cases of a

disorder diagnosed in a population within a specific time

Prevalence is the proportion or number of individuals who have a particular trait within a specific time

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Statistical Measures for studies of multi-factorial traits

Variations in traits due to involvement of more than one gene and other environmental influences

1. Empiric risk (single traits)2. Heritability (polygenic traits)

- Coefficients of Relatedness

- Twin Studies

3. Adopted Individuals 4. Genome-wide associations (most recent)

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Empiric Risk- A statistical measure of the likelihood that a trait will

recur based on incidence (observation)- Cleft lip is more likely in a person who has a relative

with the condition

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Heritability (H)Heritability describes the population, not individuals Measures the fraction of phenotypic variance in a population that can be attributed to contributions of additive, dominant, and epistatic (multi-genic interactions), as well as maternal and paternal effects

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Heritability (H)Proportion of phenotypic variability within a

population that is due to genetic components over a specific period

Heritability is estimated using alternative statistical methods

- Comparing the proportion of people sharing a trait to the proportion predicted to share the trait if it was inherited in a Medenlian fashion.

- Derived by knowing the blood relationships of the individuals (coefficient of relatedness)

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Heritability (H)

Comparing actual proportion with the predicted one

H “can range from 0 (no genetic contribution) to 1 (all differences on a trait reflect genetic variation)”

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Coefficients of Relatedness

- Used to calculate heritability

- The proportion of genes shared between two people related in a certain way

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Separating Genetic and Environmental Influences

Dizygotic twins = Shared environment and 50% of genes

Monozygotic twins = Identical genotype and shared environment

Twins raised apart = Shared genotype but not environment

Adopted individuals = Shared environment but not genes

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Twin StudiesConcordance measures the frequency of expression

of a trait in both members of monozygotic (MZ) or dizygotic (DZ) twins

- Twins who differ in a trait are said to be discordant for it

For a trait largely determined by genes, concordance is higher for MZ than DZ twins

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Twins

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Adopted Individuals• Similarities between adopted people and

adopted parents reflect mostly environmental influences

• Similarities between adoptees and their biological parents reflect mostly genetic influences

• Therefore, information on both sets of parents can reveal how heredity and the environment both contribute to a trait

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From Genetic to Genomic Studies

• Genetic Studies:- Searching for genes and Gene mapping

- Linkage studies using recombination frequencies- Haplotype studies: set of genes inherited together

from one parent (haploid) located in the same region- Used family pedigrees

• Genomic Studies- Several techniques led to genome-wide

associations for correlation between patterns of genomic variations and phenotypes in large groups of individuals

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Genomic Variation Studies

• Single Nucleotide Polymorphisms (SNP)

• Copy number variants of tandem repeats (CDVs)

• Gene Expression patterns: correlation of conditions to under or over expression of an array of genes

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SNPs

• DNA base variant in at least 1% of the population (polymorphic)

• Span the genome not related to a particular gene

• http://biology-animations.blogspot.com/2008/02/snp-animation.html

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HapMaP Project

https://www.genome.gov/pages/education/dnaday/teachingtools/makingsnpsmakesense.html

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Genome-wide association studies seek genomic variations that are shared with much greater frequency among individuals with the same trait than among others

Microarray Technologyhttp://highered.mcgraw-

hill.com/olcweb/cgi/pluginpop.cgi?it=swf::535::535::/sites/dl/free/0072437316/120078/micro50.swf::Microarray

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Limitations of Genome-Wide Association Studies

• Include so many data points and so are prone to error

• Reveal associations between two types of information, not causes

• Bias can be introduced in the way the patient population is selected

• Accuracy is affected by complicating factors, such as phenocopy and epistasis

• May miss extremely rare SNPs

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Behavioral Genetics

Considers nervous system function and variation, including mood and mind

Uses studies of - Empiric risk- Twin studies - Adoption studies- Association studies with SNPs and - Analysis of specific mutations that are present in

individuals with the behavior

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The Human BrainBrain weighs about 3 pounds

- Consists of 100 billion neurons and at least a trillion other supportive and nurturing cells called neuroglia

