Genomics The study of entire genomes Some sample sizes [[Phi]]X 174 (first complete sequence) 5,000 bp Yeast ch. 3 (first seq. ch.) 350,000 bp E. coli genome 4.6 x 106 bp largest yeast chromosome 1.5 x 106 bp entire yeast genome 12 x 106 bp smallest human chromosome (Y) 50 x 106 bp largest human chromosome (1) 250 x 106 bp entire human genome 399,000 pages of text 536 1.4 Mb floppies >1 CD 3.3 x 109 bp Now have the complete sequence of 19 different organisms (4 archaebacterium, 13 eubacteria, and 2 eukaryotes) The first complete sequence was for Haemolphilus influenzae (a gram negative bacteria) 1,830 Kb; 1,743 genes - 40% of unknown function Smallest is Mycoplasma genitalium (a gram positive bacteria) 580 Kb; 482 genes; 470 coding sequences - 88% of genome, average size=1Kb, 96 genes with no known match in other species comparison of the two genomes suggests that the minimal prokaryotic organism would need 250 genes minimal cellular organism would need 125 genes (use an RNA genome and eliminate all duplicated genes) An archaebacterium, Methanococcus jannaschii 1,700 Kb; 1,738 protein coding genes, 62% with no known function metabolism genes are prokaryotic like, transcription, translation, and replication genes are eukaryotic The first eukaryote sequenced, Saccharomyces cerevisiae 12,068 Kb in 16 different chromosomes 5,885 potential genes (6,275 ORFs), 70% of genome 140 rRNA genes, 40 small nuclear RNA genes, 275 tRNA genes and 52 transposable elements (Ty1 and Ty2) many of the differences between homologous chromosomes are due to transpostions events many duplicated regions (with small differences - cluster homology regions) S. cerevisiae Proteome the total of all of the proteins 50% can be classified by homology with known genes, 1000 already had known functions (out of 5,885) 11% are genes for metabolism, 7% for transcription, 6% translation, down to 200 different transcription factors The first multicellular eukaryote to be sequenced was C. elegans (a round worm), finished Dec., 1998 A model organism for development studies 659 somatic cells with a compete description of embryonic history 97 million bp genome 19,099 genes 25% in operons (oops!) 42% match genes in other organisms than nematodes Another 34% match other nematode genes half have no known function Can now study function by reversing classical genetics; instead of finding a mutant phenotype and working back to the gene, start with the gene, mutate it (knock-outs) and look for the altered phenotype Human Genetic Diseases Enzyme defiencies PKU 1/10,000 Albinism 1/17,000 Lesh-Nyhan Tay Sachs (only common in Ashkenazi Jews) Other (developmental, neurological, regulatory, transport, etc.) Cystic Fibrosis Cancer genes Fragile X - most common form of inherited mental retardation 1/1500 in males, 1/2500 in females caused by expansion of a 3 bp repeat in FMR-1 (CGG) normal ind. have 6-54 repeats carrier females have 50-200 repeats 200-1300 repeats in affected individuals if repeat gets larger than 50 - a very high mutation rate Human Genome Project Goals Complete a detailed human genetic map 2 Mb map 3,000 markers (RFLP's, VNTR's, microsatellites,etc.) complete a physical map 0.1 Mb a complete restriction map Aquire the genome as clones 5 kb an ordered contig map Determine the complete sequence 1 bp at $1-2/base will cost app. 3 billion dollars find all genes and determine their function [ Biol 207 ] [ Bell ] [ CSU Chico ] [ Library ] This document is maintained by: Jeff Bell Last Update: Monday, May 10, 1999