Dissertations / Theses on the topic 'Behavioral genetics'

Neurodevelopmental disorders (ND) present a significant burden on society as over 5% of the US population is diagnosed with a ND. While environmental and biological factors have been associated with some cases of NDs, many still have unknown etiology. Strong comorbidities of NDs have been shown suggesting common biological processes of disease development. Sequencing technologies have allowed for the unprecedented identification of new candidate genes associated with NDs and many genes have been linked to multiple NDs. Developing robust methods to functionally validate these candidates is a critical next step for aiding patients with NDs. Using the zebrafish (Danio rerio), we characterized the developmental requirement of epilepsy candidate genes in the context of gene knockdown (KD). We demonstrated three different larval responses to pentylenetetrazol (PTZ) (hyperactive, hypoactive, or the same as control). We characterized the two genes resulting in a hyperactive response, Zinc Finger Homeobox 3 (ZFHX3) and Spectrin Repeat Domain Containing Nuclear Envelope Protein 1 (SYNE1), in greater detail. ZFHX3 is expressed in distinct brain regions during development and shows strong expression along nerve fiber tracts. SYNE1 shows broad expression during development that is enriched in the brain. Using CRISPR/Cas9 we generated a predicted null SYNE1 allele and recapitulated the seizure sensitivity phenotype in mutant larvae. Using a 60-hour behavioral assay we also demonstrate a generalized daytime hyperactivity in SYNE1 mutants. Our studies confirm ZFHX3 and SYNE1 as strong candidates for further study in epilepsy and suggest a role for SYNE1 in multiple NDs such as autism and attention-deficit/hyperactivity disorder.

Parenting behaviors and a variety of behavioral problems in children covary. The current study first aimed to examine how and why parenting and child behavioral problems are linked in middle childhood. In particular, a longitudinal design (1364 children assessed from 54 months to 5th grade) was used to examine whether the developmental link between parenting and child behavioral problems were reciprocal. A twin design (131 pairs of monozygotic and 173 pairs of dizygotic twins assessed from 6 to 8 years of age on average) was used to examine the underlying genetic and nongenetic etiology of this link. In addition, using these two samples, the current study also aimed to examine whether parental attributes, including negative affect, executive function, and social cognitive factors, modulate the link between parenting and child behavioral problems. Results across these two studies suggested that parenting and child behavioral problems mutually influenced the development of each other over time, potentially through both evocative and passive gene-environment correlation processes and environmental transmissions. In addition, maternal dispositional anger modulated the effects of child behavioral problems on changes in maternal parenting quality over time. Finally, implications of the current study were also discussed.
Ph. D.

Molecular Biology and Genetics
M.S.
Obesity rates are rising rapidly in the United States, reaching epidemic proportions. Insights into which genes predispose individuals to develop obesity are a necessity. If people at risk for obesity can be identified, individualized treatment programs can be designed based on the individuals' genetic and epigenetic predisposition to help decrease the rate of obesity and obesity-related diseases and deaths. This study will be focusing on the genes FTO, MAOA, SH2B1, CCKAR, NEGR1, LEPR, DNMT3B, and BDNF that have been previously associated with obesity risk and obesity-related phenotypes. Transcript levels of FTO and MAOA were analyzed using quantitative real-time RTPCR, promoter methylation was examined utilizing methylation-sensitive restriction enzyme digestion assays designed for each of the eight gene promoters, and the genotype at eight SNPs, previously associated with obesity, were examined. These data were compared to data gathered on body composition, eating behavior, and temperament. The goals of this project were to replicate results from previous research suggesting associations between certain genetic variants to body composition measures, to identify novel associations between genetic and epigenetic variations and body composition, eating behavior, and temperament, and to provide evidence that the genes previously correlated to obesity in adults is also correlated to measures of obesity and obesity-related phenotypes in children. Decreased levels of methylation in the promoter of BDNF were associated with different eating behaviors including, decreased food fussiness and decreased satiety response. These results were statistically significant after Bonferroni correction for multiple testing. Genotype analysis at the SNP, rs4923461, in BDNF identified an association between the G allele and increased emotional under-eating in males. This association also remained significant after Bonferroni correction. These data gathered for BDNF may suggest a novel role for BDNF in the regulation of energy balance and obesity. The data analysis for all expression, methylation, and genotype data identified associations with 16 different obesity-related phenotypes. These phenotypes included; three measures of body composition, seven eating behaviors, two measures of food intake, one measure of self-regulation, and three measures of temperament. These associations were held to a lower statistical standard and are considered suggestive pending replication in a larger sample. This research was able to provide novel insight into genetic and epigenetic alterations that modify obesity-related phenotypes in African American children. A cumulative genetic and epigenetic "obesity risk factor" score was derived using all significant and suggestive associations to obesity-related phenotypes. The score was derived from the methylation analysis from all eight gene promoters, SNPs from LEPR, DNMT3B, and BDNF, and expression data for MAOA and FTO. The "obesity-risk factor" score was significantly higher in obese compared to non-obese individuals, suggesting the combined genetic and epigenetic approach has value in the prediction of childhood obesity in African Americans.
Temple University--Theses

The mechanisms of learning and memory are fundamental to our understanding of brain function. The aim of this thesis is to characterize the molecular, cellular and behavioral mechanisms underlying the aversive olfactory learning in the model organism C. elegans, to gain insight into animal learning in general. At the molecular level, I focused on the function of the transforming growth factor-\(\beta\) \((TGF-\beta)\) signaling pathway. The \(TGF-\beta\) pathway is conserved throughout the Metazoa and is critical for diverse physiological processes. It has also been implicated in neural plasticity, but the exact mechanisms remain elusive. Utilizing a behavioral assay that measures adult olfactory learning, I have found that DBL-1, a C. elegans \(TGF-\beta\) homolog, is required for learned olfactory avoidance of pathogenic bacteria. Mutations in DBL-1 signal transduction pathway, including those in the dbl-1 ligand, sma-6 and daf-4 receptors, and sma-3 SMAD, abolish the learning ability of adult animals. I have identified AVA neurons, a pair of command interneurons critical for olfactory sensorimotor response, as the essential release site of DBL-1 ligand in regulating learning. AVA neuronal activity is repressed by training, accompanied by an increase in the amount of DBL-1 secreted from AVA neurons after training. Remarkably, artificial inhibition of AVA activity in the absence of training is sufficient to increase AVA secretion of DBL-1, supporting a model in which experience dependent changes in neuronal activity lead to altered DBL-1 \(TGF-\beta\) signaling. Downstream of DBL-1 ligand, I found that the type I receptor SMA-6 primarily acts in the hypodermis to promote olfactory plasticity at the adult stage. At the behavioral level, I examined the taxis behavior of C. elegans toward different bacteria and the effect of training on its taxis strategy. Preliminary results suggest that C. elegans may be capable of modulating its olfactory preference by means of differentially adjusting its navigation strategy. In summary, this thesis uncovered the critical role of DBL-1 \(TGF-\beta\) signaling in C. elegans learning, and alterations in behavioral components underlying olfactory plasticity. These findings are expected to shed light on learning and memory in other animals as well.

I investigated patterns of genetic variation in the North American gall-forming aphid, Pemphigus obesinymphae. In Chapters 2a and 2b, I developed and then implemented clone-specific molecular markers to investigate clonal mixing in P. obesinymphae . During its gall-forming phase, P. obesinymphae clones produce aggressive larval "soldiers", which altruistically defend their colonies from natural enemies. I showed that movement occurs between galls, indicating that P. obesinymphae colonies are not pure clones. I also showed that intruders behave selfishly, by not defending unrelated clones, and by accelerating development into reproductive adults. These results reveal a greater degree of complexity and conflict in aphid social groups than previously known. In Chapter 2c, I surveyed molecular variation in P. obesinymphae and its bacterial endosymbiont, Buchnera aphidicola. I found levels of variation at two Buchnera loci to be similar to those estimated from a previous study on a distantly-related aphid, Uroleucon ambrosiae. In the western US, P. obesinymphae and B. aphidicola were nearly monomorphic, and in the eastern US, estimates of synonymous divergence ranged from 0.08 to 0.16%. Most polymorphisms in sub-populations at low frequencies, indicating a recent purge of ancestral polymorphism. These results emphasize the importance of aphid population biology in shaping evolutionary patterns in B. aphidicola. In Chapter 2d, I explored the role of life cycle variation in speciation between Pemphigus aphids. P. obesinymphae and P. populi-transversus are closely-related and sympatric on the cottonwood, Populus deltoides (Salicaceae), but they have distinctly different life cycles. P. populi-transversus has a sexual stage that occurs in the fall, while P. obesinymphae produces sexuales in late spring. Field evidence indicates that intermediate phenotypes rarely occur, and mitochondrial and bacterial endosymbiont DNA sequences show no maternal gene flow between the two species. I considered the possibility of an initial allopatric phase in the divergence, and discuss the sequence of evolutionary changes that likely led to the sympatric divergence of P. populi-transversus and P. obesinymphae. The most plausible interpretation of available data is that a shift in timing of the life cycle in an ancestral population spurred divergence between the species pair.

