Johnson - The Living World: 3rd Ed. - All Rights Reserved - McGraw Hill Companies Genomics Chapter 10 Copyright © McGraw-Hill Companies Permission required for reproduction or display

Johnson - The Living World: 3rd Ed. - All Rights Reserved - McGraw Hill Companies Outline Introduction to Genomics Human Genome Project  Genomic Strategies  Human Genome Characteristics Genome Variation Gene Microarrays Functional Genomics Proteomics

Johnson - The Living World: 3rd Ed. - All Rights Reserved - McGraw Hill Companies Genomics Genomics is a field of biology concerned with comparing the entire DNA content of different organisms.  Genome - Full compliment of genetic information of an organism. - Gene marked by a “start” and a “stop” codon.  Open Reading Frame

Johnson - The Living World: 3rd Ed. - All Rights Reserved - McGraw Hill Companies Genomic Time Line First free-living organism was the bacterium Haemophilus influenzae sequenced in  1,830,137 base pairs First eukaryotic genome was baker’s yeast Saccharomyces cerevisiae.  13,000,000 base pairs First animal was nematode C. elegans (1998).  100,000,000 base pairs

Johnson - The Living World: 3rd Ed. - All Rights Reserved - McGraw Hill Companies

Human Genome Project 1990 American geneticists embarked on attempt to map and sequence entire human genome (3.2 billion base pairs).  DNA fragment of unknown sequence is amplified, mixed with a primer and supply of bases, and four different chain- terminating tags. - After heated, mixture will contain series of fragments of different lengths.

Johnson - The Living World: 3rd Ed. - All Rights Reserved - McGraw Hill Companies Human Genome Project Fragments separated according to size by gel electrophoresis.  Radioactively labeled and visualized on x- ray film, and sequences read by humans, or automated systems.

Johnson - The Living World: 3rd Ed. - All Rights Reserved - McGraw Hill Companies Genomic Strategies Original plan for Human Genome Project was systematic and conservative using detailed maps of each chromosome and then cloning fragments into bacterial plasmids. May 1998, Craig Venter proposed shotgun sequencing which skipped the mapping step and chopped the entire human genome.  Both research groups finished in June 2000.

Johnson - The Living World: 3rd Ed. - All Rights Reserved - McGraw Hill Companies Human Genome Characteristics Geography  30, ,000 genes - Fragmented into exons and introns. - Not distributed evenly over the genome. - Chromosome size is not a clear indication of number of genes.

Johnson - The Living World: 3rd Ed. - All Rights Reserved - McGraw Hill Companies Human Genome Characteristics DNA Coding For Proteins  Four different classes of protein-encoding genes found in the human genome. - Single Copy Genes - Segmental Duplications - Multigene Families - Tandem Clusters

Johnson - The Living World: 3rd Ed. - All Rights Reserved - McGraw Hill Companies Human Genome Characteristics Noncoding DNA  (1-1.5% of human genome is coding DNA). - Four Major sorts of noncoding DNA:  Noncoding DNA with genes  Structural DNA  Repeated Sequences  Transposable Elements

Johnson - The Living World: 3rd Ed. - All Rights Reserved - McGraw Hill Companies Genome Variation 83% of Drosophila genes match those of other species. Humans have only 300 genes which have no counterpart in the mouse genome. Single Nucleotide Polymorphisms (SNP’s)  Variations in single base pairs million distributed in human genome.  Have low mutation rate thus are excellent markers of human history.

Johnson - The Living World: 3rd Ed. - All Rights Reserved - McGraw Hill Companies Screening With SNP’s

Johnson - The Living World: 3rd Ed. - All Rights Reserved - McGraw Hill Companies Genome Variation Genomic Exchanges Between Species  Humans have several hundred genes similar to those of bacteria. Evolution of Development  About two dozen conserved gene families regulate development in animals. - Some predate origins of animals. Genome Rearrangements  Genome duplication common in the evolution of plants (change in ploidy level).

Johnson - The Living World: 3rd Ed. - All Rights Reserved - McGraw Hill Companies Gene Microarrays Gene microarray is a glass square smaller than a postage stamp, covered with millions of DNA strands.  Scanning beam moves over each biochip spot, commanding the addition of a base to growing strands of DNA. - When the entire chip has been scanned, each strand has been lengthened one nucleotide unit.  Repeats until unambiguous identification is possible.

Johnson - The Living World: 3rd Ed. - All Rights Reserved - McGraw Hill Companies Gene Microarrays Using Microarray Chips to Screen for Cancer  Ideal method of differentiating between different kinds of cancer is comparing mutations that led to the cancer. Personal Privacy Issues  After reading a biochip, genes that might affect an individual’s health, behavior, and future potential are all available for scrutiny.

Johnson - The Living World: 3rd Ed. - All Rights Reserved - McGraw Hill Companies Biochips and Cancer Screening

Johnson - The Living World: 3rd Ed. - All Rights Reserved - McGraw Hill Companies Functional Genomics Functional genomics is the identification of the function of genes in a genome.  Annotate (label) stretch of DNA according to function. - Experiments are necessary to demonstrate inferences are accurate.  Often put a gene into a different species and see what it does.

Johnson - The Living World: 3rd Ed. - All Rights Reserved - McGraw Hill Companies Proteomics Bioinformatics  Utilizing molecular genetics and powerful computational analysis to predict what sort of protein a particular sequence encodes. Proteomics  Cataloging and analyzing every protein in the human body. - Protein arrays are being developed to study all an organism’s proteins.

Johnson - The Living World: 3rd Ed. - All Rights Reserved - McGraw Hill Companies Review Introduction to Genomics Human Genome Project  Genomic Strategies  Human Genome Characteristics Genome Variation Gene Microarrays Functional Genomics Proteomics

Johnson - The Living World: 3rd Ed. - All Rights Reserved - McGraw Hill Companies Copyright © McGraw-Hill Companies Permission required for reproduction or display