Handbook of Psychology, Behavioral Neuroscience

Irving B. Weiner, Randy J. Nelson, Sheri Mizumori

• Publisher: Wiley
• Year: 2012
• Print ISBN: 9780470890592
• eBook ISBN: 9781118282021
• Edition: 2
• Topic: Psychology
• Subtopic: History & Theory in Psychology
• Index: Psychology

Psychology is of interest to academics from many fields, as well as to the thousands of academic and clinical psychologists and general public who can't help but be interested in learning more about why humans think and behave as they do. This award-winning twelve-volume reference covers every aspect of the ever-fascinating discipline of psychology and represents the most current knowledge in the field. This ten-year revision now covers discoveries based in neuroscience, clinical psychology's new interest in evidence-based practice and mindfulness, and new findings in social, developmental, and forensic psychology.

Chapter 1

Behavioral Genetics

Stephen C. Maxson

Introduction

Subjects

Genome Projects

Methods

Genetics and Behavioral Taxonomy

Genetics and Biological Mechanisms of Behavior

Genes, Environment, and Behavioral Development

Future Directions

References

Introduction

Behavioral genetics is a science with dual origins and goals. The study of behavioral genetics that originated in psychology is primarily concerned with the causes of individual variation. The Behavior Genetics Association and its journal, Behavior Genetics, have this as their focus. The emphasis is mainly on the genetics of human behavior and mind. Nonhuman animal, mainly rodent, studies of genes and behavior are of interest for their contribution to human behavior genetics. Behavioral genetics that originated in biology is primarily concerned with genetics as a tool to study behavior. The International Behavioral and Neural Genetics Society and its journal, Genes, Brain, and Behavior, have this as their focus. Here the genetics of behavior and mind of a wide range of animals as well as humans are of interest in themselves and in relation to each other. Regardless, evolution is an essential context for both subfields of behavioral genetics.

Both subfields of behavioral genetics are well-established. The long history of behavior genetics and its many contributions to psychology and biology have been reviewed by Maxson (2007), Lohelin (2009), and Dewsbury (2009). The literature of both subfields of behavioral genetics is now so large that even multiauthor texts (e.g., Plomin, DeFries, McClearn, & McGuffin, 2008) or monographs with multiauthor articles (e.g., Jones & Mormede, 2007; Kim, 2009) do not cover the vast range of methods and findings across many species. Thus, it is impossible to do so in this short review. Rather, the coverage in this chapter must be selective. The topics to be considered derive from the seminal paper of Ginsburg (1958), Genetics as a Tool in the Study of Behavior. In this paper, he cogently argued that in the context of evolution, genetics is a way of defining natural units of behavior, of analyzing the underlying biological mechanisms of behavior, and of studying the effects of environmental and experiential variables on behavior. He illustrated each of these with findings from his research programs on mouse seizures and aggression and from canid reproduction and sociality. This paper was published 5 years after those on Watson and Crick's model of the structure of DNA and its implications for gene replication, mutation, and function. This was also many years before Sydney Brenner (1973) and Seymour Benzer (1971) made similar proposals for genetic studies of behavior respectively in Caenorhabditis elegans and in Drosophila melanogaster.

Subjects

The main animal subjects for behavior genetics are roundworms (C. elegans), fruit flies, zebrafish, mice, rats, canids, primates, and humans. This review will focus on mice, other rodents, primates, and humans. The interested reader may want to consult these reviews, articles, or books on the genetics of behaviors in C. elegans (Jansen & Segalat, 2007), fruit flies (Belay & Sokolowski, 2007; Bellen, Tong, & Isuda, 2010; Comas, Guillame, & Preat, 2007; Dickson, 2008; Vosshall, 2007), honeybees (Smith, Toth, Suarez, & Robinson, 2008), zebrafish (Norton & Bally-Cuif, 2010; Rinkwitz, Mourrain, & Becker, 2011), rats (Brush & Driscoll, 2002, Driscoll, Fernandez-Teruel, Corda, Giorgi, & Stelmer, 2009), canids (Scott & Fuller, 1965; Wayne & Ostrander, 2007; Parker, Shearin, & Ostrander, 2010), and primates (Lesch, 2003; Weiss & King, 2007). The interested readers may also want to consider a review of selective breeding and behavior studies mostly in fruit flies, mice, and rats (Greenspan, 2003), the chapter on other creatures in the text by Ehrman & Parsons (1981), and a review comparing genetic issues and findings for animal and human behaviors (Kendler & Greenspan, 2006).