The overall aims of this thesis were to investigate psychological and behavioral effects of receiving cancer genetic counseling for breast, ovarian and colorectal cancer and/or with a family history of these cancer types and to determine whether counselees’ informational needs were met. Study I was performed 3-7 years post-counseling. Participants (n=214) reported a relatively high level of anxiety but a low level of depression compared to cancer patients in general. However, there was no indication that the distress experienced was due to the counseling. Moderate changes in life and family relations, high level of adherence to recommended controls and satisfaction was reported. Study II was a randomized control trial (RCT) intervention study which involved 147 counselees. An increase in the level of knowledge and correct estimation of personal risk was reported in both the intervention and control groups, although this increase declined at later follow-up. Enhanced information led to significantly greater satisfaction with the given information, and the way of informing relatives. Most counselees had shared information with their at-risk relatives. Study III focused on sharing information with at-risk relatives among participants in study II and their relatives (n=81). Counselees were interviewed and answered a questionnaire, whilst their relatives only answered the questionnaire. Counselees reported positive/neutral feelings about communicating genetic information and mostly interpreted their relatives’ reactions as positive/ neutral. Also, approximately 50% of relatives reported positive/neutral reactions and were generally satisfied with the received information. Study IV was conducted in Sweden and Norway based on 235 counselees. Counselees expected counselors to be skillful and thoughtful, take them seriously and provide risk estimations and medical information. Most important issues to counselees were satisfactorily addressed by the counselors. Analyzing importance rankings resulted in five categories of needs: a need for facts, caring communication and medical information, need for understanding and support in sharing genetic information, practical care and medical/practical information. In conclusion, no adverse psychological or behavioral effect on counselees was observed. Apparently, genetic counseling is managed properly and counselors successfully address counselees’ needs. Providing extended information does not seem necessary, however, tailoring information to individual counselees needs may create a more effective counseling.

Similar to the pattern observed in people with substance abuse disorders, laboratory animals will exhibit escalation of cocaine intake when the drug is readily available and will exhibit increased drug-seeking behaviors after long periods of abstinence. Additionally, there are long term changes in neuron structure, receptor function, and neurotransmission associated with abstinence from cocaine in humans and animals. DNA methylation is an epigenetic modification to the DNA structure that mediates mRNA expression to confer different cell types, but has recently been implicated in learning and memory mechanisms. The long-term control that DNA methylation has over gene expression in animals makes it a prime candidate for controlling gene expression over the course of abstinence in animals with previous drug experience. Therefore, here, I investigated the contribution of behavioral contingency of cocaine administration on escalation of cocaine intake and re-exposure to cocaine cues as well as DNA methylation and gene expression within the dorsal medial prefrontal cortex (dmPFC) in adult male Sprague-Dawley rats. I exposed rats to daily training for saline (1 h/ day) or cocaine (0.25 mg/kg/inf) in limited- (1 h access per day), prolonged- (6 h access per day), or limited + yoked-access (1 h contingent + 5 h non-contingent access per day) for 15 days. Rats were then put through forced abstinence for 1, 14, or 60 days, and then the dmPFC was dissected out. Saline- and prolonged-access rats were additionally separated into cue- and no cue- conditions after 60 days of abstinence, where cue rats were re-exposed to the operant chamber without cocaine delivery for 2 h. These studies led to 4 main findings. 1) cocaine contingency affects mRNA expression for glutamatergic genes, 2) DNA methylation changes dynamically throughout abstinence, 3) re-exposure to cocaine cues rapidly alters DNA methylation and mRNA expression, and 4) DNA methylation, hydroxymethylation, and transcription factor binding all contribute to altered mRNA expression.

Impairments in various aspects of language, including the manipulation and comprehension of verbal and written language, are common in pediatric populations. Some disorders of language are secondary to other clinical presentations, while others, such as dyslexia (or reading disability [RD]), language impairment (LI), speech sound disorder (SSD), and autism spectrum disorders (ASD), have primary deficits in language skills. Each of these is a distinct disorder with unique clinical presentations and deficits. For instance, children with RD have deficits in reading and the use of written language, while those with LI have deficits in the manipulation and comprehension of verbal language. Additionally, children with SSD have difficulties in the production of speech sounds, while children with ASD may have delays or regressions in language and an inability to use complex, proper syntax and pragmatics. However, there is substantial comorbidity of these disorders, as children affected with one of these disorders are more likely to have or develop another disorder than their typically developing peers. These 'disorders—RD, LI, SSD, and ASD—are complex traits, with significant environmental and genetic components contributing to each. Similar to their phenotypic relationships, there is limited evidence that these disorders may share genetic contributors. In fact, these shared genetic components may explain the common phenotypic comorbidities of these disorders. Therefore, the overall goal of this project is to determine whether and to what extent RD, LI, SSD, and ASD share genetic associations with the hypothesis that these disorders have common genetic contributors. To accomplish this goal, I assess whether genetic associations were shared among these disorders or specific to individual disorders. First, I expand the association of the RD environmental risk factor, prenatal exposure to nicotine, to include LI and show the association of dopamine-related genes ANKK1 and DRD2 to LI. Second, two RD risk genes, DCDC2 and KIAA0319, located within the DYX2 locus on chromosome 6p22, show associations with both LI and SSD. Third, I identify ZNF385D as a novel risk gene for subjects affected with comorbid RD and LI. I also assess the neuroimaging implications of DYX2 genes and ZNF385D, specifically in regards to cortical thickness, fiber tract volume, and fractional anisotropy. Finally, two LI risk genes, ATP2C2 and CMIP located within the SLI1 locus on chromosome 16, are associated with language skills of subjects with ASD. Taken together, these results characterize the relationship of previously identified risk genes to other related language disorders and identify novel risk genes that specifically contribute to language comorbidity. Shared genetic associations among these language disorders appear to be commonplace as opposed to the exception. However, the question remains of how these genetic variants interact with each other and other genes/exposures to ultimately lead to one or more of these language deficits seen clinically.

Doctor of Philosophy
Department of Biology
Brett K. Sandercock
Samantha Wisely
Anthropogenic activities and climate change have dramatically altered landscapes worldwide. The ability of species to cope and adapt to ongoing changes is likely a function of their behavior, movements, and sensitivity to fragmentation. Greater Prairie-Chickens (GPC) are a lek mating grouse native to the Great Plains Landscape Conservation Cooperative (GPLCC), for which inbreeding depression and anthropogenic avoidance are a concern. The goals of my dissertation were to: 1) identify genetic correlates of male performance which may influence population viability under current land use practices, 2) identify GPC habitat characteristics and delineate areas of critical GPC habitat necessary for GPC conservation, and 3) identify the relative importance of distance and habitat quality for maintaining genetic connectivity among spatially structured populations. First, I found male reproductive success and survival to be positively associated with genetic diversity. Using multistate modeling in Program Mark, male survival across the observed range of variation in number of alleles (15-22) increased more than fourfold from 0.17 to 0.77. Second, I found 35-40% of Kansas, and 1.5 % (11,000 Km squared) of the GPLCC, were considered high-quality lek habitats. Top performing logistic models predicting lek presence (wi=0.95) included strong effects of grassland cover and avoidance of anthropogenic disturbance. When this model was applied to putative future landscapes based on climate change and current land use trends over a 70-year period, I found a 27-40% reduction in habitat area and a 137 Km southeast shift in habitat distribution. Under equilibrium conditions we expect isolation by distance (IBD) to explain the distribution of genetic diversity. However, if the landscape restricts dispersal, then we might observe isolation by resistance (IBR). I used model selection procedures to choose among competing IBR or IBD models to explain the distribution of genetic diversity among GPC populations across Kansas and the GPLCC. IBD was never supported (R-square<0.02, P>0.09). The best models for Kansas (R2=0.69, P<0.02) and for the GPLCC (R-square=0.46, P<0.02) indicated that human-mediated landscape changes have influenced landscape permeability for dispersal. The integration of behavioral, landscape, and genetic data provided new insights on prairie-chicken ecology, and is a powerful approach for developing conservation strategies for sensitive species.

Animals switch between periods of behavioral quiescence and arousal in response to environmental, circadian, or developmental cues. C. elegans exhibit periods of behavioral quiescence during larval molts (termed lethargus) and as adults. Little is known about the circuit mechanisms that establish these quiescent states. Mutants lacking the neuropeptide receptor NPR-1 are a model for heightened arousal and have dramatically reduced locomotion quiescence during lethargus as a result of increased sensory acuity and secretion of the arousal peptide PDF-1. In Chapter 2 of this thesis, we show that the aroused locomotion of npr-1 mutants results from the exaggerated activity in multiple classes of sensory neurons, including nociceptive (ASH), touch sensitive (ALM and PLM), stretch sensing (DVA) neurons, and chemosensory neurons (ASI). These sensory neurons accelerate locomotion via both neuropeptide and glutamate release and their relative contribution to arousal differs between larval molts and adults. These results demonstrate that a broad network of sensory neurons and transmitters dictates transitions between aroused and quiescent behavioral states. We propose that locomotion quiescence during molts is mediated by diminished sensory inputs (termed sensory gating) and that NPR-1 plays a central role in this process. In Chapter 3, we identify a second arousing neuropeptide, FLP-2, which promotes locomotion through an orexin-like receptor (FRPR-18). FLP-2 secretion is inhibited by NPR-1 and enhanced secretion is associated with aroused locomotion during molts. This locomotion arousal is stabilized by reciprocal positive feedback between two arousing neuropeptides (FLP-2 and PDF-1). FLP-2 and FRPR-18 are co-expressed in ASI neurons, suggesting that ASI activity is regulated by autocrine positive feedback. Our results suggest that FLP-2 and FRPR-18 are the C. elegans homologs of mammalian hypocretin/orexin peptide and receptor, respectively. We propose that aroused locomotion is stabilized by two circuit motifs: reciprocal positive feedback between different classes of arousing neurons and autocrine positive feedback of FLP-2 expressing neurons. These motifs may be conserved in the arousal circuits of other model systems.
Medical Sciences

Eastern and Carolina hemlock in the eastern United States are experiencing high mortality due to the invasive non-native hemlock woolly adelgid (HWA). The most promising means of control of HWA is the importation of natural enemies from the native range of HWA for classical biological control. Prior to release, natural enemies must be tested for suitability as a control agent, including the ability to locate the target prey. Coleopteran predators, including Scymnus coniferarum and Laricobius osakensis are under consideration as a means of biological control of HWA. Laricobius nigrinus was released in hemlock forests in 2003. It was recently discovered to hybridize with the native Laricobius rubidus. Behavioral responses of these predators to HWA and host tree foliage were observed using a 4-chambered olfactometer, and genetic analysis was used to differentiate responses of L. nigrinus, L. rubidus, and hybrids. In the olfactometer, insects are allowed to amble about the arena and respond to volatile cues from each treatment. Host foliage with and without HWA was tested, as were various comparisons of eastern versus western foliage, host versus non-host foliage, and foliage containing HWA and a congeneric feeding beetle. Olfactometer bioassays demonstrated that foliage from hosts where prey is commonly found is preferable to foliage where prey is seldom found, and that the presence of HWA-induced volatile cues is the strongest driver of behavior, and trumps the presence of a competitor. There is evidence in the study that supports the reliability-detectability phenomenon common in parasitoid biological control agents. Hybrid individuals were found to behave similarly to released L. nigrinus, although in some cases intermediate behavioral traits were evident, with respect to the parental species. This study and others support the continued need for strict testing of potential biological control agents prior to release, as well as a strong impetus for the inclusion and implementation of genetic analysis as a standard component of agent evaluation.

