Functional analysis of human promoter polymorphisms

被引:198
作者
Hoogendoorn, B [1 ]
Coleman, SL [1 ]
Guy, CA [1 ]
Smith, K [1 ]
Bowen, T [1 ]
Buckland, PR [1 ]
O'Donovan, MC [1 ]
机构
[1] Cardiff Univ, Coll Med, Dept Psychol Med, Cardiff CF14 4XN, S Glam, Wales
关键词
D O I
10.1093/hmg/ddg246
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The potential importance of gene regulation in disease susceptibility and other inherited phenotypes has been underlined by the observation that the human genome contains fewer protein coding genes than expected. Promoter sequences are potential sources of polymorphism affecting gene expression, although to date there are no large-scale systematic studies that have determined how frequently such variants occur. We have used denaturing high performance liquid chromatography to screen the first 500 bp of the 5' flanking region of 170 opportunistically selected genes identified from the Eukaryotic Promoter Database (EPD) for common polymorphisms. Using a screening set of 16 chromosomes, sing le-nucleotide polymorphisms were found in similar to35% of genes. It was attempted to clone each of these promoters into a T-vector constructed from the reporter gene vector pGL3. The relative ability of each promoter haplotype to promote transcription of the luciferase gene was tested in each of three human cell lines (HEK293, JEG and TE671) using a co-transfected SEAP-CMV plasmid as a control. The findings suggest that around a third of promoter variants may alter gene expression to a functionally relevant extent.
引用
收藏
页码:2249 / 2254
页数:6
相关论文
共 28 条
[1]   The downstream core promoter element, DPE, is conserved from Drosophila to humans and is recognized by TAF(II)60 of Drosophila [J].
Burke, TW ;
Kadonaga, JT .
GENES & DEVELOPMENT, 1997, 11 (22) :3020-3031
[2]   Characterization of single-nucleotide polymorphisms in coding regions of human genes [J].
Cargill, M ;
Altshuler, D ;
Ireland, J ;
Sklar, P ;
Ardlie, K ;
Patil, N ;
Lane, CR ;
Lim, EP ;
Kalyanaraman, N ;
Nemesh, J ;
Ziaugra, L ;
Friedland, L ;
Rolfe, A ;
Warrington, J ;
Lipshutz, R ;
Daley, GQ ;
Lander, ES .
NATURE GENETICS, 1999, 22 (03) :231-238
[3]   Streamlined approach to functional analysis of promoter-region polymorphisms [J].
Coleman, SL ;
Hoogen-doorn, B ;
Guy, C ;
Smith, SK ;
O'Donovan, MC ;
Buckland, PR .
BIOTECHNIQUES, 2002, 33 (02) :412-+
[4]   RATES OF TRANSITION AND TRANSVERSION IN CODING SEQUENCES SINCE THE HUMAN-RODENT DIVERGENCE [J].
COLLINS, DW ;
JUKES, TH .
GENOMICS, 1994, 20 (03) :386-396
[5]   THE CPG DINUCLEOTIDE AND HUMAN GENETIC-DISEASE [J].
COOPER, DN ;
YOUSSOUFIAN, H .
HUMAN GENETICS, 1988, 78 (02) :151-155
[6]   Detection of regulatory variation in mouse genes [J].
Cowles, CR ;
Hirschhorn, JN ;
Altshuler, D ;
Lander, ES .
NATURE GENETICS, 2002, 32 (03) :432-437
[7]  
Jones AC, 1999, CLIN CHEM, V45, P1133
[8]   Variation is the spice of life [J].
Kruglyak, L ;
Nickerson, DA .
NATURE GENETICS, 2001, 27 (03) :234-236
[9]   Transactivation of involucrin, a marker of differentiation in keratinocytes, by lens epithelium-derived growth factor (LEDGF) [J].
Kubo, E ;
Fatma, N ;
Sharma, P ;
Shinohara, T ;
Chylack, LT ;
Akagi, Y ;
Singh, DP .
JOURNAL OF MOLECULAR BIOLOGY, 2002, 320 (05) :1053-1063
[10]   The new genomics: Global views of biology [J].
Lander, ES .
SCIENCE, 1996, 274 (5287) :536-539