Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Cis-Acting Regulatory Variation in the Human Genome
Tomi Pastinen and
Thomas J. Hudson*
The systematic screening of the human genome for genetic variantsthat affect gene regulation should advance our fundamental understandingof phenotypic diversity and lead to the identification of allelesthat modify disease risk. There are several challenges in localizingregulatory polymorphisms, including the wide spectrum of cis-actingregulatory mechanisms, the inconsistent effects of regulatoryvariants in different tissues, and the difficulty in isolatingthe causal variants that are in linkage disequilibrium withmany other variants. We discuss the current state of knowledgeand technologies used for mapping and characterizing geneticvariation controlling human gene expression.
McGill University and Genome Quebec Innovation Centre, 740 Drive Penfield Avenue, Montreal, Quebec H3A 1A4, Canada.
* To whom correspondence should be addressed. E-mail: tom.hudson{at}mcgill.ca
The editors suggest the following Related Resources on Science sites:
In Science Magazine
INTRODUCTION TO SPECIAL ISSUE
Barbara R. Jasny and Leslie Roberts (22 October 2004) Science306 (5696), 629.
[DOI: 10.1126/science.306.5696.629] |Summary »|PDF »
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
GATA transcription factors directly regulate the Parkinson's disease-linked gene {alpha}-synuclein.
C. R. Scherzer, J. A. Grass, Z. Liao, I. Pepivani, B. Zheng, A. C. Eklund, P. A. Ney, J. Ng, M. McGoldrick, B. Mollenhauer, et al. (2008)
PNAS
105, 10907-10912
|Abstract »|Full Text »|PDF »
Insulin-like growth factor-1 promoter polymorphisms and colorectal cancer: a functional genomics approach.
H-L Wong, W-P Koh, N M Probst-Hensch, D Van den Berg, M C Yu, and S A Ingles (2008)
Gut
57, 1090-1096
|Abstract »|Full Text »|PDF »
Genetic variation in Glp1r expression influences the rate of gastric emptying in mice.
K. G. Kumar, L. O. Byerley, J. Volaufova, D. J. Drucker, G. A. Churchill, R. Li, B. York, A. Zuberi, and B. K. S. Richards (2008)
Am J Physiol Regulatory Integrative Comp Physiol
294, R362-R371
|Abstract »|Full Text »|PDF »
Susceptibility to sequelae of human ocular chlamydial infection associated with allelic variation in IL10 cis-regulation.
A. Natividad, M. J. Holland, K. A. Rockett, J. Forton, N. Faal, H. M. Joof, D. C.W. Mabey, R. L. Bailey, and D. P. Kwiatkowski (2008)
Hum. Mol. Genet.
17, 323-329
|Abstract »|Full Text »|PDF »
HIF-1 regulates heritable variation and allele expression phenotypes of the macrophage immune response gene SLC11A1 from a Z-DNA forming microsatellite.
H. K. Bayele, C. Peyssonnaux, A. Giatromanolaki, W. W. Arrais-Silva, H. S. Mohamed, H. Collins, S. Giorgio, M. Koukourakis, R. S. Johnson, J. M. Blackwell, et al. (2007)
Blood
110, 3039-3048
|Abstract »|Full Text »|PDF »
In vitro assays fail to predict in vivo effects of regulatory polymorphisms.
Chromosome-specific and noisy IFNB1 transcription in individual virus-infected human primary dendritic cells.
J. Hu, S. C. Sealfon, F. Hayot, C. Jayaprakash, M. Kumar, A. C. Pendleton, A. Ganee, A. Fernandez-Sesma, T. M. Moran, and J. G. Wetmur (2007)
Nucleic Acids Res.
|Abstract »|Full Text »|PDF »
Conserved noncoding genomic sequences associated with a flowering-time quantitative trait locus in maize.
S. Salvi, G. Sponza, M. Morgante, D. Tomes, X. Niu, K. A. Fengler, R. Meeley, E. V. Ananiev, S. Svitashev, E. Bruggemann, et al. (2007)
PNAS
104, 11376-11381
|Abstract »|Full Text »|PDF »
Accurate quantitation of allele-specific expression patterns by analysis of DNA melting.
S. Jeong, Y. Hahn, Q. Rong, and K. Pfeifer (2007)
Genome Res.
17, 1093-1100
|Abstract »|Full Text »|PDF »
Relative Impact of Nucleotide and Copy Number Variation on Gene Expression Phenotypes.
