1. Neurons transmit messages and neuroglia support neurons physically and physiologically.
2. Behavioral traits are nearly always multifactorial because they reflect the complex interaction of genetic factors, responses to environmental stimuli and learned behaviors.
3. Neurotransmission and signal transduction
4. Environmental factors can alter the methylation patterns of genes whose protein products are active in the brain.
5. The phenotype is very specific and the consequence of an identified mutation in the period 1 gene. The family members are affected in a Mendelian pattern.
6. PTSD and the gene FKBP5 . Narcolepsy and the hypocretin gene. Familial advanced sleep phase syndrome and period 1 . Alcohol dependence and drug addiction and the dopamine
D(2) receptor gene. Major depressive disorder and the serotonin transporter gene.
Schizophrenia and the methyltransferase gene. Autism and neurexin and neuroligin genes.
7. Mutations in the genes that encode either of two of the five subunits of the nicotinic receptor can predispose an individual to developing a smoking addiction by releasing dopamine.
8. Many genes contribute to behavioral conditions, to different degrees, and may not affect the phenotype unless certain environmental situations are present. Symptoms tend to be shared among more than one condition, and individuals can have symptoms based on imitating affected relatives, not necessarily inheriting a causative genotype.
9. Early thoughts on the inheritance of intelligence did not consider women, equated fame with intelligence, and later on development of IQ tests did not account for societal disparities.
10. Intelligence manifests in many ways, and is influenced by many factors.
11. Tolerance and dependence
12. Opiates bind receptors for endorphins and enkephalins and relieve pain. Nicotine causes dopamine release from nicotinic receptors. SSRIs increase serotonin availability in synapses.
13. Exome sequencing is used to identify inherited recessive alleles or de novo dominant alleles that cause or contribute to autism.
14. THC, cocaine, and opium bind to receptors on human neurons.
15. Maternal infection or starvation during pregnancy.
16. For autism, empiric risk among siblings of affected children is 15 percent. Exome sequencing reveals the genes that contribute to autism in specific cases.
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17. Multiple unrelated affected subjects” compares sequences from many unrelated affected individuals to healthy reference genomes. “Trio analysis” compares sequences in parentchild trios. “Recessive analysis” compares DNA sequences in families in which more than one child has autism but the parents do not, to seek recessive alleles that cause the condition when homozygous or paired.
18. Neurexins and neuroligins affect glutamate neurotransmission. Misfolding due to mutations disrupts this process. If this occurs during early childhood it could interfere with how a child learns to make sense of the environment, with lasting effects.
1. Enzymes that control leptin and ghrelin production.
2. Sexual behavior and parenting ability have environmental components too.
3. Use the period 1 protein or enzyme in its synthetic or degradation pathway as a drug target to help people other than the rare families with sleep disorders.
4. A different gene encodes each subunit. If one is abnormal, interactions with others to form the intact receptor may be affected in a way that impairs functioning.
5. A GWAS might identify combinations of gene variants that people with sex addiction uniquely share. Perhaps variants of other genes associated with drug addictions are also more likely to be present in people with sex addiction. Another type of study might evaluate shared environmental influences, such as dissatisfaction with marriage. It would also be interesting to evaluate women for sex addiction, and homosexuals as well as heterosexuals.
6. A genetic test indicating increased risk for drug addiction could warn an individual or her parents to avoid situations or behaviors that encourage unnecessary drug use, or it can be harmful if the person gives up, thinking she or he cannot avoid fate.
7. There might be different types of depression or bipolar disorder, causing the same symptoms but via different combinations of gene variants.
8. Environmental component about equals genetic susceptibility. People growing up with parents who have schizophrenia might consider the behavior normal and imitate it.
9. a. Environmental b. exposure to chemicals or folic acid (see Case Studies and Research
Results #1); improved or broadened diagnosis; increased awareness and therefore more testing.
10. CHRNA3 , CHRNA5 , and CHRNB3 encode parts of the nicotinic (cholinergic) receptor, which affects the release of dopamine, which causes the pleasure associated with smoking.
