8/09/04

Were all up in the fishbowl.
Some crazy Behavioral Neurogenetics. 

----------------------------------------------------------------------------

Maristic Traits are traits you can count easily.

Like number of hairs. 

INbred strains of rats mice etc... are a good way to study genome variation.

Micro environmental variation etc...

There is a difference between the quadruplet armadillos and the inbred mice.

Its that the armadillos aren't inbred. This is a natural occurence.

All of mouse genetics is done with inbred strains.

You must focus on one thing at a time.
- When you juggle different variables things are confounded greatly.

These studies have lots of power but low generality.

If you take an inbred mouse A and inbred mouse B and mate them 
they no longer become inbred. They become an F1

They are called isogenic.


Congenic strains...

Where a normal strain has had targeted gene material removed and desired 
gene material inserted (through clever breeding etc..) Having a host strain
and knockouts.

Introgretion - this is the process of changing the target area. (Inter-
locking the desired gene strain.

Pennsylvania State University is located in the happy valey.


FUNDAMENTAL QUESTIONS ADRESSED-
Is behavior inherited?

Does Behavior evolve?


FUNDAMENTAL CONCEPTS

Phenotypes - How defined

Genotypes - how defined
- The one you're born with
- THe one you're working with at this particular moment

Environment
- Internal 
- External

Causality - How ascribed
- P = G + E
- P = G + E + (GxE)

The Central Dogma

Single genes vs. multiple genes

The Fit materials
- Human
- Animal

Phenotype = any measureable characteristic of an individual.

The more basic, the more amenable to genetic analysis
- Must be reliable in the strictest sense
  - G construct for general intelligence. Agression, intelligence, score
    on a particuluar part of an intelligent test.

- Validity can be elusive.
  - Cairns' agressive mice. It is agression or reactivity?

Phenotype can be a genotype.


GENOTYPES
- The one you're born with
- The one that is operating at a particular moment (Momentary effective
  genotype, McClearn)
- The ones that can be manipulated.

ENVIRONMENT
-Broadly defined
- Ambient conditions
- Developmental conditions
- Social conditions
- Internal mileu
  -  Disease drugs and hormones.

- Often defined as absence of genetic effect - definition by what is absent.

Causality
- Simplest
  P= G + E - additive model
- But, not all genotypes (genes) work the same in different environments -
  thus:
  - P= G + E + (GxE)


Simple DOGMA - Cell Behavior
Retro viruses can be dangerous to DOGMA.

In regards to the inbred strains they are predominantly the same, however
there are certain things that vary from subjet to subject.

Conditions attributable to single genes
- Follow Mendel's Law of segregation.
- May be recessive or dominant.
- Relatively uncommon in population.

Historical Perspectives
- Gregor Mendel - Gave us the basic tools for quantitative genetic analysis.


Archibald Garrod (1857 - 1936) Worked heavily on pharmacogenetics.

PKU is based on 4 mutations of Pah located on Chromosome 12


Environmental COntrol of the Phenotype
- Diet - most direct way to show how non genetic interventions can modify
an otherwise determined genetic behavior.

Huntington's Disease as Example of Dominant Genetic Condition

History-
- Functional Psychologists seized upon the evolution and described fitness in
    terms of biologically determined behaviors - I.E. Insects
- Ethologists also began to look at some behaviors as being primarily 
    biologically determined.
- THe revolt by american behavioral psychologists, notable J.B. watson
- Behavior Genetics is still looked upon with suspicion.

Philosophical Perspectives

- Genetic determinists. All behavior is largley influenced by genes - more 
  so than environment. 
- Interactionism. recognizes interaction between environment and gene 
  factors.

Behavioral Neurogenetics: A new way of looking at brain -behavior functions

- how much variation is ther in my phenotype:
   I.E. what causes individual differences

- What are possible sources of Variation?
 - Environment
 - Genetic
 - GE interaction

Subjects of study?

FIT MATERIALS (human study)
- Families
- Twins
  - Homo and Hetero zygous.

Are we analyzing single genes or multiple genes and their interaction?

Recombinant Strains (strains made of combinations of pieces of different 
strains) is very helpful for study.

- They are simple, 2 allele model
- Correlations exist and can be studies with independent and dependent
  variables.


Genetic correlations exist between alcohol acceptance and regional 
D1 receptor densities.

RI mice... Recombinant Inbred Mice... very good for study.

Knock outs are when certain genes are "knocked out" to study the effect of 
that gene.

- Forward genetics starts with phenotype and then works toward the genome
  to indentify the genes.
- Reverse Genetics starts with the genome and works the other way.

Ex: Knockout = reverse
    Selective Breeding = Forward

Single gene engineering helps identify how discre        ies work.