Developmental functional genomics and the neurospora genome
Download
1 / 23

Developmental functional genomics and the Neurospora genome - PowerPoint PPT Presentation


  • 317 Views
  • Updated On :

Developmental functional genomics and the Neurospora genome. Outline methods to gind genome-wide maps of develomental processes. What to do after the genome is done? What data do you need? What models do you need to be able to build?. First.

Related searches for Developmental functional genomics and the Neurospora genome

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

PowerPoint Slideshow about 'Developmental functional genomics and the Neurospora genome' - PamelaLan


An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript

Outline methods to gind genome wide maps of develomental processes l.jpg
Outline methods to gind genome-wide maps of develomental processes

  • What to do after the genome is done?

  • What data do you need?

  • What models do you need to be able to build?


First l.jpg
First processes

  • Describe the developing system in terms of gene expression

    • Can be used to assign genes to functional groups

    • Set baselines for perturbation experiments

    • Example: insect metamorphosis – an integrated set of developmental processes controlled by a transcriptional hierarchy that coordinates the action of hundreds of genes


Slide4 l.jpg

Genomics of insect metamorphosis processes

  • Microarray analysis revealed that 13% of assayed transcripts displayed significant changes in the first 30 hours of metamorphosis.

  • They found coordinate changes in groups of genes that provided insight into the dynamics of the process

    • Ecdysone levels up – glycolysis down

    • Metamorphosis onset- muscle-related transcripts are down


Drosophia development l.jpg
Drosophia development processes

  • Comparison of expression patterns showed that embryogenesis and metamorphosis were more similar than other growth stages (insight into how complex organisms develop).

    • It may be easier to study one phase than the other – so here is the logic for doing it.

    • It may be possible to differentiate the effects of the same genes on the two processes

  • 40% of genes differed between sexes and most of this was in the germline


Drosophila l.jpg
Drosophila processes

  • It was possible to pull out tissue-specific developmental programs

    • Could verify this with mutants (critical for first model systems)


C elegans l.jpg
C. elegans processes

  • Time course from early embryogenesis to adulthood

    • Do they know what effect growth medium has?

  • 22% of the transcripts showed significant change over this time course

  • Less evolutionarily conserved genes tend to be expressed later in life than highly conserved genes.


Differences in experiments l.jpg
Differences in experiments/ processes

  • 6 or 8 timepoints were used for C. elegans, whereas 80 were used for Drosophila

  • Suggest that these developmental studies are not necessary for other organisms in which tissues can be easily dissected. What do you think?


Examination of germline specific transcripts in c elegans l.jpg
Examination of germline-specific transcripts in C. elegans processes

  • Used germline mutant + wild type to identify these

  • 1416 (12%) were germline enriched

    • 258 oocyte enriched

    • 650 sperm enriched

    • 508 germline enriched

  • Identities indicate that posttranslational mechanisms play an important part in sperm

    • Kinses, phosphatases

  • Is this enough information for you? What would you do next? What questions would you ask?


Surprises in the c elegans story l.jpg
Surprises in the C. elegans story? processes

  • Germiline-specific genes were not on the X chromosome

  • There is no doubt more information in these datasets that will be mined in the future – if you know about them.


Is it possible to study behavior at this level l.jpg
Is it possible to study behavior at this level? processes

  • Some Drosophila behaviors are under circadian control

    • Found 134 transcripts that are cyclic

    • 25% have no known function

  • Geotaxis (moving with or against gravity, polygenic trait

    • Found several hundred differentially expressed genes

    • Found three genes that when mutated resulted in geotaxis defects


Genomics in model systems to study human disease l.jpg
Genomics in model systems to study human disease processes

  • Leptin knockout mice vs wild type

    • Found 2000 detectably expressed genes and 450 were significantly different in mutant obese mice and wild type.

    • Added leptin back to ob mice to distinguish specific effects of leptin

    • Identified a transcription factor downregulated by leptin that regulates fatty-acid biosynthesis


More disease models l.jpg
More disease models processes

  • MS

  • Retinal diseases -mouse

    • Identified 396 genes, looked for rod-specific expresion. Human orthologs exist for 237. In all, 86 of the newly identified genes correspond to 37 different disease loci


Regulatory networks l.jpg
Regulatory networks processes

  • How can multiple types of information be integrated?

  • Modules – multiple, adjacent cis-regulatory elements

  • “Building the core of the regulatory circuitry by determining the relationships between cis-regulatory sequences, regulatory proteins, and gene expression seems a first step in delineating developmental networks”


Genome wide analysis of transcription factor binding site interactions l.jpg
Genome-wide analysis of transcription –factor/binding-site interactions

  • ChIP (chromatin immunoprecipitation) – identify what genes transcription factors are interacting with. (Cross-link binding proteins to DNA. Shear DNA and IP. Label and hybridize DNA to identify genes to which factors are bound.


Be careful l.jpg
Be careful interactions

  • 9 transcription factors govern the yeast cell cycle (?)

  • Look at what these bind

  • Only 213 of 800 cell cycle genes are boudn by these.


Comparative genomics l.jpg
Comparative genomics interactions

  • Can sequence important regions of closely related species to understand regulatory regions (Lander in Nature/Johnston in Science)


Future l.jpg
Future interactions

  • Localization and processing of RNA

  • Post translational modifications

  • Integration of data “data currently being generated is..systematic but also superficial.”

  • Much of the data leads to speculative discorse


Neurospora genome l.jpg
Neurospora genome interactions

  • There are many of these types of papers.

  • Sequence a genome, assemble it (this is an enormous amount of work) – then come up with the beginning of analyses that says this was worth doing.

  • 40 megabases – a little over 2X yeast.

  • 10K genes, only 25% fewer than Drosophila and almost 2X that of yeast.


Neurospora l.jpg
Neurospora - interactions

  • Intro gives the placement of this organism – why is it important?

  • >20-fold sequence coverage

  • Have 958 sequence contigs, with 97% of the sequence in the largest 44 contigs

  • 41% of the genes aren’t found in other organisms

  • Important organism for studying epigenetics



Genome papers l.jpg
Genome papers interactions

  • What is there?

    • Sequence information

    • Genes

    • Pathways

    • Potential utility of the sequence

    • Comparative analysis with other genomes

    • Some researchers continue sequence analyses others move to functional genomics


Webpages l.jpg
Webpages interactions

  • All genome projects have a webpage:

  • http://www-genome.wi.mit.edu/.

  • www.tigr.org

  • Also see webpages for this class (GOLD)


ad