The contribution of exon-skipping events on chromosome 22 to protein coding diversity - PubMed (original) (raw)
The contribution of exon-skipping events on chromosome 22 to protein coding diversity
W A Hide et al. Genome Res. 2001 Nov.
Abstract
Completion of the human genome sequence provides evidence for a gene count with lower bound 30,000-40,000. Significant protein complexity may derive in part from multiple transcript isoforms. Recent EST based studies have revealed that alternate transcription, including alternative splicing, polyadenylation and transcription start sites, occurs within at least 30-40% of human genes. Transcript form surveys have yet to integrate the genomic context, expression, frequency, and contribution to protein diversity of isoform variation. We determine here the degree to which protein coding diversity may be influenced by alternate expression of transcripts by exhaustive manual confirmation of genome sequence annotation, and comparison to available transcript data to accurately associate skipped exon isoforms with genomic sequence. Relative expression levels of transcripts are estimated from EST database representation. The rigorous in silico method accurately identifies exon skipping using verified genome sequence. 545 genes have been studied in this first hand-curated assessment of exon skipping on chromosome 22. Combining manual assessment with software screening of exon boundaries provides a highly accurate and internally consistent indication of skipping frequency. 57 of 62 exon skipping events occur in the protein coding regions of 52 genes. A single gene, (FBXO7) expresses an exon repetition. 59% of highly represented multi-exon genes are likely to express exon-skipped isoforms in ratios that vary from 1:1 to 1:>100. The proportion of all transcripts corresponding to multi-exon genes that exhibit an exon skip is estimated to be 5%.
Similar articles
- The role of common single-nucleotide polymorphisms on exon 9 and exon 12 skipping in nonmutated CFTR alleles.
Steiner B, Truninger K, Sanz J, Schaller A, Gallati S. Steiner B, et al. Hum Mutat. 2004 Aug;24(2):120-9. doi: 10.1002/humu.20064. Hum Mutat. 2004. PMID: 15241793 - Sequence conservation, relative isoform frequencies, and nonsense-mediated decay in evolutionarily conserved alternative splicing.
Baek D, Green P. Baek D, et al. Proc Natl Acad Sci U S A. 2005 Sep 6;102(36):12813-8. doi: 10.1073/pnas.0506139102. Epub 2005 Aug 25. Proc Natl Acad Sci U S A. 2005. PMID: 16123126 Free PMC article. - A survey of alternative transcripts of human tissue kallikrein genes.
Kurlender L, Borgono C, Michael IP, Obiezu C, Elliott MB, Yousef GM, Diamandis EP. Kurlender L, et al. Biochim Biophys Acta. 2005 May 25;1755(1):1-14. doi: 10.1016/j.bbcan.2005.02.001. Epub 2005 Mar 10. Biochim Biophys Acta. 2005. PMID: 15878240 Review. - The Protein-Coding Human Genome: Annotating High-Hanging Fruits.
Hatje K, Mühlhausen S, Simm D, Kollmar M. Hatje K, et al. Bioessays. 2019 Nov;41(11):e1900066. doi: 10.1002/bies.201900066. Epub 2019 Sep 23. Bioessays. 2019. PMID: 31544971 Review.
Cited by
- Elucidation of the Landscape of Alternatively Spliced Genes and Features in the Dorsal Striatum of Aggressive/Aggression-Deprived Mice in the Model of Chronic Social Conflicts.
Babenko V, Redina O, Smagin D, Kovalenko I, Galyamina A, Kudryavtseva N. Babenko V, et al. Genes (Basel). 2023 Feb 27;14(3):599. doi: 10.3390/genes14030599. Genes (Basel). 2023. PMID: 36980872 Free PMC article. - Event Analysis: Using Transcript Events To Improve Estimates of Abundance in RNA-seq Data.
Newman JRB, Concannon P, Tardaguila M, Conesa A, McIntyre LM. Newman JRB, et al. G3 (Bethesda). 2018 Aug 30;8(9):2923-2940. doi: 10.1534/g3.118.200373. G3 (Bethesda). 2018. PMID: 30021829 Free PMC article. - Integrated analysis of differential expression and alternative splicing of non-small cell lung cancer based on RNA sequencing.
Li Z, Zhao K, Tian H. Li Z, et al. Oncol Lett. 2017 Aug;14(2):1519-1525. doi: 10.3892/ol.2017.6300. Epub 2017 Jun 2. Oncol Lett. 2017. PMID: 28789374 Free PMC article. - Gene discovery and transcript analyses in the corn smut pathogen Ustilago maydis: expressed sequence tag and genome sequence comparison.
Ho EC, Cahill MJ, Saville BJ. Ho EC, et al. BMC Genomics. 2007 Sep 24;8:334. doi: 10.1186/1471-2164-8-334. BMC Genomics. 2007. PMID: 17892571 Free PMC article. - Comparative genomics in cyprinids: common carp ESTs help the annotation of the zebrafish genome.
Christoffels A, Bartfai R, Srinivasan H, Komen H, Orban L. Christoffels A, et al. BMC Bioinformatics. 2006 Dec 18;7 Suppl 5(Suppl 5):S2. doi: 10.1186/1471-2105-7-S5-S2. BMC Bioinformatics. 2006. PMID: 17254304 Free PMC article.
References
- Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ. Basic local alignment search tool. J Mol Biol. 1990;215:403–410. - PubMed
- Andreadis A, Gallego ME, Nadal-Ginard B. Generation of protein isoform diversity by alternative splicing: Mechanistic and biological implications. Annu Rev Cell Biol. 1987;3:207–242. - PubMed
- Brett D, Lehmann G, Hanke J, Gross S, Reich J, Bork P. EST analysis online: WWW tools for detection of SNPs and alternative splice forms. Trends Genet. 2000;16:416–418. - PubMed
- Croft L, Schandorff S, Clark F, Burrage K, Arctander P, Mattick JS. ISIS, the intron information system, reveals the high frequency of alternative splicing in the human genome. Nat Genet. 2000;24:340–341. - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Research Materials