There is a growing body of evidence that normal nervous system activity requires signals from resident microbes. We have yet to discover the mechanisms by which the microbiota influence brain function. However, we know that the enteric nervous system (ENS) serves as an important interface between the developing host and its microbiota. In this dissertation I will introduce a novel computer-assisted method for ENS characterization and a novel, incredibly specific mechanism of host-microbe interactions. With new ENS characterization method I developed, it will be possible to better understand the role of the ENS during development, by more rapidly and algorithmically assessing ENS phenotypes. Furthermore, my discovery of a single microbially-sourced protein that influences vertebrate host prey capture behavior and visual system development, will provide a new appreciation for the role resident microbes, both in model organisms and in ourselves. By both establishing a new, less biased, approach to image analysis and describing a surprising new regulatory host-microbe interaction, the work I describe in this dissertation should provide the foundation for an explosion of exciting discoveries in the near future.

Developmental language impairments are neurodevelopmental disorders in which the acquisition of language, a task which children typically perform with ease, is hindered or fraught with difficulty. This work focuses on specific language impairment (SLI), a common and highly heritable language impairment in which language development is abnormal while other developmental domains are normal. Additionally, a case-study of a child with a broader linguistic and behavioural phenotype is also presented. The work described in this thesis includes both genetic and functional investigations which were aimed at identifying candidate genes for language impairment and provide insight into the genetic mechanisms that underlie language development. I performed a genome-wide association study of SLI which included child genotype effects, maternal genotype effects, parent-of-origin effects, and maternal-foetal interaction effects. This study found significant paternal parent-of-origin effects with the gene NOP9 on chromosome 14, and suggestive maternal parent-of-origin effects with a region on chromosome 5 which had previously been implicated in autism and ADHD. Case-control and quantitative association analyses of HLA genes and SLI identified several risk alleles and protective alleles. A case-control association analysis for related individuals which used an isolated population affected by SLI identified a non-synonymous coding variant in the gene NFXL1 which was significantly more frequent in affected individuals than in unaffected individuals. High-throughput sequencing of the coding regions of NFXL1 and LD blocks surrounding associated variants in ATP2C2, CMIP and CNTNAP2 (as reported in previous studies) identified novel or rare non-synonymous coding variants in NFXL1 and ATP2C2 in SLI families as well as intronic variants in all four genes that were significantly more frequent in SLI probands than in population controls. I describe a functional study of NFXL1 examining its expression in various brain regions, the presence of different splice variants across several tissues, its effect on genes it potentially interacts with, and the subcellular localisation of the protein. Finally, I present the case-study of a child with language impairment who had chromosomal rearrangements which spanned the location of FOXP2. I examine the potential influence the chromosomal rearrangements had on FOXP2 expression and describe a lincRNA gene which was disrupted by the chromosomal inversion. In conclusion, this work identified new candidate genes for language impairment, provided further support for the involvement of previously-identified candidate genes in SLI and contributed to the understanding of the molecular function of a newly-identified candidate gene for SLI.

Individual differences in initial sensitivity to ethanol are strongly related to the heritable risk of alcoholism in humans. To elucidate key molecular networks that modulate ethanol sensitivity we performed a systems genetics analysis of ethanol-responsive gene expression in brain regions of the mesocorticolimbic reward circuit (prefrontal cortex, nucleus accumbens and ventral midbrain) across the BXD RI panel, a highly diverse family of isogenic mouse strains before and after treatment with ethanol. Acute ethanol altered the expression of ~2,750 genes in one or more regions and 400 transcripts were jointly modulated in all three. Ethanol-responsive gene networks were extracted with a powerful graph theoretical method that efficiently summarized ethanol's effects. These networks correlated with acute behavioral responses to ethanol and other drugs of abuse. As predicted, networks were heavily populated by genes controlling synaptic transmission and neuroplasticity. Several of the most densely interconnected network hubs, including Kcnma1 and Gsk3-beta, are known to influence behavioral or physiological responses to ethanol, validating our overall approach. Other major hub genes like Grm3 and Nrg3 represent novel targets of ethanol effects. Networks were under strong genetic control by variants that we mapped to a small number of chromosomal loci. Using a novel combination of genetic, bioinformatic and network-based approaches, we identified high priority cis-regulatory candidate genes, including Scn1b, Gria1, Sncb and Nell2. The ethanol-responsive gene networks identified here represent a previously uncharacterized intermediate phenotype between DNA variation and ethanol sensitivity in mice. Networks involved in synaptic transmission were strongly regulated by ethanol and could contribute to behavioral plasticity seen with chronic ethanol. Our novel finding that hub genes and a small number of loci exert major influence over the ethanol response of gene networks could have important implications for future studies regarding the mechanisms and treatment of alcohol use disorders.

Increasingly, individual variation is being recognized as an important influence on behavioral evolution. Sources of variation are therefore an important target for research into the development, evolution, and function of behavior. By providing information about the timescale on which individuals are responsive to their environment, patterns of within-individual variation can shed light on function of behavioral variation. Here, I wanted to understand the function of behavioral variation and the genetic and environmental sources of variation in behavior. First, I test the hypotheses that variation in begging signals nestling hunger, need, or quality. Hunger is a short-term response to food deprivation, while need and quality give long-term information about fitness benefits of gaining more food and fitness potential, respectively. Second, I test the hypotheses that variation in begging is due to genetic, permanent environment, common environmental, and maternal effects. I test these hypotheses in the begging behavior of western bluebirds (Sialia mexicana), making repeated measurements across the nestling period. I show that begging behavior is consistent across the nestling period, and that nestling begging intensity increases with food deprivation. Nestlings fed during a given parental visit beg at higher intensity than nestmates, and on average wait longer since their last meal compared to individuals who were not fed in the same visit. These results support the hypothesis that variation in nestling begging signals hunger. I also show that responsiveness to food deprivation is negatively related to condition, but this effect is not consistent across the nestling period. Finally, variation in begging is produced by a common environmental effect that is correlated through time, suggesting that begging is strongly influenced by the nest environment. Together, these results indicate that variation in begging signals short-term changes in hunger and that environmental effects dominate the production of variation in begging.

The worm Caenorhabditis elegans is a well-studied model organism in numerous aspects of its biology. This small free living nematode has less than 1,000 cells, but shows clear conservation in both signaling and behavior to mammals in aspects of appetite control. This is of importance to humans, where failure of appetite control is a major factor in the unprecedented obesity epidemic that we see today.

In general, worm behavior reflects its internal nutritional state and the availability and quality of food. Specifically, worms show a behavioral state that mimics aspects of the mammalian behavioral satiety sequence, which has been termed satiety quiescence. We have used locomotion tracking and Hidden Markov Model analysis to identify worm behavioral state over time, finding quiescence along with the established worm locomotive behaviors roaming and dwelling. Using this analysis as well as more conventional cell biology and genetic approaches we have further investigated satiety signaling pathways. We have found that the neuron ASI is a major center of integration of signals regarding the internal nutritional state of the worms as well as the nutritional content of its environment. Our results show that cGMP causes levels of the TGFβ ligand to be increased in fasted worms, which is then released and binds to its receptor on the RIM and RIC neurons. This signaling connects nutritional state to behavioral response, promoting the sleep-like behavioral state satiety quiescence. Additionally, we have begun a candidate approach examining several other groups of signaling molecules for potential roles in satiety quiescence signaling including cannabinoids, multidrug resistance proteins, and neuropeptides. The result of this investigation is a better understanding of mechanisms of satiety quiescence signaling as well as a new tool that provides highly quantitative, unbiased, and automated data to aid in our ongoing work.

