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Keynote: Svante Pääbo - Analyses of Pleistocene Genomes
This will probably be a very interesting talk. Just can't wait. - Tomasz Puton
Not just interesting, but most likely great. Svante is a fantastic speaker - arne
If you’re interested in human history, the genome is a great source of information. To reconstruct history, we compare sequences of people (and other species) living today. We use models of how DNA changes over time to understand the differences that exist today. This is an indirect way to study history, because we are reconstructing from the present what we think has happened in the past. - Barb Bryant
specimens are highly contaminated, .... - Venkata P. Satagopam
original work from 1984 on egyptian mummy - - Shannon McWeeney
mtDNA - advantage of many copies per cell - Mickey Kosloff
Replacement (out of africa theory) vs assimilation (i.e. geneflow from modern humans) - arne
mtDNA is extracted from a specimen from neanderthal - Venkata P. Satagopam
Started with the original neanderthal specimen - arne
The variation in human population origins before the split (as measured by mtDNA) of modern and neanderthals - arne
extract dna from skull, skip PCR and directly sequence - Mickey Kosloff
only 3.5% actually from neanderthal genome - Shannon McWeeney
Average length 50 nucleotides - arne
Vindija Cave, Croatia .... 3 bones - Venkata P. Satagopam
only about 3.5% of dna came from human - Mickey Kosloff
3 billion fragments - again most from bacteria - Shannon McWeeney
most dna is bacterial contaminants - Mickey Kosloff
avg genome cover is 1.5X - Venkata P. Satagopam
most DNA extracted is female look at Y chrom % as contaminant - Ted Laderas
Three females samples (and therefore Y chromosome contamination can be used to calculate noise). Total risk is below 1% risk of contaimination - arne
at any particular position - 1% chance contamination (broken down by source - 3 measures) - Shannon McWeeney
consistant nucleotide chemical changes at 5' and 3' ends - Mickey Kosloff
try to correct by alignments to human and chimpanzee genomes - Mickey Kosloff
Details on bioinformatics and alignment issues (led by Ed Green) can be found in Science paper - - Shannon McWeeney
55% chance of seeing a position covered by at least 1 read - Ted Laderas
Divergence to human reference genome 12% highest among human is in San 10% - arne
typical european (French) 8% divergence to human reference compared with 12% in neanderthal - Shannon McWeeney
78 amino acid substitutions ... a catalog of novel fixed features in the human genome - Venkata P. Satagopam
But this number will change - arne
novel fixed features in human genome - 78 aa substitutions (in paper) - now down to 50 - Shannon McWeeney
Three out of six proteins with 2 changes are skin expressed - arne
next focused on SNPs - Mickey Kosloff
detection of selective sweeps - look for snps in human, chimps, neanderthals - r egions where neanderthal looks all ancestral. - Shannon McWeeney
S vs cM plot - visual inspection for widest spread - Shannon McWeeney
Most extreme case in THADA, Transport and diabeted related - arne
Thada is risk allele for type 2 diabetes - implications for metabolism - Shannon McWeeney
detection of insertion in intron in Thada (not fixed in humans as initially thought in paper) - Shannon McWeeney
3-4% in europe has the neanderthal version (and are protected against Diabetes Type II) - arne
interesting follow-up research here - positive selection yet cost with risk allele - Shannon McWeeney
RUNX2: Mutations cause CCD (Cleidocranial dysplasia) - arne
annotation of others associated with autism and other diseases including CCD - Shannon McWeeney
CCD of interest due to skull morphology phenotype - Shannon McWeeney
Now comes the most surprising result. - arne
focusing on - Interbreeding with modern humans? - Venkata P. Satagopam
Work by Rasmus Nielsen - arne
Is Craig Venter a "fully modern human" ? - arne
analysis of self-identified neanderthals who write to Svante - predominantly men. - Shannon McWeeney
Comparisons to genomes of humans from different continents suggests interbreeding occured in middle east, before geographic expansion - Mickey Kosloff
:) - arne
45% men who are neandertals, 1% women are neandertals.... - Venkata P. Satagopam
future 10-20x coverage of genome - Mickey Kosloff
Future: (i) Better coverage (10-20x coverage) (ii) Functional analyses of candidate genes Exemplified by FoxP2 - arne
next topic - functional analysis of genes - foxp2 - Venkata P. Satagopam
FoxP2 is the same in human and neanderthal. - arne
hope to identify backmutations in humans -cheaper to find these people because of low cost of sequencing - Ted Laderas
easier to check phenotypes in mice - Mickey Kosloff
Human FoxP2 in mouse: The mouse can not speak ! Large scale phenotype study (323 phenotypic traits). -> More cautious in a novel area (stays close to the wall). No difference after 3 minutes. Second phenotype: Altered vocalization !!! - arne
323 phenotypic traits ... studied .. - Venkata P. Satagopam
movement more cautious in humanized mice - Venkata P. Satagopam
next one is altered vocalization - Venkata P. Satagopam
Enard et al Cell 2009 - Venkata P. Satagopam
