1. Bailee Ludwig Quality Management

2. Before we get started…. ….Let’s see what you know about Genomics

3.  You may have heard that DNA is the blueprint for life…but what does that mean exactly?  Essentially…  DNA (Genes)  Protein  Cells  People That seems simple enough, right? Unfortunately it’s a little more complicated than that. Let’s start at the beginning…

4.  DNA =Deoxyribonucleic Acid  A helical molecule comprised of 2 polymer strands (each of which is comprised of a sequence of four nucleotides (bases) )  The Four Base Pairs  2 Purines  Adenine (A)  Guanine (G)  2 Pyrimidines  Thymine (T)  Cytosine (C)

5. Adenine (A) pairs with Thymine (T) Guanine (G) pairs with Cytosine (C)

6. Hydrogen Bonds

7. Sugar – Phosphate “Backbone” Nucleotide “Bases”

8.  A DNA sequence can be either single-stranded or double-stranded  DNA sequences have an orientation: from 5’ to 3’ or from 3’ to 5’ (chemical conventions)

9.  RNA = Ribonucleic Acid  A single-stranded molecule  It is comprised of four nucleotides  A, C, G, and U (Uracil)  Different types of RNAs  Messenger RNA (mRNA)  Transfer RNA (tRNA)  Ribosomal RNA (rRNA) Uracil

10. DNA  RNA  Protein DNARNAProtein Transcription Translation Central Dogma of Molecular Biology

11.  RNA is Produced by copying one of the two strands of a DNA molecule in the 5’ to 3’ direction in a process called DNA Transcription  In DNA Transcription…  RNA molecules synthesized by RNA polymerase enzyme  RNA polymerase binds to promoter region on DNA  Promoter region contains start site  Transcription ends at termination signal site

12.  RNA splicing: introns removed to make the mRNA  Intron – the part of a gene that is NOT translated to a protein  Exon – the part of the nucleic acid that remains after introns are removed  mRNA: contains the sequence of codons that code for a protein  Alternative splicing – when the remaining exons reconnect to form different mRNAs  Also know as Post-transcriptional modification Pre mRNA  Mature mRNA

14.  Ribosomes are made of protein and rRNA (ribosomal RNA)  mRNA goes through the ribosomes  Initiation factors: proteins that catayze the start of transcription  tRNA brings the different amino acids to the ribosome complex so that the amino acids can be attached to the growing amino acid chain  When a STOP codon is encountered, the ribosome releases the mRNA and synthesis ends  An open reading frames (ORF): a contiguous sequence of DNA starting at a start codon and ending at a STOP codon

15. http://www.youtube.com/watch?v=5bLEDd-PSTQ Check out this video for a great summary of Translation…

16. Gene = A stretch of DNA containing the information necessary for coding a protein/polypeptide  Promoter region  Transcription Factor Binding Site  Translation Start Site  Exon: coding (informative) regions of the DNA  Intron: noninformative regions between exons  Untranslated region (UTR)  Codons

17. Protein - A molecule comprising a long chain of amino acids connected by peptide bonds  There are 20 standard amino acids encoded by the universal genetic code

19.  Prokaryotes: a group of organisms that lack of nucleus membrane, such as blue-green algae and common bacteria (Escherichia coli)  It has two major taxa: Archaea and Bacteria  Eukaryotes: unicellular and multicellular organisms  Ex. yeast, fruit-fly, mouse, plants, and human

20.  In eukaryotes, transcription is complex:  Many genes contain alternating exons and introns  Introns are spliced out of mRNA  mRNA then leaves the nucleus to be translated by ribosomes  Genomic DNA: entire gene including exons and introns  The same genomic DNA can produce different proteins by alternative splicing of exons  Complementary DNA (cDNA): spliced sequence containing only exons  cDNA can be manufactured by capturing mRNA and performing reverse transcription

21. Eukaryotic Gene Structure

22.  A chromosome is a long and tightly wound DNA string (visible under a microscope)  Chromosomes can be linear or circular  Prokaryotes usually have a single chromosome, often a circular DNA molecule

23.  Eukaryotic chromosome appear in pairs (diploid), each inherited from one parent  Homologous chromosomes carry the same genes  Some genes are the same in both parents  Some genes appear in different forms called alleles, e.g., human blood type has three alleles: A, B, and O  All genes are presented in all cells, but a give cell types only expressed a small portion of the genes

24.  The genome is formed by one or more chromosomes  A genome is the entire set of all DNA contained in a cell  A human genome has 46 chromosomes  The total length of a human genome is 3 billion bases

25. SpeciesComplete Draft Assembly (Almost complete) In processTotal All1003136013363699 Eukaryotes22218156396

26. Phage phiX1745,368 HIV virus9,193 SARS29,751 Haemophilus influenzae (bacteria)1,830,000 Escherichia coli K124,600,000 Saccharomyces cerevisiae (yeast)12,500,000 Drosophila melanogaster (fruit fly)180,000,000 Arabidopsis thaliana (thale cress)125,000,000 Homo sapiens (human)3,000,000,000 DNA Sequence size is measured as base pairs (bp)

31.  In a few short years, mapping a persons genome will be a routine hospital test  A Genome can reveal not only an individuals health information, but also the health information of their family  A Genome in the ‘wrong hands’ can lead to Genetic Discrimination  Genetic Discrimination can prevent people from obtaining health insurance and jobs

32.  You will be responsible for storing this highly sensitive information in a Secure, Private, and Confidential Manner  You will be implementing new storage options…most Electronic Health Records are not prepared to store a genome

33.  We will talk more in depth about  Genomic Security  Genomic Ethics  Genetic Law  Risk Perception and Health Behavior  Genomic Responsibility

34. Please email me with questions bwl6@pitt.edu