Isogenic, or inbred, mouse strains are currently the experimental subjects of choice in laboratory studies focused on genetics, pharmacology, and psychological issues. Understanding phenotypic differences in isogenic strains is important in order to interpret experimental results obtained from inbred mouse strains. Four commonly used inbred strains, C57BL/6NHsd (C57), DBA/2NHsd (DBA), 129S2/SvHsd (129), and Balb/cAnHsd (Balb/c), are investigated in this study using four different behavioral tasks that measure locomotor activity and cognitive behavior (Morris Water Maze (MWM), T-maze, and operant autoshaping procedures). In the locomotor activity task 129 mice showed significantly less horizontal ambulation than any other strain, while differences in rearing was seen between all strains, with C57 mice producing the most, and 129 showing the least rearing. Thigmotaxia was seen the most in the 129 strain, less so with the Balb/c and DBA strains, and the least in the C57 mice. In the MWM learning across strains was noted but there was no difference between the strains. In the T-maze the Balb/c strain showed the shortest latency to enter an arm, while the 129 strain showed the longest. As expected they also showed the lowest accuracy and the highest percent time-outs compared to all the other strains. In the autoshaping procedure little difference between the strains was observed. Balb/c mice trended graphically towards higher rates however there was no difference with regard to number of contingent responses or number per strain to reach a criterion of 10 or more contingent reinforcers. Finally, locomotor activity was measured again at the end of the study. The activity results were still similar, although the C57 strain showed a decrease in horizontal ambulation as compared to DBA and Balb/c strains; however, the 129 strain still showed the least activity. These results indicate that there are significant differences in locomotor behavior and cognitive processes in these strains that should be considered when interpreting results from studies using these inbred mouse strains.

Circadian clocks drive the daily patterns of behavior and physiology observed in most organisms. These internal clocks allow organisms to advantageously align their behavior to daily cycles in the environment such as light and temperature. The fruit fly Drosophila displays many robust, daily behavioral rhythms including discrete bouts of locomotor activity at dawn (i.e. morning activity) and dusk (i.e. evening activity). The molecular clocks that drive these daily activity bouts are found in approximately 150 circadian pacemaker neurons in the fly brain. Interestingly, the timing of the molecular clocks is synchronous between all pacemaker neurons, yet different subsets of these neurons appear to make quite different contributions to the regulation of morning vs. evening activity. It remains poorly understood how the molecular circadian clock drives daily rhythms in pacemaker neuron activity or how the activities of different groups of pacemaker neurons combine to produce complex behavioral output. The overall goal of this thesis is to characterize how different subsets of Drosophila pacemaker neurons contribute to daily behavioral regulation both individually and as a network. To examine daily patterns of neuronal activity in different groups of circadian clock neurons, we have established imaging methods using genetically encoded fluorescent sensors. For these sensors, changes in fluorescence levels correspond to changes in neuronal activity, thus allowing us to measure neuronal activity patterns in real-time and throughout the day. Using these tools, I have characterized the daily activity patterns of different groups of the clock neurons that agree with published rhythms in activity as assessed by patch-clamp electrophysiology and calcium imaging We have also used genetic and molecular approaches such as RNA interference (RNAi) to alter gene expression in a tissue-specific manner. These approaches allow us to manipulate the function of different groups of clock neurons and to determine how these manipulations affect rhythmic behavior and neuronal activity patterns. We have silenced different subsets of circadian pacemaker neurons using RNAi knockdown of the NARROW ABDOMEN (NA) sodium leak channel and identified a complex role for a subset of the posterior dorsal neurons 1 (DN1p) in regulating locomotor behavior. The DN1p are known to be involved in promoting morning behavior, and recent studies have shown that a subset of the DN1p regulate midday sleep bouts via downstream sleep regulating neurons. Our data suggest that the DN1p neurons likely suppress midday activity through inhibition of other circadian pacemaker neurons, and that this inhibitory role can be compensated for by light. Finally, we have also examined the intracellular mechanisms regulating circadian neuronal output. Rhythmic activity of the NA leak channel and its mammalian ortholog (NALCN) have been shown to contribute to daily excitability rhythms in circadian pacemaker neurons. We used temporally-restricted expression of RNAi and rescue constructs to identify a developmental requirement for the NA channel complex in Drosophila, and we demonstrate that channel complex proteins are very stable in the Drosophila brain. These data suggest that circadian regulation of the NA channel in adults may involve post-translational mechanisms that control activity and not just expression of the channel complex.

This study examined the role of birth complications, delinquent peers and siblings, and specific dopamine receptors on the development of externalizing behavior in children and adolescents, along with the role of heritability in aggression and delinquency. Specifically, it was hypothesized that increased birth complications, presence of specific dopamine receptor (DRD2 and DRD4) risk alleles, and delinquent peers or siblings would be related to increased externalizing behavior at follow-up. The sample consisted of 65 twin pairs, aged six to 16 (mean age = 9.06 years) who originally participated in the Southern Illinois Twins and Siblings Study (SITSS) at age five. Significant results were found for the stability of aggression from age five to follow-up and heritability of parent-rated aggression and delinquency measures was shown. Presence of delinquent peers or siblings was positively related to aggressive and delinquent behavior. Those with more delinquent peers and with the DRD2 risk allele were rated as more delinquent. In contrast, those without the DRD4 risk allele were also rated as more delinquent. Presence of birth complications was positively related to aggressive and delinquent behavior ratings by parents at follow-up. However, birth complications were negatively related to delinquency on youth-rated measures. Finally, those with fewer complications and more delinquent siblings engaged in more reported delinquent behavior. The present study provided important information concerning the effects of birth complications, delinquent peers and siblings, and specific dopamine receptors on the development of externalizing behavior in children and adolescents, along with the role of heritability in aggression and delinquency.

1. Introduction This dissertation consists of six chapters that span a very diverse set of topics. Yet, it has two unifying themes, economics and biology, that tie it together. The first four chapters present the principal findings from a project that was initiated jointly with David Cesarini and Magnus Johannesson, and that applies the twin method from behavioral genetics to economics. The last two chapters instead use a simple regression framework and evidence from biological anthropology to investigate recent claims regarding the effects of child bearing and past slave trades. 2. Genes and economics There is a small, but rapidly growing, literature studying the genetic and environmental origins of economic behavior and outcomes (Bowles et al., 2005; Beauchamp et al., 2011). Until recently, this literature focused exclusively on outcomes, and in particular income. In chapters 1-4 we instead focus on economic behavior and decision-making. Previous behavioral genetic work outside the domains of economics has changed the way that we think about a number of behavioral traits. In this literature it is typically found that i) variation is heritable ii) genetic factors are more important than family environment iii) a large fraction of variation cannot be explained by neither genes nor family environment (Turkheimer, 2000; Plomin et al., 2009). However, compared to many other disciplines, and psychology in particular, economics is lagging behind. In fact, as recently as 2009 the leading text book in behavioral genetics described economics as "still essentially untouched by genetic research" (Plomin et al., 2009, p. 353). Hopefully, the chapters in this dissertation can help to improve on this somewhat unsatisfactory state of the art. Chapters 1 and 2 study economic decision-making in the laboratory using the twin method. More specifically, we study the ultimatum and dictator games alongside risky gambles, using same-sex twin pairs as our subject pool. Given a few additional assumptions, the fact that identical twins have, in expectation, a twice as high coefficient of genetic relatedness as fraternal twins implies that we can study the genetic and environmental contributions to variation in behavior by studying twin correlations in observed choices. Chapters 3 and 4 apply the same method to actual portfolio choices associated with a far-reaching pension reform, as well as to a set of standard behavioral anomalies. Taken together, these four chapters provide strong evidence in favor of the hypothesis that genes influence economic decision-making. Thus, economic behavior does not appear to be much different from other types of behavior. 3. Economics and history The last two chapters of the dissertation turn to the past, rather than genes, in an effort to evaluate recent findings regarding two important welfare outcomes. In chapter 5 we investigate Nunn’s (2008) claim that past slave trades had a negative impact on current economic performance in Africa. By extending the sample period back in time we demonstrate that this relationship was not significant in 1960. In addition, by applying Nunn’s method to an episode of large scale slave raiding in Italy, we demonstrate that there exists a similar negative relationship across Italian regions, although it becomes insignificant when geographical controls are included. Intriguingly, going back to 1960, the coefficient on slave raids for Italy also has a similar time trend to that for Africa. Taking these facts, and our reading of the historical and anthropological literature, which is much different from that of Nunn, into account we do not find much support for the hypothesis that the African slave trades had a negative impact on current economic performance. Finally, chapter 6 investigates the large and negative relationship between giving birth to a son, rather than a daughter, and maternal longevity that was documented in a Sami hunter-gatherer population from Finland (Helle et al., 2002). Using a substantially larger sample of pre-industrial Swedish Sami we find no evidence in favor of such a relationship. 4. Brasklapp Five of the chapters in this dissertation (Ch. 1-4 & 6) are slightly altered versions of previously published papers (Wallace et al., 2007; Cesarini et al., 2009 a, b; 2010; 2011). Unfortunately, the fact that earlier versions of the chapters were prepared as separate articles for five different journals means that they can at times appear both repetitive, and in terms of notation and formatting, somewhat inconsistent. I apologize to the reader for these inconveniences.

Diss. Stockholm :  Stockholm School of Economics, 2011. Introduction together with 6 papers

Alcohol use disorder (AUD) is the fourth leading cause of preventable death in the United States, and the fifth leading risk factor for premature death and disability, globally. There are currently very few treatment options for AUD and there is a need for effective preventive and treatment strategies for this condition. AUD risk has a significant hereditary component, with the contribution of genetic factors being estimated to be about 50%. The Davies-Bettinger laboratory uses C. elegans as a model organism to study the contribution of genetic factors in modulating neuronal responses to ethanol. In this project, we examined the role of mitochondrial beta-oxidation of fatty acids (FA) in altering ethanol responses using loss-of-function (lf) mutants and RNAi-mediated knockdown of specific genes in this pathway. We tested a total of 34 genes and found that lf in 13 genes significantly affected ethanol response phenotypes. We conclude that mitochondrial beta-oxidation of FA is essential for ethanol response behavior in C. elegans. Further experiments need to be conducted to dissect the specific contribution of various components of mitochondrial beta-oxidation in modifying the neuronal responses to ethanol.

