Genes and Proteins

1. Genes and Proteins Lecture 2 PSY391S John Yeomans

2. 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.

3. 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).

5. 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.

7. Proteins • Single chain of 20 amino acids. • 1 Codon: 3 bases1 amino acid. • Start (AUG) and stop codons. • Genes (about 25,000) and pseudogenes. • Folding of proteins into complex 3D structurescomplex functions. • Trafficking of proteins into many different cell sites.

8. 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.

9. 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.

11. 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.

16. Chromosomes Lecture 3 PSY391S John Yeomans

17. Mutations, Chromosomes and Genetic DiseasesLecture 3 PSY391S • Mutants • Chromosomes • Chromosome Disorders • Gene Disorders • Linkage of Genes to Diseases • Gene Therapy and Ethics

18. 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.

19. Knockout Mice Sedivy & Joyner, 1992

20. Chromosomes

21. Chromosome Bands

22. 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!

23. HGP Map

24. 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.

25. 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.

26. Gene Therapy and Ethics • Spontaneous Abortions • Amniocentesis and Counselling • Life Planning • Adult Gene Therapy? • Future of Species?