Genomics
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Genomics. What can DNA tell you?. Tools for handling and analyzing DNA. Restriction endonucleases PCR Separation technologies Hybridization RFLP analysis Very useful for analyzing specific regions of DNA Technologies developed during 1970s and 1980s. Genomics: the bigger picture.

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Genomics

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Genomics

Genomics

What can DNA tell you?


Tools for handling and analyzing dna

Tools for handling and analyzing DNA

  • Restriction endonucleases

  • PCR

  • Separation technologies

  • Hybridization

  • RFLP analysis

  • Very useful for analyzing specific regions of DNA

  • Technologies developed during 1970s and 1980s


Genomics the bigger picture

Genomics: the bigger picture

  • 1990s-present

  • Complete genomic sequences are available

    • Evolutionary biology: relatedness among species

      • Ancient and modern DNA

      • Relatedness of primates

    • Comparing different members of the same species

      • Why are Great Danes and Chihuahuas so different?

    • Epidemiology: where did that flu strain come from?


How to you compare genomes

How to you compare genomes?

  • The whole sequence? What are you looking for?

  • Techniques

    • PCR

      • Microsatellite sequences: STRs, VNTRs (lots of polymorphisms)

      • Advantages: you don’t need a phenotype

      • You don’t even need to know anything about the genes!

      • Used in DNA fingerprinting (forensics, paternity)


Jargon alert

Jargon alert!

  • SNPs (single nucleotide polymorphisms)

    • Used for “finer” analysis of alleles (you don’t always see changes in restriction sites)

  • Markers

    • Early 1970s: restriction enzyme analysis

    • 1975: Southern hybridization

    • Late 1970s: DNA sequencing

    • 1980: Hypervariable locus


Genomics

Alec Jeffreys

First “minisatellite” DNA

identified.

“Father of DNA fingerprinting”

See story on p. 312 of textbook


What is a polymorphic repeat locus

What is a polymorphic repeat locus?

  • The first discovered (1989): CACACA…n

  • Number of CA repeats can vary

  • CA repeats may be located at more than one site in genome

  • Different people have different arrangements

  • Use PCR to find them and compare patterns


Genomics

DNA fingerprint

Blood stain compared

to seven different people

Which one matches?


Genomics

In situ hybridization

You can find the location

of sequences on

chromosomes this way


Genomics

How can you apply genome comparison?

Conservation biology


Genomics

Evolutionary biology

Organisms that look

alike may not necessarily

be alike


Genomics

Epidemiology: where did a disease-causing organism come from?


How do genomes change

How do genomes change?

  • Short term

    • Recombination

    • Independent assortment

  • Long term

    • Mutations- point, duplications, insertions, deletions, translocations

      • Natural selection

      • Neutral mutations


Comparing genomes

Comparing genomes

  • Cytogenetics- what do the chromosomes look like?

    • Karyotype

    • Look at the whole chromosome

  • chromosome exercise

  • Hybridization

    • Look at specific regions of the chromosome


The human genome project

The Human Genome Project

  • Federally funded, 1990: DOE and NIH

  • Initial goals: develop maps of the human genome; complete the human genome sequence by 2005

  • Whose human genome is it?

  • Requirements:

    • Build computers to manage the data

    • Develop new sequencing techniques


Genomics

Model organisms


Genomics

Chromosomal- which band

Linkage- which genes are inherited together

Physical- where exactly are the genes located


Is that all there is

Is that all there is?

  • Functional genomics

    • Where are the genes; what do they do; how are they regulated; what happens when they don’t work

  • Proteomics

    • What do the proteins look like

    • How do they work

    • How do they interact with other proteins

    • (You can’t study one gene at a time!)


Personal genomics

Personal genomics

  • So you want your own genetic map

  • How much does it cost?

  • What will you do with the information?

  • What is the benefit?

  • Example: Pharmacogenomics (not all drugs work for everyone)


Some categories of genes based on current knowledge

Some categories of genes (based on current knowledge)

  • Where you can take action:

    • BRCA1 and BRCA 2 (breast and ovarian cancer)

    • FBN1 (Marfan syndrome)

  • Do you really want to know?

    • apoE (Alzheimer’s disease)

    • PRNP (prion disease)

  • Is this helpful to the subject?

    • F5 (Factor V Leiden)

    • FMR1 (fragile-X syndrome)

    • My Genome, Myself (2009)


Genealogy and gene mapping

Genealogy and Gene mapping

  • Ancestry.com

  • Will analyze your DNA (for a small fee) and compare it to other samples in the database

  • 700,000 genetic markers per customer!

  • Other companies:

    • 23andMe (150,000 subscribers)

    • Family Tree DNA (600,000 subscribers)

    • All you need is saliva (and a small fee)


Summary

Summary

  • The last 40 years has seen a revolution in DNA technology

  • Not all inherited DNA information is contained in genes

  • Genomic information is becoming more widely available

  • When and how to use it is a subject for debate and discussion


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