Annotating regulatory DNA based on man-mouse genomic comparison

被引：22

作者：

Dieterich, C ^{[1
]}

Cusack, B ^{[1
]}

Wang, HY ^{[1
]}

Rateitschak, K ^{[1
]}

Krause, A ^{[1
]}

Vingron, M ^{[1
]}

机构：

[1] Max Planck Inst Mol Genet, D-14195 Berlin, Germany

来源：

BIOINFORMATICS | 2002年 / 18卷

关键词：

D O I：

10.1093/bioinformatics/18.suppl_2.S84

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

Non-coding DNA segments that are conserved between the human and mouse genomic sequence are good indicators of possible regulatory sequences. Here we report on a systematic approach to delineate such conserved elements from upstream regions of orthologous gene pairs from man and mouse. We focus on orthologous genes in order to maximize our chances to find functionally similar regulatory elements. The identification of conserved elements is effected using the Waterman-Eggert local suboptimal alignment algorithm. We have modified an implementation of this algorithm such that it integrates the determination of statistical significance for the local suboptimal alignments. This has the effect of outputting a dynamically determined number of suboptimal alignments that are deemed statistically significant. Comparison with experimentally determined annotation shows a striking enrichement of regulatory sites among the conserved regions. Furthermore, the conserved regions tend to cover the promotor region described in the EPD database.

引用

收藏

页码：S84 / S90

页数：7

相关论文

共 27 条

[1] Gapped BLAST and PSI-BLAST: a new generation of protein database search programs [J].

Altschul, SF ;

Madden, TL ;

Schaffer, AA ;

Zhang, JH ;

Zhang, Z ;

Miller, W ;

Lipman, DJ .

NUCLEIC ACIDS RESEARCH, 1997, 25 (17) :3389-3402

[2] WEIGHT MATRIX DESCRIPTIONS OF 4 EUKARYOTIC RNA POLYMERASE-II PROMOTER ELEMENTS DERIVED FROM 502 UNRELATED PROMOTER SEQUENCES [J].

BUCHER, P .

JOURNAL OF MOLECULAR BIOLOGY, 1990, 212 (04) :563-578

[3] Computational identification of promoters and first exons in the human genome [J].

Davuluri, RV ;

Grosse, I ;

Zhang, MQ .

NATURE GENETICS, 2001, 29 (04) :412-417

[4] The Distributed Annotation System [J].

Dowell, Robin D. ;

Jokerst, Rodney M. ;

Day, Allen ;

Eddy, Sean R. ;

Stein, Lincoln .

BMC BIOINFORMATICS, 2001, 2 (1)

[5] STRONG CONSERVATION OF NONCODING SEQUENCES DURING VERTEBRATES EVOLUTION - POTENTIAL INVOLVEMENT IN POSTTRANSCRIPTIONAL REGULATION OF GENE-EXPRESSION [J].

DURET, L ;

DORKELD, F ;

GAUTIER, C .

NUCLEIC ACIDS RESEARCH, 1993, 21 (10) :2315-2322

[6] Comparative genome analysis delimits a chromosomal domain and identifies key regulatory elements in the α globin cluster [J].

Flint, J ;

Tufarelli, C ;

Peden, J ;

Clark, K ;

Daniels, RJ ;

Haudison, R ;

Miller, W ;

Philipsen, S ;

Tan-Un, KC ;

NcMorrow, T ;

Frampton, J ;

Alter, BP ;

Frischauf, AM ;

Higgs, DR .

HUMAN MOLECULAR GENETICS, 2001, 10 (04) :371-382

[7] Analysis of vertebrate SCL loci identifies conserved enhancers [J].

Göttgens, B ;

Barton, LM ;

Gilbert, JGR ;

Bench, AJ ;

Sanchez, MJ ;

Bahn, S ;

Mistry, S ;

Grafham, D ;

McMurray, A ;

Vaudin, M ;

Amaya, E ;

Bentley, DR ;

Green, AR .

NATURE BIOTECHNOLOGY, 2000, 18 (02) :181-186

[8] Online Mendelian Inheritance in Man (OMIM), a knowledgebase of human genes and genetic disorders [J].

Hamosh, A ;

Scott, AF ;

Amberger, J ;

Bocchini, C ;

Valle, D ;

McKusick, VA .

NUCLEIC ACIDS RESEARCH, 2002, 30 (01) :52-55

[9] Conserved noncoding sequences are reliable guides to regulatory elements [J].

Hardison, RC .

TRENDS IN GENETICS, 2000, 16 (09) :369-372

[10] Databases on transcriptional regulation: TRANSFAC, TRRD and COMPEL [J].

Heinemeyer, T ;

Wingender, E ;

Reuter, I ;

Hermjakob, H ;

Kel, AE ;

Kel, OV ;

Ignatieva, EV ;

Ananko, EA ;

Podkolodnaya, OA ;

Kolpakov, FA ;

Podkolodny, NL ;

Kolchanov, NA .

NUCLEIC ACIDS RESEARCH, 1998, 26 (01) :362-367