Thesis (Ph.D.)--University of Cincinnati, 2009.
Advisor: John P. Wright. Title from electronic thesis title page (viewed July 29, 2009). Keywords: low self-control; behavioral genetics; Mx; Gottfredson and Hirschi; general theory of crime; sex differences; biosocial criminology. Includes abstract. Includes bibliographical references.

Processes that influence the early life stages of fishes can significantly impact population dynamics, yet they continue to be poorly understood. This dissertation examined relationships between the environment, early life history traits (ELHTs), behavior, and post-settlement survival for a coral reef fish, Stegastes partitus, in the upper Florida Keys, to elucidate how they influence juvenile demography. Otolith analysis of settlers and recruits coupled with environmental data revealed that S. partitus surviving the early juvenile period settled at larger sizes and grew slower post-settlement. Water temperature also influenced the ranges of these and other ELHTs as well as the intensity and direction of selective mortality processes acting on some of these traits (i.e., pelagic larval duration, mean larval growth). Otolith analysis was paired with behavioral observations of newly settled juvenile S. partitus in the field to reveal that the relationship between size-at-settlement, early juvenile growth and survival is behaviorally-mediated. Individuals that were larger at settlement were more active (i.e., spent less time sheltered, swam farther from shelters) and grew more slowly post-settlement. Likewise, slower juvenile growth was associated with greater activity, more conspecific aggression, and faster escape swimming speeds. A six-year time series of recruitment densities revealed substantial temporal (interannual, seasonal, lunar) and spatial (by microhabitat, conspecific density) variability in recruitment which influenced the composition of recruits. For instance, larvae settling during the darkest phases of the moon were larger at settlement, but selective mortality processes during brighter periods removed more of the smallest settlers, resulting in juveniles with similar sizes-at-settlement regardless of when they arrived to the reef. Because recruitment strength and composition varied temporally, genetic markers (6 microsatellite and 1 mitochondrial loci) were used to determine if the genetic composition of monthly cohorts of settling larvae and juveniles also varies interannually, monthly, or across life stages. A lack of genetic structure suggested that S. partitus has a large effective population size and variation in ELHTs is not likely the result of successful spawning of a disproportionately small group of adults. As a whole, these results reveal processes associated with larval supply and post-settlement life that collectively shape juvenile demography.

Regulators of G-protein coupled signaling (RGS) accelerate GTP hydrolysis and consequently influence signal termination. The RGS-4 gene has recently been reported to be implicated in a wide range of neuropsychiatric disorders including schizophrenia, Alzheimer's disease and addictions.
In this study, the vervet RGS-4 gene was sequenced on a CEQ 8000 genetic analysis system (Beckman Coulter) and characterized using molecular and bioinformatic tools. The obtained vervet sequence overall showed 95.3% sequence identity with the human RGS4 gene.
Thereafter, SNPs in the region encompassing the proximal promoter, exon 1 and the first 450 bp of intron 1 were identified by direct sequencing of 8 unrelated individuals. One of the identified SNPs, +35 [A/G], was genotyped in 155 juvenile vervets previously phenotyped for personality traits, including social isolation. Although preliminary association analysis fails to attain statistical significance (p=0.074), the sample size is small. Additional genotyping of phenotypically defined individuals needs to be undertaken.

The genetic pathways influencing alcohol abuse and dependence are poorly characterized. Many critical discoveries about the interactions between ethanol-related behaviors and genetics have been made in the fruit fly Drosophila melanogaster. Coupling the statistical power of model organism studies to human association studies bolsters the analytical efficacy of these genomic approaches. A variety of behavioral assays are available for assessing behavioral responses to ethanol in Drosophila. However, we find our previously described eRING assay is influenced by the commonly used transgenic marker mini-white. We developed a Simple Sedation Assay (SSA) that is insensitive to the effects of white and mini-white. In SSAs, expression of endogenous wild-type white was not necessary for normal responses to ethanol. Neither expression nor RNAi-mediated knockdown of the transgenic mini-white influenced the effects of ethanol in flies. Critically, mini-white expression did not affect the phenotypes of flies with known alterations in ethanol sensitivity. Also, loss of function mutations in Clic show decreased sensitivity to ethanol in both eRING assays (as previously reported) and SSAs. Therefore, we explored the role of the known Clic interactors, TGF-β and ryanodine receptors. These studies were inconclusive but do not exclude the need for future work. Finally, using bioinformatic tools we constructed a mutli-species network of genes predicted to interact with Clic. Our RNAi screen against the Clic network serves as an important proof-of-concept and holds great potential for uncovering important therapeutic targets for alcohol use disorders.

Early detection of autism plays an important role in enhancing developmental outcomes for affected children. Identifying potential characteristics of the disorder evident during infancy and toddlerhood aids efforts to screen for such symptoms, which may lead to earlier and more accurate diagnoses; however, it is unclear to what extent certain factors encourage or impede early detection. Because parents are responsible for making decisions on behalf of their children based upon their perceptions of children's developmental progression, caregivers were queried in terms of their beliefs about the development of autism characteristics in their children. Participants included 393 caregivers of children with autism, Asperger's syndrome, and PDD-NOS from the U.S. and 5 other English-speaking countries who completed an online questionnaire containing both closed- and open-ended questions. Rich, descriptive information on children was provided in terms of demographic variables, comorbid diagnoses outside of the autism spectrum, the type of autism onset (congenital or regressive) children experienced, the presence of a family history of autism or other mental-health disorders, and the ages at which behavioral difference were detected for 11 early symptoms indicative of autism. Analyses were conducted with the last 4 variables within this list and with an additional variable reflecting parents' beliefs about the etiology of autism (genetic versus some external mechanism). Significant relationships existed between a variety of these variables with the exception of a family history of autism or other mental-health disorders. About half of the sample reported that their children developed autism in a congenital fashion while the remaining half, a regressive fashion. Those indicating a congenital onset reported noticing all 11 early characteristics at younger ages relative to those indicating a regressive onset; however, significant differences between groups existed for only 4 of these 11 early symptoms. Parents who indicated a congenital onset were also more likely to espouse a genetic etiology for autism relative to parents indicating a regressive onset who were more likely to attribute the disorder to some external mechanism. Type of autism onset and presence versus absence of child comorbidity independently predicted the ages at which parents detected anomalies in 7 of the 11 early characteristics. Interpretations of the findings are discussed in detail, followed by suggestions for future directions of research in this area.

Psychiatric genetics is a basic science field that has potential for practical application and effective translation. To date, translational frameworks utilized by this field have been linear (e.g., sequential) in nature, focusing on molecular genetic information. It is proposed that non-linear (e.g., socio-ecological) frameworks are a better way to immediately translate non-molecular genetic information. This dissertation explored the translation of psychiatric genetic information in two ways. First, a survey was sent to academic stakeholders to assess the state of the science regarding the translation of genetic information to the clinical care of mental health disorders. Findings from this indicate a translation-genetic competence gap whereby genetic knowledge reinforces linear frameworks and genetic competence is needed to achieve effective translation in this content area. Second, a new risk factor model for social anxiety was created that incorporated genetic, environmental, and neurophysiological risk factors (behavioral inhibition, parental bonding, emotion reactivity). Findings indicate that genetic etiology is more informative knowledge that can influence risk factor models and possibly prevention and intervention efforts for social anxiety. Overall this dissertation paves the way for examining the translational capacity of psychiatric genetics in a clinical setting. It constitutes the first examination of barriers to and a potential solution for the most effective translation of psychiatric genetic information.

This paper discusses the issue of depersonalization and the subjective need for objectification and provides a means of understanding and developing a possible solution. Through the basic observation of an overlap between Behavioral Genetics, Neuroscience, Philosophy, Psychology, Physiognomy, the visual language and the artistic practice, one can begin to take note of the affects of our environments on an individualistic level. Through creative practice and the use of the visual language, one may develop an individualistic form of therapy. In recent years we have drifted away from the science of visual language and the basic aesthetic experience. The visual language and the basic aesthetic experience allow the depersonalized individual to engage in conversation and observation through an object of the visual language to the biological inner self as person. Through this conversation one may find comfort in the acknowledgment of the biological inner self as person from the other as person in hopes to subdue the subjective need for objectification. One may also gain a better understanding of the individualistic correlation between one's environment and one's biological inner self as person.

Advancements in molecular sequencing have revealed unexpected cryptic genetic diversity and contrasting evolutionary histories within genes and between genomes of many organisms; often in disagreement with recognized taxonomy. Incongruent patterns between the mitochondrial and nuclear evolutionary history can have several plausible explanations, but widespread systematic conflict inevitably challenges our conceptions of species boundaries when there is discordance between coevolving and coinherited genomes. It is unknown to what degree mitonuclear conflict drives the process of divergence, or how ubiquitous these patterns are across the tree of life. To understand the evolutionary relevance of intergenomic discordance we must identify the conflicting patterns that exist in natural systems by generating robust estimates of the underlying species history, quantify support for alternative hypotheses of lineage formation, and describe patterns of genetic variation present in robust nuclear genomic datasets. Empirically testing correlations between mitonuclear genomic conflict and reduced gene flow at the organism level will contribute toward a better understanding of lineage boundaries and how intergenomic interactions shape the process of divergence. Mitochondrial introgression has been inferred in many salamander systems with limited perspective from nuclear sequence data. Within dusky salamanders (Desmognathus), these patterns have been observed between morphologically and geographically disparate populations. I sequenced regions throughout the nuclear genome to reconstruct species trees, performed population-level analyses testing concordance between the mitochondrial, nuclear datasets, and nuclear genes with mitochondrial functions with the expectation that coevolutionary interactions among genomes are more likely to manifest in these regions. I also estimated migration rates between populations that may have experienced historical mitochondrial introgression to evaluate phylogeographic patterns. Using these data we definitively reject species models in which genetic boundaries are based solely on mitochondrial data, favoring geographic models instead. Furthermore, analyses soundly reject current taxonomic models based on morphological characteristics, suggesting there is greater lineage diversity than is currently recognized. I also used empirical assays of pre-zygotic reproductive mating behavior within and among populations containing diverse mitochondrial lineages to test metrics of reproductive isolation, and to determine if introgression shapes the evolution of complex traits directly influencing rates of divergence. These results may explain incongruent patterns observed between the mitochondrial and nuclear data as a function of inheritance and population dynamics rather than directly functioning to suppress nuclear gene flow. This research builds upon recent studies suggesting that speciation is a highly complex and often non-bifurcating process in which introgression can have a profound and lasting signature on the nuclear evolutionary history. Mechanisms responsible for divergence with gene flow challenge evolutionary biologists to reevaluate our notions and definitions of species boundaries to accommodate seemingly conflicted genomic patterns within and between genomes.

