Behavioral Genetics Discussion post

Measuring Behavior

Dr. Katie Dabrowski, PT, DPT, CSCS

We measure behavior in

the field and lab

There are, of course, advantages and disadvantages for both

• We can conduct analyses under “true” environments and conditions • We can observe behaviors that give us a lot of insight into how a particular group

works • But we can’t experimentally manipulate

In the field:

• We can control things like temperature, humidity, light/dark cycle, diet, social environment, age, breeding, genetics, etc.

• But it’s hard to generalized our findings to more populations, given this control and specific testing populations

In the lab:

Behavioral Assays in

Mice and Rats

• Monitors spontaneous exploratory behavior when an animal is placed in an enclosure

• Video-recorded, and therefore allows for measurement of total activity, average speed, number of activity bouts, etc.

• Example: Mice are recorded in an enclosure with a bright and dark area, and time spent in each area is measured. Mice are nocturnal, and choosing an area of bright illumination over the dark area is a sign of boldness, whereas the opposite is interpreted as anxiety.

Open field test:

• Animals are trained to use visual cues to swim toward a hidden platform in a circular pool

• It measures spatial navigation and memory

Morris water maze:

Behavioral Assays in

Mice and Rats

• Placing a running wheel in an animal’s cage can measure spontaneous endogenous locomotor activity

Running wheel

• Measures balance by placing rodents on a slowly revolving rod – literally measure the time it takes for the rodent to fall off, as a measure of balance

• Can assess the effects of mutations on proprioception and postural control

Rotating rod

• Assesses an individual's preference for a particular substance (usually a drug) by providing an animal a choice of a container that holds the substance vs. a water control

Preference tests

Controlling experimental variation

To minimize variation, it is essential to conduct studies such that

measurements are completed at the same time of day, and under

controlled conditions of temperature, humidity, air flow, and

illumination

Behaviors of sexes should be measured separately

Diet and age should be standardized

Sexual experience of animals (virgin, pregnant, or sexually-

experienced) can also influence behaviors

Social environment should be controlled (animals in isolation

behave differently than those in crowded conditions)

Genetic background can be a variable, so in animal studies,

comparing litter mates and inbred strains can be helpful, or using

twins in human studies

Sources of variation in

behavior: Genetic Variation

• We can study genetic variation to identify genes affecting any treat • We can create variation via mutagenesis • Or we can rely on mutations that occurred spontaneously in

nature • We generally use the term mutation to refer to a lab-generated

allele, and polymorphism to refer to a naturally found change in allele

How do we determine what genes affect behavior?

Let’s take a look at types of mutant alleles

Types of mutant alleles

Remember – naturally occurring mutations are called polymorphisms; mutations are what we call what we do in labs • Single nucleotide polymorphisms (SNPs – pronounced snips): Point

mutations that are changes one nucleotide to another • Mutations can occur in both coding and non-coding regions • Most common: Substitution of a purine for another purine (A to G,

vice versa) or a pyrimidine for another pyrimidine (C to T, vice versa)

• Three types of point mutations: • Silent/synonymous mutations: Do not result in change in the

amino acid, but they may cause changes in the phenotype • Missense/non-synonymous mutations: Do result in a change in the

amino acid • Nonsense mutations: Result in premature formation of a stop

codon, therefore generating a truncated protein product – and will be called a null mutation if the protein is rendered completely dysfuncional

Types of mutant alleles

• Frameshift mutation: The pattern of DNA requires the typical triplet code of nucleotides; this type of mutation occurs when the total number of nucleotides is not a multiple of three.

• Large-scale rearrangements in chromosomal structure: • Gene duplications • Chromosomal translocations • Inversions • Large deletions

Mutation classification

• Loss of function/null mutations: When a mutation abolishes the function of the affected gene • Usually recessive • When the mutation

prevents the survival of the individual, the mutation is a lethal mutation

• Hypomorphic mutations: Mutations that don’t abolish the function of the gene altogether, but reduce the efficiency of transcription, mRNA stability, or effectiveness of the encoded protein’s function

• Hypermorphic mutations: Gain-of-function mutations, which result in a new or abnormal function of the gene