Targeted discovery of novel human exons by comparative genomics

@article{citeulike:1939393, abstract = {A complete and accurate set of human protein-coding gene annotations is perhaps the single most important resource for genomic research after the human-genome sequence itself, yet the major gene catalogs remain incomplete and imperfect. Here we describe a genome-wide effort, carried out as part of the Mammalian Gene Collection (MGC) project, to identify human genes not yet in the gene catalogs. Our approach was to produce gene predictions by algorithms that rely on comparative sequence data but do not require direct cDNA evidence, then to test predicted novel genes by RTPCR. We have identified 734 novel gene fragments (NGFs) containing 2188 exons with, at most, weak prior cDNA support. These NGFs correspond to an estimated 563 distinct genes, of which >160 are completely absent from the major gene catalogs, while hundreds of others represent significant extensions of known genes. The NGFs appear to be predominantly protein-coding genes rather than noncoding RNAs, unlike novel transcribed sequences identified by technologies such as tiling arrays and CAGE. They tend to be expressed at low levels and in a tissue-specific manner, and they are enriched for roles in motor activity, cell adhesion, connective tissue, and central nervous system development. Our results demonstrate that many important genes and gene fragments have been missed by traditional approaches to gene discovery but can be identified by their evolutionary signatures using comparative sequence data. However, they suggest that hundredsnot thousandsof protein-coding genes are completely missing from the current gene catalogs. 10.1101/gr.7128207}, author = {Siepel, Adam and Diekhans, Mark and Brejova, Brona and Langton, Laura and Stevens, Michael and Comstock, Charles L. and Davis, Colleen and Ewing, Brent and Oommen, Shelly and Lau, Christopher and Yu, Hung-Chun and Li, Jianfeng and Roe, Bruce A. and Green, Phil and Gerhard, Daniela S. and Temple, Gary and Haussler, David and Brent, Michael R. }, citeulike-article-id = {1939393}, doi = {10.1101/gr.7128207}, journal = {Genome Res.}, keywords = {recent\_genefinding}, month = {November}, pages = {gr.7128207+}, posted-at = {2008-02-25 21:19:22}, priority = {2}, title = {Targeted discovery of novel human exons by comparative genomics}, url = {http://dx.doi.org/10.1101/gr.7128207}, year = {2007} }

TY - JOUR ID - citeulike:1939393 L3 - citeulike-article-id:1939393 TI - Targeted discovery of novel human exons by comparative genomics JF - Genome Res. SP - gr.7128207 N2 - A complete and accurate set of human protein-coding gene annotations is perhaps the single most important resource for genomic research after the human-genome sequence itself, yet the major gene catalogs remain incomplete and imperfect. Here we describe a genome-wide effort, carried out as part of the Mammalian Gene Collection (MGC) project, to identify human genes not yet in the gene catalogs. Our approach was to produce gene predictions by algorithms that rely on comparative sequence data but do not require direct cDNA evidence, then to test predicted novel genes by RTPCR. We have identified 734 novel gene fragments (NGFs) containing 2188 exons with, at most, weak prior cDNA support. These NGFs correspond to an estimated 563 distinct genes, of which >160 are completely absent from the major gene catalogs, while hundreds of others represent significant extensions of known genes. The NGFs appear to be predominantly protein-coding genes rather than noncoding RNAs, unlike novel transcribed sequences identified by technologies such as tiling arrays and CAGE. They tend to be expressed at low levels and in a tissue-specific manner, and they are enriched for roles in motor activity, cell adhesion, connective tissue, and central nervous system development. Our results demonstrate that many important genes and gene fragments have been missed by traditional approaches to gene discovery but can be identified by their evolutionary signatures using comparative sequence data. However, they suggest that hundredsnot thousandsof protein-coding genes are completely missing from the current gene catalogs. 10.1101/gr.7128207 KW - recent_genefinding AU - Siepel, Adam AU - Diekhans, Mark AU - Brejova, Brona AU - Langton, Laura AU - Stevens, Michael AU - Comstock, Charles AU - Davis, Colleen AU - Ewing, Brent AU - Oommen, Shelly AU - Lau, Christopher AU - Yu, Hung-Chun AU - Li, Jianfeng AU - Roe, Bruce AU - Green, Phil AU - Gerhard, Daniela AU - Temple, Gary AU - Haussler, David AU - Brent, Michael PY - 2007/11/07/ UR - http://dx.doi.org/10.1101/gr.7128207 ER -