mice with human foxp2 grew longer neurons - Mickey Kosloff
Other hominid forms........ - arne
Denisova individual 1 Myears (400 diffs in mtDNA) - arne
very good keynote - Mickey Kosloff
Keynote: Steven Brenner - Ultraconserved nonsense: gene regulation by splicing & RNA surveillance
ISMB2010 just kicked off - Venkata P. Satagopam
Prof Søren Brunak introducing Steven Brenner, ISCB overton prize winner - Venkata P. Satagopam
Brenner contributed to many fields in bioinformations, starting in structureal biology ober RNA to metagenomics. - Roland Krause
A short biography, summarizing Soren Brunaks kind introduction - Roland Krause
The morphology of steves paper: - Shannon McWeeney
Intro: The ultraconservative (as seen from Berkely) and nonsense (as found in Through the Looking Glass - Roland Krause
The jabberwocky poem does have meanings and is elegantly crafted. - Roland Krause
Generally, nonsens in biology is bad. - Roland Krause
Nonsense is generally bad, even in a codon - Venkata P. Satagopam
Truncated proteins might interfere with physiological function (dominant negative). The cell removes such transcripts through nonsense-mediated decay (NMD). - Roland Krause
Good example for NMD: Sox10 - Roland Krause
Mutations early in the gene leads to less severe phenotypes than later ones - Roland Krause
NMD is an mRNA surveillance system - Venkata P. Satagopam
NMD important to development of the immunesystem and cleans up other transcriptional errors. - Roland Krause
We do not know how NMD works outside the mammals. - Roland Krause
The mechanism involves the splicing machinery. If a stop is found wwithin 50nt upstream of the exon junction complex, it is removed.. - Roland Krause
50 nucleotide rule - translated normally or degraded by NMD - Venkata P. Satagopam
brilliant nytimes article title - surviving on low number of genes - Shannon McWeeney
splicing can introduce PTC - premature termination codon - Venkata P. Satagopam
AS as mechanism to introduce PTCs - can lead to unproductive splicing - Shannon McWeeney
these isoforms often have PTC - Venkata P. Satagopam
Humans have fewer genes but better genes, due to AS. - John Greene from fftogo
Are PTC splice forms funcitonal? - Venkata P. Satagopam
Many PTC mRNAs are noise - Venkata P. Satagopam
analgous mechanism to shrinter: - Shannon McWeeney
Humans have fewer genes but better genes, due to AS. - John Greene from fftogo
Alt splicing can yield isoforms differentially subjected to NMD - Venkata P. Satagopam
SR protein - 11 in human which are serine and arginine rich - Venkata P. Satagopam
SR proteins have premature stop codons. - Roland Krause
SR genes has mRNAs with premature termination codons - Venkata P. Satagopam
AS of PTC isoforms is mechanism for autoregulation of proteins - Ted Laderas
NMD has a large effect on isoform abundance - Venkata P. Satagopam
NMD has impact on isoform abundance - example of NMD clearing the major isoform - Shannon McWeeney
minor isoforms are only shared 25% of time - modrek and lee 2003 - Shannon McWeeney
Not just anecdotal stories, splice patterns are conserved in mouse, implying functional significance. - Roland Krause
(Unpulbished work) - Roland Krause
All the SR proteins are talking to each other - Venkata P. Satagopam
SR proteins 'compensate' for each other via coupling via AS and NMD - Ted Laderas
SR genes have ultraconversed elements .. Bejerano et al 2004 Science 304: 1321 - Venkata P. Satagopam
Most ultraconserved regions are in intergenic regions, the regions in SR within genes. - Roland Krause
question of why conserved - not protein coding, no obvious significant RNA secondary structure - Shannon McWeeney
No proteins are produced from these genes. - Roland Krause
The reason why SR sequences are highly conserved - most of the seq are not protein coding, - Venkata P. Satagopam
no repetitive elements - Venkata P. Satagopam
why conserved part 2 - no overrepresentation of binding / regulatory elements - Shannon McWeeney
No simple explanations e.g. from miRNA binding etc. - Roland Krause
no similarity elsewhere in genome except retropseudogenes - Venkata P. Satagopam
analysis on origin of unproductive splicing - Shannon McWeeney
No sequence similarity between the conserved elements. Seems to have been introduced mutliple times. - Roland Krause
mouse and human SRp55 conserved but changing - Venkata P. Satagopam
working on chordate SR proteins - Venkata P. Satagopam
here intron and exon structure is more informative - Venkata P. Satagopam
at this point - he has requested no further blogging - unpublished work - Shannon McWeeney
no blog slides may be over - Burkhard Rost
# Looks like interesting work. - Roland Krause
wonderful talk - Shannon McWeeney
Tells a (hard to blog) story about the successful treatment of collaborator with novel treatment based on genotyping. - Roland Krause
Wow - what a conclusion! Fantatic talk... - John Greene from fftogo
# Certainly great work. The talk was nice too, and he only bitched at other reseachers in person once, another step up. - Roland Krause
"Ultraconversed elements in SR genes ONLY show similarity to retropseudogenes" - what does this mean? Any takers? - Saravanamuttu Gnaneshan
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