Genome Projects

An individual's nuclear genome consists of the DNA found in all the chromosomes in the nucleus of its cells. There is one molecule of DNA for each chromosome. The goal of a genome project is to determine the sequence of the nucleotide bases—adenine, cytosine, guanine, or thymine (A, C, G, or T)—of the nuclear genome of one or more individuals of the species. After the entire sequence is known for a species, it is possible to estimate the number of protein-coding genes in its genome. Also, the amino acid sequence in each protein can be deduced from the coding nucleotide triplets in the gene's structural region. Other DNA sequences of a gene bind proteins known as transcription factors. These factors and sequences together are involved in controlling when and where a gene is transcribed as RNA (ribonucleic acid). A small fraction of the transcribed RNA is processed into a messenger RNA (mRNA), and the mRNA is then translated into the sequences of amino acids in its protein. Other transcribed RNA may regulate gene transcription or mRNA translation. There is also DNA in the mitochondria; this DNA codes amino-acid sequences of some of the proteins involved in energy metabolism. This DNA has been sequenced in many organisms.

The DNA sequence of the human genome was initially published in 2001. To date, the DNA sequence of the following animal species by common names have also been partially or wholly published: hydra, round worms (two species), sea urchin, sea hare, fruit fly (two species), flour beetle, honeybee, wasp, aphid, mosquitoes, zebrafish, stickleback fish, green puffer fish, Japanese puffer fish, frog (two species), chicken, zebra finch, duckbill platypus, opossum, mouse, rat, cat, dog, horse, sheep, cattle, pig, giant panda, marmoset, macaque monkey, chimpanzee, and orangutan (www.genomenewsnetwork.org/ resources/ sequenced_genomes/ genome_guide_p1.shtml). In progress are programs for some degree of DNA sequencing for 5,000 insect species (Robinson et al., 2011) and 10,000 vertebrate species (Hausler, O'Brien, & Ryder, 2009). The complete or partial DNA sequence of these species has facilitated or will facilitate the genetic analysis of behaviors in these species and a comparative genetics of behaviors across these species. A comparative analysis of genetics of behavior will eventually be firmly based on findings for the effects of homologous genes across species as considered by Robinson, Fernals, & Clayton (2008) for social behavior and by Maxson (2009) for aggression.

Methods

There are essentially four approaches to finding and studying genes with effects on behavior. The first is based on linkage or association of naturally occurring genetic variants with behavior. The second is based on effects on behavior of induced genetic mutations. The third is based on effects on behavior of reducing or blocking the translation of a gene's mRNA into its protein. The fourth is based on behavioral correlations with transcription into mRNA of one or more genes.

Natural Genetic Variants and Behavior

There are two approaches to finding and studying effects of naturally occurring genetic variants on behavior. These two approaches can be used with both animals and humans.

The first maps quantitative trait loci (QTLs) with behavioral effects to regions of specific chromosomes. Within the QTL are one or more genes with effects on behavioral variation. This approach depends on well- spaced DNA markers across all the chromosomes, such as single nucleotide polymorphisms (SNPs). Once a replicable QTL is identified, the next step is to find the DNA variants of the gene or genes underlying the QTL. Some recent reviews on QTLs and behavior are: Cherny (2009), Molson (2007), MacKay, Stone, and Ayroles (2009), and Haworth and Plomin (2010). QTLs are considered further in the section on genetics and behavioral taxonomy.

The second correlates DNA sequence variants in regulatory or coding or noncoding regions of a gene with behavior. This approach depends on knowing some, if not all, of the DNA sequence of the gene and identifying DNA sequence variants of the gene. Some recent reviews on this approach include: Caspi and Moffit (2006) for genotype by environment interactions, Epstein and Israel (2009) for human personality, and Rhee and Waldman (2009) for conduct and antisocial personality disorders. DNA variants of known genes are considered further in the section on Genetics and Behavioral Development.

Gene Mutations and Behavior

There are two approaches to induced mutations in single genes with large effects on behavior in animals but not humans.

In the first, chemical mutagens are used to cause DNA changes at random across the genome. Often the mutations are in single base pairs. They may be in regulatory or coding or noncoding regions of the gene. Mutations of a gene's coding region can cause the gene's protein to be nonfunctional, to decrease its function or increase its function. Some reviews on this approach for mice are Goldowitz et al. (2004), Godinho and Nolan (2006), van Boxtel and Cuppen (2011), and, for rats, van Boxtel and Cuppen (2010). This approach has the potential to identify all the genetic variants with effects on a behavior of a species.

In the second, the coding region of specific genes is targeted for a mutation that renders the gene's protein inactive. These are sometimes referred to as knockout mutations. A gold standard for confirming the effect of a gene mutation on behavior is to replace the mutated gene with a functional copy of it and to assess whether or not this rescues the behavioral effects of the knockout mutation. These functional replacements are sometimes referred to as transgenes. A combination of a knockout mutant and temporal or tissue specific activation of its transgene can be used to identify when and where a gene has its initial effects. For mice, this knockout approach is reviewed by Crawley (2007). For rats, a knockout approach is reviewed by Jacob, Lazar, Dwinell, Moreno, and Geurts (2010). Also, knockout approaches useable with many other animals are reviewed by Remy, Tesson, Menoret, Usal, Scharenberg, and Anegon (2010). Knockout mutants are considered further in the section Genetics and Biological Mechanisms of Behavior.

