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	# general—the presence of neutral (or near neutral) biochemical elements, of lineagespecific functional elements, and of functionally conserved but non-orthologous elements		# general—the presence of neutral (or near neutral) biochemical elements, of lineagespecific functional elements, and of functionally conserved but non-orthologous elements
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	[[Category:Readings]]		[[Category:Readings]][[Category:Rajkumar]]

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Raj at 19:19, 3 January 2010

2010-01-03T19:19:36Z

New page

This paper is about visualizing and analyzing functional landscape of human genome.
<pre>
The Encyclopedia of DNA Elements (ENCODE) Project9 aims to provide a
more biologically informative representation of the human genome by using
high-throughput methods to identify and catalogue.
the functional elements encoded

30 groups involved
30MB functional seq analised as 45 regions
15MB known 14 regions;
15MB of unclassified 30 regions

</pre>
==Salient findings==
# Human genome extensively transcribed
# Many non-coding transcripts - identified (miRNA?)
# Many unrecogonized transcription start sites - identified
# Regulatory regions are symmetrically distributed around transcription start sites
# Replication timing is correlated with chromatin structure(?!)
# 5% of the functional seq is always with the evolutionary constraits (under negative selection)
# 95% of the functional elements are evolutionarily unconstrained, potentially acting like a '''warehouse''' for natural selection
# Functional elements show great sequence variation among them
==Transcription==
GENCODE: Integrated annotations of both manual review and experimental testing procedures of cDNA and proteins

# Presence of large number of unannotated transcription elements
## validated by RT-PCR (40%)
## RACE extension of Tx.fragments to GENCODE annotated genes is usually 50-200kb
# presence of pseudo genes
# presence of non protein coding RNA
# Primery transcripts
## Coverage of all 3 technologies (ENCODE, RACE and PET Tags) across encode region shows maximum coverage compared to individual technology.
# Regulation of transcripts
## used various methods to identify the regulatory elements and made a transcription start site catalogue
## different catagories of TSS
# Replication
# Chromatin organisation
==Evolutionary constraint and population variability==

* Data
** 206MB of orthologous sequence to ENCODE from 14 mammalian species
** Sequencing by targetted and isolating strategy of individual BACs
** TBA94, MAVID95 and MLAGAN alignment
** GERP87, SCONE98 and BinCons used to identify the sequences under constraint
** Intra-specific variation is by SNP data

* constrained vs non-constrained
** examined measures of human variation (heterozygosity, derived allele-frequency spectra and indel rates) within the sequences of the experimentally identified functional elements
*** small portion of constrained seq, most of them (32%) are coding sequences and 40% of them are un -annotated sequences

* Experimentally identified functional elements and genetic variation
** within constrained seq, coding show exceesive polymorphism
** In general, non-coding seq, show excessive polymorphism

* Unexplained constrained sequences
** 40% of the ENCODE-region sequences identified as constrained are not associated with any experimental evidence of function.

* Unconstrained experimentally identified functional elements
** unexpectedly large fraction of experimentally identified functional elements show no evidence of evolutionary constraint ranging from 93% for Un.TxFrags to 12% for CDS.

==Hypothesis for presence of unconstrained func.Elements==
# Presence of miRNA: parent transcript of intronic miRNA harbours the constrained bases
# transcription of intergenic regions or specific factor binding
# general—the presence of neutral (or near neutral) biochemical elements, of lineagespecific functional elements, and of functionally conserved but non-orthologous elements
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[[Category:Readings]]

Identification and analysis of functional elements - Revision history

Raj at 08:40, 23 June 2016

Raj: 1 revision imported

Raj at 19:19, 3 January 2010