Neurons communicate across synapses using neurotransmitters

Genes control the production and distribution of these chemical signals

The Brainhttps://www.youtube.com/watch?v=kMKc8nfPATI (14 mins)(Bozeman Science)

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Neurotransmission- Within a single neuronElectric signalhttps://www.youtube.com/watch?v=5V7RZwDpmXE

https://www.youtube.com/watch?v=qPix_X-9t7E

- Between two neuronsChemical signalhttps://www.youtube.com/watch?v=p5zFgT4aofA

Figure 8.1

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https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2673233/figure/F1/

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Behavioral Genetics

Genetic studies of behavioral disorders are challenging traditional psychiatric classification

- These disorders may lie on a continuum with many genes having input

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Common Disorders of Behavior

• Eating • Sleep• Intelligence (?)• Drug Addiction• Mood • Schizophrenia• Autism

Neurodegenerative disease: Parkinson’s role of appendix (alpha-Synuclein)

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Eating DisordersIn the US, 5-10 million people have eating disorders.

About 10% are male

Twin studies reveal a heritability ranging from 0.5-0.8

Genes whose products control appetite or regulate certain neurotransmitters may predispose to eating disorders

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Eating DisordersAnorexia nervosa – Psychological perception of obesity

and intentional starvation

Bulimia – Psychological perception of obesity and intentional vomiting

Muscle dysmorphia – Psychological perception of being too small

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https://examinedexistence.com/5-different-brainwave-frequencies-mean/

• Brain waves measure the frequency of the electric activity• Frequency measured is Hertz (Hz) • the lower the frequency the less activity

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SleepWithout sleep animals dieStages of sleephttp://www.youtube.com/watch?v=qEWbu37fH9k ( >1 min)http://www.youtube.com/watch?v=uWYwMnMMEoU&NR=1Twin studies indicate 4 of the 5 stages of sleep have a hereditary

component- The fifth stage, REM sleep, is associated with dreaming and so reflects input of experience more than genes

http://www.ninds.nih.gov/disorders/brain_basics/understanding_sleep.htm

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https://commons.wikimedia.org/w/index.php?title=File%3AVideo_schematic_of_glymphatic_flow.ogv

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Narcolepsy with CataplexyDaytime sleepiness with tendency to rapidly fall

asleep (narcolepsy) and periods of muscle weakness (cataplexy).

The genetic basis was first identified in dogs, then humans

http://www.youtube.com/watch?v=l2x14qETS7E

Figure 8.3

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Narcolepsy is a sleep disorder that affects approximately 1 in 2,000 individuals. It is characterized by irresistible excessive daytime sleepiness as well as cataplexy, the sudden loss of muscle tone in response to strong emotions.

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Familial Advanced SleepPhase Syndrome

An autosomal dominant disorder characterized by a very unusual sleep-wake cycle (fall asleep at 7:30 pm and wake up at 4:30 am)

Affected members of a large family enabled researchers to identify the first “clock” gene in humans- The period gene enables a person to respond to day and night environmental cues

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Human intelligence, mental quality that consists of the abilities to learn from experience, adapt to new situations, understand and handle abstract concepts, and use knowledge to manipulate one’s environment. (Encyclopædia Britannica)

Intelligence has been defined in many different ways, including the abilities, but not limited to, abstract thought, understanding, self-awareness, communication, reasoning, learning, having emotional knowledge, retaining, planning, and problem solving. (Wikipedia)

Intelligence

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IntelligenceA complex and variable trait subject to multiple

genes, environmental influences, and intense subjectivity

The IQ (intelligence quotient) test was first developed in France in 1904

- To predict academic success of developmentally disabled children

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IntelligenceThe IQ test was modified at Stanford University to

assess white, middle-class Americans• tests verbal fluency • mathematical reasoning• memory• spatial visualization ability

Understanding memoryhttp://www.youtube.com/watch?v=grZuwo_YlY0&fe

ature=related (3:47 mins)

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The IQ TestIQ is normally distributed around a mean of

100▪ Below 50 = Severe mental retardation▪ 50-70 = Mild mental retardation▪ 85-115 = Average intelligence▪ Above 115 = Above average intelligence