CLCA1 , KCNJ6 , and TRPC7 encode ion channels, and variants might affect side effects such as respiratory distress following smoking. CTNNA3 encodes cadherin-associated protein, which may affect response to toxins. GABRA4 encodes a receptor for the neurotransmitter GABA, which has widespread effects on brain function. NRXN1 encodes a neurexin, a type of protein in synapses between brain neurons.
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1. Depression and sleep genes:
BMAL1, NR1D1, DBP, BHLHE40, BHLHE42 encode transcription factors that control “clock” genes and PER1, 2, and 3 maintain circadian rhythms, including sleep.
2. Genes that have mutations associated with intellectual disability:
FMR1 causes fragile X syndrome
ARID1B ID, short, low ears, developmental delay (autism part of syndrome)
EFTUD2 ID, developmental delay, microcephaly (part of mandibulofacial dysostosis)
SCN2A sodium channel disruption, seizures
SMAD4 part of Myhre syndrome (ID, short, deaf, bleeding)
3. Genes whose variants might contribute to autism:
AFF2 , CAPRIN1
AMT linked to FMR1 (fragile X syndrome) seizures and infant death
CHD7
FOXP1
GRIN2B
KCNQZ
LAMC3
MECP2
NLGN1
NRXN1
PEX7
POMGNT1 disrupts synapses speech glutamate receptor (neurotransmission) seizures laminin; neuron extensions causes Rett syndrome neuron cell adhesion disrupts synapses in brain seizures, cataracts, abnormal bones, death muscle-eye-brain disease with ID
SCN1A, SCN2A
SYNE1
VIP
VPS13B sodium channels, seizures bipolar, motor problems, mild versions cause autism social/cognitive problems
Cohen syndrome (ID, obese, painful joints, microcephaly)
4. The German Mental Retardation Network describes comparing exome sequences in parentchild trios to find ID-associated gene variants that arose de novo in the children. (see http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)61480-9/fulltext )
5. Chantix binds nicotinic receptors so nicotine cannot bind and release dopamine.
1. a. A defense attorney might try to use genotyping data to argue that a suspect is not responsible for his or her actions. b. Perhaps a range of levels of the enzyme is required for normal behavior, and either above or below it contributes to poor impulse control and violent tendencies. c. Behavioral genotyping is problematical because certain genotypes are also found in individuals who do not commit crimes. It also may fall into genetic determinism, absolving someone from taking responsibility because of a genotype.
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1. a. correlation (an association that is dose-dependent) b. A population study to compare the percent of mothers of children with autism who took folic acid throughout pregnancy to the percent of mothers of a control group of children who do not have autism who took folic acid throughout pregnancy. c. Conduct experiments in mice with folic acid discontinued beginning on every day of pregnancy, to reveal the critical period for causing autistic behaviors. Do a parallel study on humans (women who stopped folic acid on particular days). d. These conclusions are not valid for predicting autistic behaviors because the human brain develops throughout gestation, not just during the first 8 weeks the study covered. e. The folic acid hypothesis includes a plausible mechanism: altered methylation, and it has been modeled in mice. The vaccine hypothesis has many flaws, including the fact that autism has soared since the suspect vaccine component was removed years ago. f. Investigate whether limiting folic acid in the diet of a child with autism is helpful, although this might be risky because it is a vitamin.
2. a. Environmental b. Increased awareness and better screening c. Testing for a SNP profile associated with bipolar disorder or for variants of specific genes. Non-genetic cause. Genes may underlie the behavior that is modified by environmental factors.
3. Compare response to smoking cessation medications between 100 individuals who have the CYP2A6 fast metabolizer gene and 100 who do not using a case-control design. Each individual in the CYP2A6 fast metabolizer group is matched with an individual in the control group who shares as many characteristics as possible, including age, sex, activity level, and environmental exposures.
4. Because hypocretin when underexpressed causes sleepiness, its action should be blocked to alleviate insomnia.
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