An Introduction to Genomics and Personalized Health Care

Bailee LudwigQuality Management

Before we get started….

….Let’s see what you know about Genomics

DNA 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…

What exactly is DNA? 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 PyrimidinesThymine (T)Cytosine (C)

Adenine (A) pairs with Thymine (T)

Guanine (G) pairs with Cytosine (C)

Hydrogen Bonds

Sugar – Phosphate “Backbone

”

Nucleotide “Bases”

DNA SequencingA 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)

What is RNA? 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

DNA RNA Protein

DNA RNA Protein

Transcription Translation

Central Dogma of Molecular Biology

TranscriptionDNA RNA

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 enzymeRNA polymerase binds to promoter region on DNAPromoter region contains start siteTranscription ends at termination signal site

Splicing & Alternative Splicing 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

TranslationRNA - Protein

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

http://www.youtube.com/watch?v=5bLEDd-PSTQ

Check out this video for a great summary of Translation…

Genes 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

ProteinDNA RNA Protein 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

Cell TypesProkaryotes: 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 organismsEx. yeast, fruit-fly, mouse, plants, and human

Eukaryotes 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

Eukaryotic Gene Structure

Chromosomes 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

Chromosomes (2) Eukaryotic chromosome appear in pairs (diploid),

each inherited from one parentHomologous chromosomes carry the same genesSome genes are the same in both parentsSome 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

Genomes

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

Genome Sequences

Species Complete Draft Assembly(Almost complete) In process Total

All 1003 1360 1336 3699Eukaryotes 22 218 156 396

Phage phiX174 5,368

HIV virus 9,193

SARS 29,751

Haemophilus influenzae (bacteria) 1,830,000

Escherichia coli K12 4,600,000

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

Genome Sequence SizesDNA Sequence size is measured as base pairs (bp)

The Whole Picture

Let’s summarize what we’ve covered today with a Video….

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I’m sure right now you’re thinking…

This review of Bio 1 has been wonderful, but how

does it apply to HIM??

Did you know..? In a few short years, mapping a persons

genome will be a routine hospital testA 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

As HIM Professionals…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

Next Lecture…We will talk more in depth about

Genomic SecurityGenomic EthicsGenetic LawRisk Perception and Health BehaviorGenomic Responsibility

Thank-you!Please email me with

questionsbwl6@pitt.edu