Fighting ability is a well-known attitude in Valdostana cattle (i.e., Aosta Chestnut and Aosta Black Pied cattle), due to the strong belligerency that cows exhibit at pasture, when unfamiliar animals met and new hierarchies for the access to resource have to be established. This peculiar attitude revives during the traditional tournaments of Batailles de Reines, annually performed by cows in the Aosta Valley. Annual competition consists of 20 eliminatory tournaments and a final challenge, where only the two autochthonous breeds are allowed to take part in the battles. Using data coming from the battles, fighting ability has been investigated aiming to assess both the behavioural and genetic aspects. Four steps have been followed, aiming to look at fighting ability under different but complementary point of views and to shed light on different concerns. At first, data from 4 tournaments undertaken in 2009 have been video recorded and analysed (i.e., a total of 168 fights) in order to depict both the dynamics of agonistic interaction among cows and what factors may affect the shape and the outcome of a conflict. A suitable phenotypic score for fighting ability (i.e., Placement score) was developed in a second study using data from 6 years of battles (i.e., 2001-2006, approximately 16,000 records belonging to about 6,000 cows). This in order to build a genetic model able to investigate the variance components of fighting ability and to quantify genetic parameters. Additionally (i.e., third study), the analyses included the incidence of conspecifics in the genetic estimates of fighting ability, considering the introduction of the opponent either within the phenotype itself or directly in the model as indirect genetic effect (IGEs). As alternative analysis, the contribution of conspecifics has been retained directly into the phenotype, implementing the previous score into a Competitive Placement Score, thus applied into analogous genetic models. As further step, the effect of another force (i.e., inbreeding) and its relationship with the genetic values for fighting ability has been investigated in Aosta Chestnut and Aosta Black Pied cattle. Population data coming from the entire pedigree, as well as all available information on 9 years of battles (i.e., about 24,000 records of over 8,200 participants) permitted to assign individual inbreeding coefficients to cows. Thus, the incidence of inbreeding into genetic models for fighting ability was studied, as well the possible relation among genetic merits and inbreeding. Results obtained from this study indicate that fighting battles among cows seem to follow the typical dynamic of an escalated contest, with a cumulative assessment of the two contenders. Moreover, age, weight, and, most of all, prior experiences of the previous battles play a role in determining the outline and the intensity of the conflict. In addition, the genetic component of fighting ability results of main importance in affecting the outcome of the encounters. As well, weight, age, herd and tournament revealed as significant factor in the investigation of phenotypic variance, and, together with a direct additive and a permanent environmental, they have allowed the estimates of “non zero” genetic parameters. Heritability of fighting ability showed a level of about 0.08 when evaluated using a classical quantitative model, whereas the introduction of indirect genetic effects drove heritability estimates to levels of approximately 0.11. Moreover, including indirect genetic components showed a better general model fitting, whereas classical quantitative models taking into account of the opponent within the score exhibited the worst fitting. Reasoning on the different variance components that can be accounted into the model (i.e., either direct or indirect and due to conspecifics, as well as related to the permanent environment), models that included the opponent only as genetic effect have provided better estimates. Including the kinship as classes of inbreeding coefficient within the genetic models, heritability estimates undergo some small variations under classical quantitative models (i.e., +0.02) whereas models with IGEs did not experienced any shift due to inbreeding. However, the genetic values for fighting ability resulted as reduced in correspondence to increasing levels of inbreeding, as shown by the negative slope of the linear regression analysis performed on lineages of fighting cows with increasing inbreeding levels. As well as inbreeding shows a positive trend over years due to selection, it is interesting to note that, despite the incidence of inbreeding depression and a lack in planned selective programs, also fighting ability reveal a positive increase in mean breeding values (about 2-3% of gain/year). Thus, models including indirect genetic effects are the most appropriate tool in investigating social traits, and the study of fighting ability in Valdostana cattle may provide some interesting suggestions for the analysis of social traits in the area of animal breeding.
Le razze Valdostana Castana e Pezzata nera tradizionalmente si contraddistinguono per una spiccata belligeranza che emerge al momento del pascolo, quando gli animali provenienti da mandrie diverse si incontrano e combattono per definire nuove gerarchie sociali. Allo scopo di riproporre tale comportamento ad un pubblico più vasto, gli allevatori valdostani organizzano da secoli una caratteristica competizione che prende il nome di “Batailles de reines” e vede annualmente migliaia di esemplari contendersi il titolo di “Regina dell’anno”. Annualmente, la manifestazione consiste in 20 giornate di eliminatorie ed in un torneo finale a cui è consentito prendere parte soltanto alle bovine provenienti dalla Valle d’Aosta. I risultati dei combattimenti disputati nel corso degli anni sono divenuti materia di ricerca nel presente lavoro di tesi, allo scopo di studiare alcuni aspetti, sia genetici che comportamentali, dell’attitudine al combattimento nelle bovine valdostane. Il carattere in questione è stato studiato seguendo 4 passaggi successivi, condotti con metodologie diverse e volti a mettere in luce aspetti differenti del comportamento combattivo. La prima analisi si è focalizzata sulla dinamica delle interazioni agonistiche tra bovine combattenti, preoccupandosi di capire quali fattori possano incidere nel tipo di combattimento che viene espresso e sul suo eventuale esito. Allo scopo, sono stati considerati 168 combattimenti registrati mediante videocamera nel corso di quattro tornei svoltisi nella stagione 2009. Il dataset per le analisi è stato largamente ampliato nello studio successivo, allargato ai dati raccolti nel corso di sei anni di competizioni (dal 2001 al 2006, circa 16.000 record appartenenti a 6.000 esemplari), e volto a delineare un punteggio fenotipico (Placement Score) ben rappresentativo delle performance dei partecipanti. Tale punteggio è stato quindi utilizzato come variabile dipendente in un modello genetico volto a stimare le componenti di varianza ed i parametri genetici per l’attitudine al combattimento. Tale punteggio è stato quindi inserito come fenotipo in un modello genetico volto a stimare le componenti di varianza e i parametri genetici inerenti al carattere studiato. Un’ulteriore analisi (terzo passaggio), si è invece focalizzata sullo studio degli effetti genetici indiretti (IGEs) dovuti all’incidenza dei partner sociali nel fenotipo dell’individuo. Quale criterio di indagine, si è provveduto a confrontare modelli genetici privi dell’effetto dei conpecifici (i.e., membri della stessa specie), con modelli comprendenti invece l’avversario, alternativamente introdotto nel fenotipo (Competitive Placement Score) e nel modello genetico. Quale quarto e finale passaggio, è stato condotto uno studio di popolazione sul livello di inbreeding nelle due razze studiate, in grado di stimare coefficienti di parentela individuali. Tali coefficienti sono stati quindi inseriti nei modelli genetici (descritti in precedenza) allo scopo di determinare l’incidenza dell’inbreeding sulle stime dei parametri genetici per la combattività, nonché sul valore genetico degli individui consanguinei. Per quest’analisi si è reso disponibile un dataset più ampio, comprendente un ammontare di 24,000 record relativi ad oltre 8,200 esemplari. I risultati ottenuti a seguito di tutte le analisi condotte, dimostrano che i combattimenti tra bovine seguono le tipiche dinamiche della lotta scalata, costituita da valutazioni successive degli avversari con esibizioni ad intensità crescente. Quali risultano fattori chiave nello delineare l’esito dei conflitti e le dinamiche in cui essi si svolgono sono emersi l’età dei contendenti, il loro peso, e, soprattutto, le precedenti esperienze di combattimento. Analogamente, anche la componente genetica della combattività rivestire un ruolo significativo nell’influenzare l’esito dei conflitti. Le analisi statistiche e genetiche condotte su tale carattere hanno permesso di riconoscere come significativi fattori quali il peso, l’età, l’azienda e il torneo dell’esemplare, come pure le componenti genetica indiretta e ambientale. Le analisi condotte sui modelli quantitativi classici hanno permesso di stimare un’ereditabilità per l’attitudine al combattimento dell’8%, mentre le analisi effettuate sui modelli con effetti genetici indiretti hanno riportato valori di ereditabilità dell’11%. Confrontando le due tipologie di modelli, è emerso come l’inclusione degli effetti genetici indiretti porti a valori migliori nelle stime. Tra i vari modelli comprendenti le componenti indirette considerati negli studi, quello il più affidabile risulta includere gli effetti indiretti solo in termini di componente genetica additiva e non ambientale. L’introduzione del coefficiente di parentela nei modelli genetici, sia essi classici che comprendenti effetti indiretti, comporta delle variazioni soltanto lievi nelle stime dell’ereditabilità, dell’ordine del 2% modelli classici, e addirittura non percettibili negli altri. I valori genetici per la combattività sembrano comunque risentire negativamente dell’effetto dell’inbreeding, come suggerito dalla pendenza negativa della retta di regressione lineare ricavata analizzando genealogie di consanguinei con livelli di inbreeding crescenti. È infine interessante notare come, nonostante la mancanza di un’opera selettiva pianificata rivolta al miglioramento del carattere, l’attitudine al combattimento risulti comunque aumentare nel tempo, rivelando un incremento nei valori genetici del 2-3% annuo. Da questa, e dalle precedenti considerazioni effettuate per le precedenti analisi, è possibile concludere che l’attitudine al combattimento nella razza Valdostana può offrire al miglioramento genetico degli spunti di riflessione interessanti per l’analisi dei comportamenti e dei caratteri sociali.

