Genes and Proteins

Lecture 2

PSY391SJohn Yeomans

Why Use Genes?

• Behavior = Genes <=> Environment• Psychologists have studied environmental

effects on behavior best for a century.• Human genome project now gives us all

the genes. What an opportunity!• Most of these genes are found in lower

animals such as mice.• Behavioral effects of single genes can be

studied in mice and humans.

DNA

• 4 Bases: Cytosine and guanine, adenine and thymine.

• Deoxyribose backbones hold 2 complementary chains each with full information.

• Can separate and then self-replicate.• Hold all genetic information in higher

animals.• Human genome 3.1 billion bases (2000).

Messenger RNA

• Single chain with 4 bases, C, G, A and uracil instead of T.

• Ribose backbone.

• Transcribed from DNA in nucleus, then spliced (“edited”), then translated into proteins by ribosomes in cytoplasm.

Proteins

• Single chain of 20 amino acids.

• 1 Codon: 3 bases1 amino acid.

• Start (AUG) and stop codons.

• Genes (about 25,000) and pseudogenes.

• Folding of proteins into complex 3D structurescomplex functions.

• Trafficking of proteins into many different cell sites.

What is a Gene?

• A DNA sequence that codes for 1 protein.

• Hard to count genes. First, find start and stop codons.

• Exons and introns--Junk DNA?

• But some fragments don’t work as proteins--Pseudogenes.

• No agreement on exact number.

Gene Technology

• Cutting DNA with restriction enzymes.

• Measuring lengths with gel electrophoresis.

• Copying DNA by cloning or PCR.

• Automated sequencing by computer (Mbases per day)

• Complete genomes of hundreds of species.

Functional Studies

• Hybridization of DNA and RNA.

• Blotting to find specific chains: Southern-DNA, Northern-RNA, Western-proteins.

• In situ hybridization: Find RNA in brain.

• Immunocytochemistry: Find proteins in brain.

Chromosomes

Lecture 3

PSY391S

John Yeomans

Mutations, Chromosomes and Genetic Diseases

Lecture 3 PSY391S• Mutants

• Chromosomes

• Chromosome Disorders

• Gene Disorders

• Linkage of Genes to Diseases

• Gene Therapy and Ethics

Mutants

• Random mutations: spontaneous, or induced by chemicals (ENU) or radiation.

• Targetted mutations of single genes: transgenic--added copies; knockouts--deleted copies.

• Flies and mice used commonly.

• About 1/3 of behavioral neuroscience now studies of mutants, especially mice.

Knockout Mice

Sedivy & Joyner,1992

Chromosomes

Chromosome Bands

Chromosome Maps

• Breaks and Crossovers: Genes are linked on each chromosome by distance.

• Morgan: Use linkage to map gene distances on each chromosome--cM.

• Genome Projects: Each Ch mapped in megabases (Mb).

• Genetic diseases can be mapped by distance from markers!

HGP Map

Chromosome Disorders

• Extra Chromosome: trisomy 21 (Down’s syndrome), trisomy 18.

• Deletions: 5p- (Cri du chat), 7q- (Williams’)

• Breaks: Fragile X

• Most large chromosome additions and deletions are lethal and lead to spontaneous abortions.

Neurogenetic Disorders

• Huntington’s: extra CAG repeats on 4p.

• Fragile X: extra CGG on X.

• Alzheimer’s: point mutations on Ch1, 21 etc.

• Recessive and Dominant

• Disease Gene Searches: Chromosome link, to gene link, to base change links.

• Animal Models of Disease.

Gene Therapy and Ethics

• Spontaneous Abortions

• Amniocentesis and Counselling

• Life Planning

• Adult Gene Therapy?

• Future of Species?