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Drug AddictionCompulsively seeking and taking a drug

despite knowing its adverse effectsSerotoninhttp://www.youtube.com/watch?v=iLVxickzsNs

Characteristics:- Tolerance = The need to take more of a drug to achieve the same effect

- Dependence = The onset of withdrawal symptoms with cessation of drug

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Proteins Involved in Drug Addiction• Enzymes involved in biosynthetic

pathways of neurotransmitters

• Neurotransmitter-reuptake transporters

• Cell-surface receptors

• Members of signal transduction pathways in postsynaptic neuron

http://www.youtube.com/watch?v=EdCmHRMhjoE&NR=1&feature=endscreen

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Drug AddictionHeritability is 0.4-0.6

- Twin and adoption studies support role of genes in drug addiction

Drug addiction produces long-lasting changes in the brainBrain changes that contribute to addiction are in the limbic

systemhttps://www.youtube.com/watch?v=GDlDirzOSI8 (Khan

Academy)http://www.youtube.com/watch?v=BHfOui9hSg4&NR=1http://www.youtube.com/watch?v=g6KpIrKCDwg&NR=1

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The Events of Addiction

Figure 8.6

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Drugs of AbuseAbused drugs are often derived from plants

- Cocaine, opium, and tetrahydrocannabinol (THC), the main ingredient in marijuana- These chemicals bind receptors in human neurons

Endorphins and enkephalins are the human equivalents of opiates - Are pain relievers

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Mood DisordersMood disorders represent the extremes of

normal behaviorhttp://www.youtube.com/watch?v=CDK50WQEOJc

The two most prevalent are:- Major depressive disorder = Marked by unexplained lethargy, sadness, and chronic depression

- Bipolar affective disorder = Marked by depression interspersed with mania (obsession, craze)

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Major Depressive Disorder

• Affects 6% of the US population

• A likely cause is a deficiency of the neurotransmitter serotonin, which affects mood, emotion, appetite, and sleep

• Many antidepressant drugs are selective serotonin reuptake inhibitors (SSRIs)

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Major Depressive Disorder

Figure 8.7

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Bipolar Disorder

Also called manic-depression

Affects 1% of the population

Associated with several chromosome sites

Its genetic roots are difficult to isolate

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Schizophrenia

Loss of ability to organize thoughts and perceptions – withdrawal from reality Worldwide – 1% affectedTypically early adult onset

Progression • Difficulty paying attention• Memory and learning difficulties • Psychosis (delusions and hallucinations)

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SchizophreniaDisjointed drawings by schizophrenic

patients display the characteristic fragmentation of the mind

Figure 8.8

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Schizophrenia• A heritability of 0.8 and empiric risk values

indicate a strong genetic component for schizophrenia

• Dozens of genes may interact with environmental influences to cause this disease

• One powerful candidate is infection during pregnancy- Prenatal exposure to the influenza or herpes viruses

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AutismAutism is a spectrum of disorders

- Characterized by loss of language, communication, and social skills, beginning in early childhood- Seizures and mental retardation may occur

Autism affects 3-6 children out of every 1,000- It strikes four times as many boys as girls

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AutismAssociated with many genes involved in neurotransmission

(cell communication) involved with human communication, learning, and memory

- Mutations - Level of expression of genes- Lack of pruning of nerve cells

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AutismIn 2014, massive sequencing studies of 20,000 revealed key autism

genes pointing to two key functions: • communication between neuronal junctions, or synapses• control of gene structure and expressionhttps://spectrumnews.org/news/massive-sequencing-studies-reveal-key-autism-genes/- cell adhesion proteins neurexins and neuroligins that are

necessary for synapse formation

- Other studies point to Extra Synapses in Brain that are not pruned

https://www.youtube.com/watch?v=gFIB7ovqL_k

https://www.scientificamerican.com/article/the-real-reasons-autism-rates-are-up-in-the-u-s/

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Understanding AutismAutism may arise from failure of synapses to form

that enable a child to integrate experiences

Figure 8.9