Repro Exam 2: Evans Bioinformatics

Front 1

What is a genome?

Back 1

A specific sequence of genes
the reference sequence
a consequence of a genes

Front 2

how many genomes are in you?

Back 2

in each individual cell has a genome
but each cell's are identical

not identical in gametes and mutations

Front 3

What is an example of a living cell with mutations?

Back 3

cancer

Front 4

What is also different from all genomes in the body?

Back 4

mitochrondrial genomes

also microbiome - most of cells are bacteria

Front 5

objectives for today

Back 5

1. Define genomics, personalized medicine and molecular diagnostics

2. Discuss the potential impact of personalized medicine and molecular diagnostics on care delivery

3. Discuss how the rapid technological advances in the field of genomics are changing our understanding of disease and diagnosis

Front 6

What do molecular diagnostics look at?

Back 6

Nucleic acid molecules
clinical relevance of genomics
translation from bench to bedside as
"molecular diagnostics"

Front 7

What is personal medicine?

Back 7

Tailoring care to a patients’ individual variability with high (molecular) specificity

Front 8

What is Looking at disease at a molecular and genetic level

RNA and DNA - nucleic acid analytes?

Back 8

Molecular Diagnostics (MDx)

Front 9

What does a genotype look at for molecular diagnostics?

Back 9

How the tissue will behave

Front 10

What does gene expression look at in molecular diagnostics?

Back 10

how is it behaving right now

Front 11

What does the genotype in molecular Diagnostics look at?

(what cells)

Back 11

Germ line cells*****EXAM

Front 12

If you look at predisposition of nucleic acid analytes what are you looking at?

Back 12

Germline DNA

Front 13

If you are looking at "differential gene expression"
tests involving nucleic acid analytes what
are you looking at?

Back 13

RNA
protein expression - profile seen in nl and non-nl tissue

Front 14

What are some different techniques that can
be used to look at Molecular Diagnostics?

Back 14

Reverse transcriptase polymerase chain reaction (RT-PCR)
Fluorescence In-Situ Hybridization (FISH)
Microarrays
Whole-genome resequencing (starting to catch on)

Front 15

What are clinical applications of molecular Diagnostics

Back 15

Predisposition – mendelian disorder, specific mutations inherited from ancestros

Screening / Detection

Diagnosis

Prognosis / Treatment Planning
Monitoring

Pharmacogenomics – means drugs prescribed based on a person’s genes how effective are drugs? Some respond better then others

Front 16

Let's look at some molecular diagnostic examples

Back 16

woo get super pumped
lol

Front 17

What is the Herceptin HER2+ test?

Back 17

First drug with genomic labeling
molecular test required

Guides Treatment

Front 18

What does the Myriad BRCA screen?

Back 18

looks at risk / predisposition

Myriad looks at germline DNA, HER2+, Pathwork, and Exact – look at somatic mutations

Front 19

What does CUP test examine?

Back 19

Diagnoses metastatic disease
only heavy duty molecular diagnostic approved by the FDA so far
can tell where primary cancer started

Front 20

What is exact sciences colon cancer screen?

Back 20

Less invasive/scary than colonscopy - home-based stool sample collection
Tests for genetic abnormalities in cells shed from colon lining
Scheduled for FDA consideration in 2012

Front 21

How are cells genetic state machines?

Back 21

Rather than observing proxies (proteins, gross phenotype), we can observe genes directly

Most look at proxies today

We can probe gene structure and expression for reliable disease markers

Front 22

Is my cancer the same as your cancer?

Back 22

probably NOT

…even if they look the same under a microscope

MDx lets us more finely categorize disease and target therapies – no more “one drug fits all”

Get to the right treatment faster (reduce trial and error)

Front 23

What is next generation sequencing?

Back 23

Moore's law: computing power doubles about every 2 years (at the same price point)

breakpoint toward the end of 07 – the advent of so called “next generation” or “next-gen” sequencing technologies – basically, faster, cheaper, smaller machines using ingenious new techniques

Front 24

What will be the impact on my practice?

Back 24

More powerful and accurate diagnostics, more targeted therapies available

Front 25

What is the only FDA celared test?

Back 25

Currently, only Pathwork CUP test has cleared FDA – but many more are in the pipeline, and advanced sequencing will accelerate this

Front 26

What will pts want to know?

Back 26

1. more pts coming to you with their genetic info

2. A delunge of new tests and therapies is coming

3. Therapies, FDA will lag behind data generation

Front 27

What are orphan and ultra orphan drugs?

Back 27

‘orphan’ and even ‘ultra-orphan’ drugs are on the rise – high price, few patients

directed toward specific tx for a low number of people

Challenge – personalized medicine will
deluge us with “orphan” therapies, as common disorders fragment into rare subtypes

Front 28

What challenge remains in missing heritability?

Back 28

Predisposition testing still weak, for the most part
Next-gen sequencing will likely improve this (more rare variants, epigenetic info, etc.)

Front 29

Summary

What is on the EXAM*****

Back 29

Genomics, molecular diagnostics and bioinformatics are going to revolutionize, and personalize, the practice of medicine

The field is evolving at a very fast pace, and it’s becoming cheaper, faster and easier to generate personal genomic data

Significant challenges remain, both in terms of our understanding of these data, and in our ability to handle it in ever-increasing volumes – but there is formidable momentum behind the field (we’ll get there)