Behavioral Genetics Discussion Post

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