Variations on a splice theme
Systematic analysis of exon-exon junctions reveals many novel splice
variants
By Cathy Holding

Based on expressed sequence tag (EST) studies and transcriptome analysis,
alternative splicing of pre-messenger RNAs (pre-mRNAs) occurs in a temporal
and tissue-specific manner. In the December 19 Science, Jason Johnson and
colleagues at Rosetta Inpharmatics report a systematic survey method to
capture all possible splice variants that provides experimental evidence and
tissue distributions for several thousand known and novel splice isoforms.
These data demonstrate that ESTs are biased toward more highly expressed
transcripts and that they underrepresent central regions of cDNAs. This
suggests that more than 74% of human multi-exon genes are alternatively
spliced and provides possible novel therapeutic targets for diseases that
are caused by inappropriate transcript splicing events (Science,
302:2141-2144, December 19, 2003).

Johnson et al. used a set of five microarrays containing 125,000 36 bp
exon-exon junction probes from 10,000 multi-exon genes to examine 52 tissue
samples. Hybridization intensities were modeled as a function of
tissue-specific expression levels, which gave an exon-by-exon representation
of probable splice events. From these, 150 reverse transcription polymerase
chain reaction primer pairs were developed to test for the events across the
52 tissue samples, resulting in a genome-wide set of tissue-specific
alternative splice event predictions. Splicing events not represented by
ESTs were found (e.g., in the 3-hydroxy-3-methyl-glutaryl coenzyme A
reductase gene encoding the targets for the statin class of
cholesterol-lowering drugs). Of 153 transcript regions tested, 134 contained
alternative splice events not represented by mRNAs, and 92 not represented
by ESTs. Seventy three were validated by sequencing, and 53 of these were
found to be novel. In addition, using the Gene Ontology database, 31 genes
with the highest frequency of alternative splice variants were observed to
encode proteins involved in cell communication-such as receptor tyrosine
kinases-and in enzyme regulation, such as small GTPase regulation.

Read the rest at The Scientist.com
http://www.biomedcentral.com/news/20031223/01

Comment:
'Exon' is the gene rich DNA, 'Intron' is the non-coding DNA between Exon
DNA.

Posted by
Robert Karl Stonjek.
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