Translational Knockdowns and Behavior

The effect of a gene's protein on brain and behavior can also be assessed by attenuating or blocking the translation of its messenger RNA into its protein. There are two approaches for doing this.

The first approach involves antisense RNA. DNA has two strands with complementary base pairing. One strand is transcribed as sense mRNA. This mRNA is translated into the amino-acid sequence of the gene's protein. Transcripts from the other DNA strand are antisense mRNA. The base pair sequence of the antisense mRNA is complementary to the sense mRNA. If both DNA strands are transcribed, then the sense and antisense mRNA can hybridize into a double stranded DNA that cannot be translated. The sense strand of mRNA is usually the only transcript from a gene's DNA. However, transgenes with transcription of antisense mRNA can be inserted into genomes or brains of some animals and behavioral effects assessed. An application of this approach is considered further in the section on genetics and biological mechanisms of behavior.

The second approach for blocking translation is RNAi or interference RNA. RNAi are short sequences of RNA (about 22 bp). When combined with specific proteins, they can degrade a gene's mRNA or attenuate or block a gene's mRNA translation into its protein (Mattick, 2004; Sandy, Ventura, & Jacks, 2005). For mice, this approach is reviewed by Kuhn, Streif, and Wurst (2007) and Delic et al. (2008), and for rats, it is considered by Petit and Thiam (2010).

Gene Expression Correlates With Behavior

This approach correlates quantitative variation in mRNA transcription in brain or brain regions of one or many genes across variation in genotype or development or phenotype. mRNA levels are assessed postmortem. The level of more than one mRNA can be assessed with RNA microarrays (Johnson, Edwards, Shoemaker, & Schadt, 2005). RNA microarrays have been used to detect gene expression associated with psychopathologies in humans (Konradi, 2005), and gene expression differences between male and female brains of songbirds (Naurin, Hansson, Hasselquist, Kim, & Bensch, 2011). RNA microarrays and behavior are considered further in the section on genetics and biological mechanisms of behavior.

Genetics and Behavioral Taxonomy

A genetic variant can have effects on multiple traits. Such multiple effects of a genetic variant are known as pleiotropy. For example, there are pleitropic effects in homozygotes of the sickle-cell variant of the hemoglobin beta gene on mental function, heart failure, rheumatism, abdominal pain, and enlarged spleen. Such pleiotropic effects of genes are the fundamental basis for using genetics to identify natural units of behavior. This is exemplified for four complex behaviors: mouse aggression, mouse emotionality, mouse cognition, and human psychopathology.

Male Mouse Aggression

Five aspects of mouse aggression taxonomy will be considered. The first is unique and common genetic effects on offense and defense types of aggression. The second is unique and common genetic effects on two aspects of offense. The third is genetic correlations for measures of offense. The fourth is the genetic relationship of coping strategies and aggression. The fifth concerns the distinction between adaptive aggression and maladaptive violence.

Offense and Defense

Offense and defense aggression differ in motor patterns and in attack target (Maxson, 2009). Two studies have assessed the effect of the same gene on offense and defense. Male mice with functional and nonfunctional monoamine oxidase A (MAOA) differ in measures of offense but not defense (Chen et al., 2007) whereas male mice with functional and nonfunctional alpha calcium/calmodulin kinase II (alpha CamK II) differ in measures of both offense and defense (Chen, Rainnie, Greene, & Tonegawa, 1994). Also, overexpression ...

Table of contents

• Cover
• Title Page
• Copyright
• Dedication
• Editorial Board
• Contributors
• Volume Preface
• Chapter 1: Behavioral Genetics
• Chapter 2: Evolutionary Psychology
• Chapter 3: Comparative Vision
• Chapter 4: Visual Processing in the Primate Brain
• Chapter 5: Comparative Audition
• Chapter 6: Auditory Processing in Primate Brains
• Chapter 7: Comparative Locomotor Systems
• Chapter 8: Neural Mechanisms of Tactile Perception
• Chapter 9: The Biopsychology of Pain
• Chapter 10: Taste and Olfaction
• Chapter 11: Food and Fluid Intake
• Chapter 12: Sexual Behavior
• Chapter 13: Sleep and Biological Rhythms
• Chapter 14: Motivational Systems: Rewards and Incentive Value
• Chapter 15: Emotion
• Chapter 16: Stress, Coping, and Immune Function
• Chapter 17: Environmental Influences on Development of the Nervous System
• Chapter 18: Comparative Cognition
• Chapter 19: Biological Models of Associative Learning
• Chapter 20: Memory Systems
• Chapter 21: Social Relationships, Social Cognition, and the Evolution of Mind in Primates
• Chapter 22: The Neural Basis of Language Faculties
• Chapter 23: Neurally Inspired Models of Psychological Processes
• Chapter 24: Normal Neurocognitive Aging
• Author Index
• Subject Index