Diving into the gene pool: Chromosomes, genes and DNA DNA is the stuff that genes are made of DNA contains 4 letters: A, T, G, C All genes are made of DNA, but not all DNA is in genes!

Diving into the gene pool: Chromosomes, genes and DNA The entire DNA content of an organism is the genome. The DNA is partitioned and packaged into structures called chromosomes. Humans have 46 chromosomes (23 pairs).

Diving into the gene pool: Chromosomes, genes and DNA gene A gene C gene B Genes are information carriers! They encode the instructions to make a protein. Proteins carry out the actual work of the cells.

Diving into the gene pool: From Genes to Proteins DNA contains four letters: A T G C Within a gene, these four letters are grouped into three letter “words”. Each word codes for an amino acid (the units that make up proteins). The combination of three letter words codes for the sequence of a protein. DNA ATG - CAT - AAA Methionine - Histidine - Lysine Protein

Diving into the gene pool: The Central Dogma DNA RNA Protein Why a middle man?

Diving into the gene pool: The Central Dogma gene A DNA RNA Protein * In every cell * Only turned “on” where needed! * Protein is made in the cells where it functions – not everywhere!

The Genome: What all is in there? 6 billion ‘letters’: 2-5 % protein coding genes 25% non protein coding genes 50%+ repeated sequences Protein coding genes Human: 20,000-25,000 Mouse: 25,000 Fly: 13,000 Yeast: 6,100 Mustard weed: 25,700

The Genome: What all is in there? Nature 409: 860-921

The Genome: What all is in there? Humans share… ….99% of chimp genes ….90% of mouse genes ….61% of fly genes ….43% of worm genes ….46% of yeast genes * So what makes us different? * more proteins/gene: ~22,000 genes but ~34,000 proteins Expansion of gene families The ways proteins interact and talk to one another

The Genome: What all is in there? Regulatory sequences gene A general “on” signal turn me off in the brain turn me on high in the heart! general “off” signal

The Genome: What all is in there? Non-protein-coding RNA’s some RNA’s are active and can function in the cell on their own some RNA’s are incorporated into protein complexes to function * The main functions of non-coding RNA’s are in protein production and regulation of gene expression

The Genome: What all is in there? Repeat sequences What is typically known as ‘junk DNA’ Why there? What does it do? Repeated sequences shape the genome Can increase the size of the genome Often involved in chromosome translocations Are sometimes responsible for human disease Repeated sequences can be useful for understanding genome evolution, for tracking disease genes, and for forensic science (genetic fingerprinting)

The Genome: What all is in there? Variation Single Nucleotide Polymorphisms (SNPs) ~1 SNP per 1300-1500 letters = 3 million differences between two genomes; we are still 99.9% the same!

The Genome: What all is in there? Variation Most SNP variation is outside genes Within a gene, a SNP can have one of two effects AAG Lysine AAA Lysine AAC Asparagine

The Genome: What all is in there? Variation: the ApoE example ApoE gene contains 2 SNP’s = 3 alleles Protein letter: 112 158 E2 Cysteine Cysteine E3 Cysteine Arginine E4 Arginine Arginine E4/E4 genotype: greater chance for developing Alzeheimer’s E2/E2 genotype: “protected” from getting Alzeheimer’s

Navagating the Genome UCSC Genome browser: genome.ucsc.edu/cgi-bin/hgGateway Ensemble Genome browser: www.ensembl.org/Homo_sapiens Online Mendelian Inheritance in Man: http://www3.ncbi.nlm.nih.gov (OMIM)