Huntington’s disease is an incurable, progressive neurological disorder characterized by loss of motor control, psychiatric dysfunction, and eventual dystonia leading to death. Despite the fact that this disorder is caused by a mutation in one single gene, there is no cure. The mutant Huntingtin (mHtt) protein is expressed ubiquitously throughout the brain but frank cell death is limited to the striatum. Recent work has suggested that Rhes, Ras homolog enriched in striatum, which is selectively expressed in the striatum, may play a role in Huntington’s disease neuropathology. In vitro studies have shown Rhes to be an E3 ligase for the post-translational modification protein SUMO. Rhes increases binding of SUMO to mHtt which competes for the same binding site as Ubiquitin. SUMOylation of mHtt leads to disaggregation and cellular death, whereas ubiquitination leads to aggregation and cellular protection. In a previous study we showed that deletion of Rhes caused a decrease in the Huntington’s disease phenotype in mice. We hypothesized that mice lacking Rhes would also show increased aggregation in the striatum and this increased aggregation would correlate in a rescue of behavioral symptoms. Despite the prior in vitro and in vivo evidence, deletion of Rhes in vivo did not alter the aggregation of mHtt in the striatum of mice however deletion of Rhes still showed a rescue from the diseased phenotype. This result would indicate that deletion of Rhes alters the neurobehavioral phenotype of Huntington’s disease through a different pathway than promoting aggregation in striatal cells.

As mucopolissacaridoses (MPS) são um grupo de doenças metabólicas hereditárias causadas pela deficiência de enzimas lisossomais específicas, que causam alterações físicas e/ou comportamentais crônicas e progressivas. Um fenótipo comportamental é um padrão característico de observações motoras, cognitivas, linguísticas e sociais consistentemente associado a uma condição biológica. Tal fenótipo pode ser um transtorno mental ou outras características de comportamento não necessariamente associadas a transtornos. No caso específico das mucopolissacaridoses, embora haja diversos relatos na literatura sobre as altas taxas de ocorrência de problemas de comportamento na síndrome de Sanfilippo (MPS III), muito pouco é conhecido sobre as características comportamentais das outras entidades (MPS I, II, IV, VI e VII). Este trabalho pretendeu avaliar e descrever as alterações psiquiátricas encontradas em 22 pacientes com MPS atendidos em três serviços de genética clínica (4 MPS I, 5 MPS II, 1 MPS III, 4 MPS IV, 7 MPS VI, 1 MPS VII). As avaliações foram feitas através de instrumentos específicos, traduzidos e validados para nossa população, a saber: K-SADS PL, ATA, CARS, CGAS; e um instrumento traduzido, mas ainda sem validação brasileira: Escalas de Comportamento Adaptativo de Vineland. Os resultados mostraram que esses indivíduos apresentam altas taxas de transtornos mentais ao longo da vida, comportamento adaptativo deficitário e funcionamento global prejudicado. Além disso, observou-se um grande impacto familiar da doença, abandono escolar por falta de condições de acesso e de preparo da própria escola, grande dependência dos indivíduos avaliados e sobrecarga de um único cuidador, geralmente a mãe. Também ficou evidente o peso trazido pelo próprio tratamento, traduzido em uma recusa em aceitar novas propostas clínicas oferecidas. Concluiu-se que a população estudada é altamente vulnerável dos pontos de vista pessoal, familiar e social, sendo necessários mais estudos para seu melhor conhecimento e elaboração de programas e políticas de atendimento mais direcionados para suas necessidades
Mucopolysaccharidoses (MPS) are a group of hereditary metabolic diseases caused by deficient lysossomal enzymes, that lead to progressive physic and/or behavioral abnormalities. A behavioral phenotype is a characteristic pattern of motor, cognitive, linguistic and social observations, consistently associated to a biological condition. That phenotype may be a mental disorder or other behavioral characteristics not necessarily associated to any specific disorder. Referring to MPS, altohugh there are several descriptions of high ocurrence of behavioral problems in patients with Sanfilippo Syndrome (MPS III), the knowledge about behavioral characteristics of the other types of MPS is scarce. This work intended to analyse and describe psychiatric alterations in 22 patients with MPS from three services of medical genetics. Evaluation was made using specific instruments, translated and validated for use with brazilian population: K-SADS-PL, ATA, CARS, CGAS; and one instrument translated but not validated for brazilian population: Vineland Adaptive Behavior Scales. Results showed high lifetime prevalence of mental disorders, deficient adaptive behavior, and poor global functioning. Besides, it was observed intense familiar impact, high drop out rates from school, highly dependent individuals, and excessive burden for the caretaker. It was also evidenced the burden of the treatment itself. The conclusion was that this population is extremely vulnerable, and that it is necessary the realization of more studies for the better understanding of its specific necessitites

This thesis combines behavioral observations of African lions (Panthera leo) with genetic analyses, in an attempt to clarify causes and consequences of lion group living. The numerous complex cooperative behaviors of lions present an excellent opportunity to investigate the evolution and maintenance of group living. This thesis focuses on female group living and male dispersal patterns. Lion sociality is found to be more complex than previously thought. Short dispersal distances result in strong kinship ties among prides, creating the potential for kin selection to operate among prides. Simultaneously, some prides contained unrelated females, depriving females in such prides of inclusive fitness benefits from group living. Concurrent with short dispersal distances in both males and females, significant genetic differentiation could be detected over relatively short distances in analyses of males. Extensive behavioral observations showed that territorial behaviors were unaffected by kinship ties to intruders. Instead, favorable odds and several environmental conditions were important factors. Space use analyses showed large overlap among prides. Again, kinship did not affect degree of overlap. Conclusively, these results show that the ultimate causes of lion sociality remain elusive, but that kin selection may be less important than generally thought. Lion sociality seems to be explicable mainly in terms of direct fitness benefits, which therefore should be given more attention.

Diabetes has become a longstanding public health challenge around the world. Over the last 3 decades, the number of people with Type II diabetes (T2DM) has grown to an epidemic level in Canada. Prior research indicated African immigrants residing in Ontario, Canada experienced a 2–4 times higher prevalence of T2DM than Canadian-born individuals. The social determinants of health theoretical framework guided this study assessing the relationship of the risk factors with T2DM. A quantitative, cross-sectional design was employed using the 2007–2014 Canadian Community Health Survey data. The random sample included 1,526 African immigrants residing in Ontario, Canada. Descriptive, bivariate, and multivariate analyses were conducted. Study results indicated a lower income level, high acculturation index, and a country of origin significantly associated with T2DM in adjusted and unadjusted binary logistic regression models. Using the results of the study to create a valid and reliable acculturation measurement scale and a cultural-based design of public health programs, increase awareness, and change policies that consider the needs of the sample populations could lead to positive social change by curbing the prevalence of T2DM observed in African immigrants residing in Ontario and Canada at large.

Humans spend a third of their lives sleeping but very little is known about the physiological and genetic mechanisms controlling sleep. Increased data from sleep phenotyping studies in mouse and other species, genetic crosses, and gene expression databases can all help improve our understanding of the process. Here, we present analysis of our own sleep data from the large-scale phenotyping program at The Jackson Laboratory (JAX), to identify the best gene candidates and phenotype predictors for influencing sleep traits. The original knockout mouse project (KOMP) was a worldwide collaborative effort to produce embryonic stem (ES) cell lines with one of mouse’s 21,000 protein coding genes knocked out. The objective of KOMP2 is to phenotype as many as of these lines as feasible, with each mouse studied over a ten-week period (www.mousephenotype.org). The phenotyping for sleep behavior is done using our non-invasive Piezo system for mouse activity monitoring. Thus far, sleep behavior has been recorded in more than 6000 mice representing 343 knockout lines and nearly 2000 control mice. Control and KO mice have been compared using multivariate statistical approaches to identify genes that exhibit significant effects on sleep variables from Piezo data. Using these statistical approaches, significant genes affecting sleep have been identified. Genes affecting sleep in a specific sex and that specifically affect sleep during daytime and/or night have also been identified and reported. The KOMP2 consists of a broad-based phenotyping pipeline that consists of collection of physiological and biochemical parameters through a variety of assays. Mice enter the pipeline at 4 weeks of age and leave at 18 weeks. Currently, the IMPC (International Mouse Phenotyping Consortium) database consists of more than 33 million observations. Our final dataset prepared by extracting biological sample data for whom sleep recordings are available consists of nearly 1.5 million observations from multitude of phenotyping assays. Through big data analytics and sophisticated machine learning approaches, we have been able to identify predictor phenotypes that affect sleep in mice. The phenotypes thus identified can play a key role in developing our understanding of mechanism of sleep regulation.

La démonstration de la participation des gènes dans la formation des comportements humains est l’une des plus grandes découvertes récentes pour les sciences humaines. La nécessité de trouver une raison génétique et héréditaire comme cause des comportements humains a conduit à l’émergence d’une nouvelle branche de la génétique scientifique baptisée « Génétique du Comportement ». La recherche en génétique du comportement ne limite pas à la simple démonstration de l’importance des facteurs génétiques dans l’étude du comportement, et permet de poser la question de l’action des gènes et des facteurs environnementaux sur le comportement. Pour les sciences humaines, les sciences sociales et la psychologie, l’influence des gènes sur les activités mentales, comportementales et cérébrales de l’homme est un objet d’étude. Ainsi, depuis l’émergence de la génétique du comportement, il est devenu plus facile d’expliquer la manifestation des comportements humains et des maladies mentales. Le domaine très étendu de la génétique du comportement a engendré une multitude de préoccupations morales et sociales ainsi que juridiques. Bien que nombre de ces préoccupations ne soient pas spécifiques à la génétique du comportement, ou même à la génétique, il y a toujours de bonnes raisons d'être conscients d'eux. Les implications politiques d'une base génétique pour les comportements sont très répandues et s’étendent au-delà de la clinique dans les domaines socialement importants de l'éducation, la justice pénale, la procréation et le travail. La nouveauté et le développement considérable de ce nouveau domaine de la génétique expliquent en partie pourquoi les spécialistes de l’éthique sont peu au fait des questions éthiques et juridiques y afférant, notamment en termes de conséquences et de recherches. Cela démontre l’existence de failles profondes, tant au niveau national et international, que dans la protection des participants vulnérables aux examens et aux recherches en génétique comportementale. Le but dans cette thèse est de vérifier juridiquement les risques de discrimination et de stigmatisation, les défis juridiques et les encadrements nécessaires dans le champ d’application des recherches génétiques comportementales à l’égard du public, des droits fondamentaux des sujets concernés et des participants vulnérables ayant des maladies mentales ou une tendance aux comportements qualifiés d’ « antisociaux »
Demonstrating the involvement of genes in the formation of human behavior is one of the greatest recent discoveries in the human sciences. The need to find a genetic and hereditary reason for human behavior led to the emergence of a new branch of scientific genetics called "Behavioral Genetics". Behavioral genetic research does not limit the simple demonstration of the importance of genetic factors in the study of behavior, and allows asking this question how genes and environmental factors have an effect on behavior. Recently, in the human sciences and psychology, the influence of genes on human mental, behavioral and cerebral activities is widely studied. The extensive field of behavioral genetics has engendered a multitude of moral and social concerns as well as legal issues almost since its inception. Although many of these concerns are not the same as behavioral genetics, or even genetics, there are always good reasons to be aware of them. The political implications of a genetic basis for behaviors are widespread and extend beyond the clinic into areas that are socially important for education, criminal justice, procreation and ultimately for the upbringing of children. The novelty and considerable development of this new area of genetics partly explains why ethics specialists have the right to ignore the ethical and legal issues relating to them, particularly in terms of consequences and research. This demonstrates the existence of profound loopholes, both nationally and internationally, and in the protection of vulnerable participants in behavioral genetics testing and research. The purpose of this thesis is to legally verify the risks of discrimination and stigmatization, legal challenges and frameworks as well as the scope of behavioral genetic research with regard to the public, the fundamental rights of the subjects concerned and the vulnerable participants

Environmental conditions imposed onto organisms during certain phases of their life cycles such as embryogenesis or puberty can not only impact the organisms’ own health, but also affect subsequent generations. The underlying mechanisms causing intergenerational phenotypes are not encoded in the genome, but the result of reversible epigenetic modifications. This work investigates in a mouse model the impact of paternal nicotine exposure on the next generation regarding addictive behavior modulation, metabolic changes, and molecular mechanisms. It provides evidence that male offspring from nicotine-exposed fathers (NIC offspring) is more resistant to lethal doses of nicotine. This phenotype is gender-specific and depends on short-term environmental challenges with low doses of nicotine prior to the LD50 application. The observed survival phenotype is not restricted to nicotine as drug of abuse, but also presents itself, when NIC offspring is challenged with a cocaine LD50 after acclimatization to low doses of either nicotine or cocaine. Functionally, NIC offspring metabolizes nicotine faster than control. Mechanistically, NIC offspring livers show global up-regulation of xenobiotic processing genes (XPG), an effect that is even more pronounced in primary hepatocyte cultures. Being known targets of Constitutive Androstane Receptor (CAR) and Pregnane X Receptor (PXR), these XPGs show higher baseline expression in naïve NIC offspring livers. Nicotine’s action on the brain’s reward circuitry does not appear to be of biological significance in our model system. Taken together, paternal nicotine exposure leads to a non-specific and conditional phenotype in male NIC offspring that may provide a general survival advantage against xenobiotic challenges.

Environmental conditions imposed onto organisms during certain phases of their life cycles such as embryogenesis or puberty can not only impact the organisms’ own health, but also affect subsequent generations. The underlying mechanisms causing intergenerational phenotypes are not encoded in the genome, but the result of reversible epigenetic modifications. This work investigates in a mouse model the impact of paternal nicotine exposure on the next generation regarding addictive behavior modulation, metabolic changes, and molecular mechanisms. It provides evidence that male offspring from nicotine-exposed fathers (NIC offspring) is more resistant to lethal doses of nicotine. This phenotype is gender-specific and depends on short-term environmental challenges with low doses of nicotine prior to the LD50 application. The observed survival phenotype is not restricted to nicotine as drug of abuse, but also presents itself, when NIC offspring is challenged with a cocaine LD50 after acclimatization to low doses of either nicotine or cocaine. Functionally, NIC offspring metabolizes nicotine faster than control. Mechanistically, NIC offspring livers show global up-regulation of xenobiotic processing genes (XPG), an effect that is even more pronounced in primary hepatocyte cultures. Being known targets of Constitutive Androstane Receptor (CAR) and Pregnane X Receptor (PXR), these XPGs show higher baseline expression in naïve NIC offspring livers. Nicotine’s action on the brain’s reward circuitry does not appear to be of biological significance in our model system. Taken together, paternal nicotine exposure leads to a non-specific and conditional phenotype in male NIC offspring that may provide a general survival advantage against xenobiotic challenges.

This paper presents the Social Phobia Psychotherapy Research Network. The research program encompasses a coordinated group of studies adopting a standard protocol and an agreed-on set of standardized measures for the assessment and treatment of social phobia (SP). In the central project (study A), a multicenter randomized controlled trial, refined models of manualized cognitive-behavioral therapy and manualized short-term psychodynamic psychotherapy are compared in the treatment of SP. A sample of 512 outpatients will be randomized to either cognitive-behavioral therapy, short-term psychodynamic psychotherapy or waiting list. Assessments will be made at baseline, at the end of treatment and 6 and 12 months after the end of treatment. For quality assurance and treatment integrity, a specific project using highly elaborated measures has been established (project Q). Study A is complemented by 4 interrelated add-on projects focusing on attachment style (study B1), on cost-effectiveness (study B2), on variation in the serotonin transporter gene in SP (study C1) and on structural and functional deviations of the hippocampus and amygdala (study C2). Thus, the Social Phobia Psychotherapy Research Network program enables a highly interdisciplinary research into SP. The unique sample size achieved by the multicenter approach allows for studies of subgroups (e.g. comorbid disorders, isolated vs. generalized SP), of responders and nonresponders of each treatment approach, for generalization of results and for a sufficient power to detect differences between treatments. Psychological and biological parameters will be related to treatment outcome, and variables for differential treatment indication will be gained. Thus, the results provided by the network may have an important impact on the treatment of SP and on the development of treatment guidelines for SP
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Thesis: M. Eng., Massachusetts Institute of Technology, Department of Electrical Engineering and Computer Science, 2017.
This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.
Cataloged from student-submitted PDF version of thesis.
Includes bibliographical references (page 55).
In this work I introduce genetic programming [5] as a general technique to produce programs with arbitrary behavior. I discuss genetic programming and its application the task of symbolic regression. I introduce behavioral genetic programming [6] as an extension to genetic programming and explore various extensions to it. The codebase that I build is made sufficiently flexible to easily accommodate future adaptions to the behavioral genetic programming methodology. I test the performance of the implementation of behavioral genetic programming along with several extensions.
by Steven B. Fine.
M. Eng.

Much recent scholarship in Victorian studies has viewed sexuality as historically contingent and constructed primarily within the realm of discourse or social organization. In contrast, the following study details species-typical and universal aspects of human sexuality that must be adequately theorized if an accurate model of the ideological forces impacting Victorian sexuality is to be fashioned. After a short survey of previous scholarly projects that examine literature through the lens of biology—much of it marred by an obvious antipathy toward all attempts to discover the involvement of ideology in human behavior—this study presents a lengthy primer to the modern study of evolutionary psychology, behavioral genetics, and human sexuality. Because the use of science is still relatively rare in literary studies, the first chapters are designed both to convince the reader of the necessity of considering biology and evolution in examining human sexuality, as well as to provide the general educated scholar in our field with the basic framework of knowledge necessary to follow the remainder of the text. Chapter three follows with a detailed examination of the sources of the political resistance to biological and genetic models of human behavior within liberal arts and social science departments, and chapter four presents an evolutionary and biochemical model for the apprehension of art that locates the origins of culture within the evolutionarily-fashioned brains of individuals and attempts to recuperate the concept of aesthetic emotion and foreground the special nature of erotica in its ability to produce immediate neurochemical effects in the brains of its consumers. Finally, the study examines works of Victorian literature, especially My Secret Life, to demonstrate the deficiencies in constructionist and interactionist theories of human sexuality while detailing the new readings that emerge when one is aware of the biological basis of human mate selection mechanisms.