B. E. Stranger, M. S. Forrest, M. Dunning, C. E. Ingle, C. Beazley, N. Thorne, R. Redon, C. P. Bird, A. de Grassi, C. Lee, et al. (2007)
Science
315, 848-853
|Abstract »|Full Text »|PDF »
Promoter SNPs in G1/S checkpoint regulators and their impact on the susceptibility to childhood leukemia.
J. Healy, H. Belanger, P. Beaulieu, M. Lariviere, D. Labuda, and D. Sinnett (2007)
Blood
109, 683-692
|Abstract »|Full Text »|PDF »
Localization of a long-range cis-regulatory element of IL13 by allelic transcript ratio mapping.
J. T. Forton, I. A. Udalova, S. Campino, K. A. Rockett, J. Hull, and D. P. Kwiatkowski (2007)
Genome Res.
17, 82-87
|Abstract »|Full Text »|PDF »
Maximum likelihood inference of imprinting and allele-specific expression from EST data.
C. Seoighe, V. Nembaware, and K. Scheffler (2006)
Bioinformatics
22, 3032-3039
|Abstract »|Full Text »|PDF »
DAPK1 variants are associated with Alzheimer's disease and allele-specific expression.
Y. Li, A. Grupe, C. Rowland, P. Nowotny, J. S.K. Kauwe, S. Smemo, A. Hinrichs, K. Tacey, T. A. Toombs, S. Kwok, et al. (2006)
Hum. Mol. Genet.
15, 2560-2568
|Abstract »|Full Text »|PDF »
Allelic mRNA expression of X-linked monoamine oxidase a (MAOA) in human brain: dissection of epigenetic and genetic factors.
J. K. Pinsonneault, A. C. Papp, and W. Sadee (2006)
Hum. Mol. Genet.
15, 2636-2649
|Abstract »|Full Text »|PDF »
Genome-wide screening for cis-regulatory variation using a classical diallel crossing scheme.
R. Kiekens, A. Vercauteren, B. Moerkerke, E. Goetghebeur, H. Van Den Daele, R. Sterken, M. Kuiper, F. van Eeuwijk, and M. Vuylsteke (2006)
Nucleic Acids Res.
34, 3677-3686
|Abstract »|Full Text »|PDF »
Effects of random mutations in the human immunodeficiency virus type 1 transcriptional promoter on viral fitness in different host cell environments..
T. van Opijnen, M. C. Boerlijst, and B. Berkhout (2006)
J. Virol.
80, 6678-6685
|Abstract »|Full Text »|PDF »
A regulatory SNP causes a human genetic disease by creating a new transcriptional promoter..
M. De Gobbi, V. Viprakasit, J. R. Hughes, C. Fisher, V. J. Buckle, H. Ayyub, R. J. Gibbons, D. Vernimmen, Y. Yoshinaga, P. de Jong, et al. (2006)
Science
312, 1215-1217
|Abstract »|Full Text »|PDF »
Influence of human genome polymorphism on gene expression..
Mapping cis-acting regulatory variation in recombinant congenic strains.
P. D. Lee, B. Ge, C. M. T. Greenwood, D. Sinnett, Y. Fortin, S. Brunet, A. Fortin, M. Takane, E. Skamene, T. Pastinen, et al. (2006)
Physiol Genomics
25, 294-302
|Abstract »|Full Text »|PDF »
Histone acetylation dependent allelic expression imbalance of BAPX1 in patients with the oculo-auriculo-vertebral spectrum.
S. Fischer, H.-J. Ludecke, D. Wieczorek, S. Bohringer, G. Gillessen-Kaesbach, and B. Horsthemke (2006)
Hum. Mol. Genet.
15, 581-587
|Abstract »|Full Text »|PDF »
Evaluation of the RET regulatory landscape reveals the biological relevance of a HSCR-implicated enhancer.
E. A. Grice, E. S. Rochelle, E. D. Green, A. Chakravarti, and A. S. McCallion (2005)
Hum. Mol. Genet.
14, 3837-3845
|Abstract »|Full Text »|PDF »
Mapping common regulatory variants to human haplotypes.
T. Pastinen, B. Ge, S. Gurd, T. Gaudin, C. Dore, M. Lemire, P. Lepage, E. Harmsen, and T. J. Hudson (2005)
Hum. Mol. Genet.
14, 3963-3971
|Abstract »|Full Text »|PDF »
Compensatory cis-trans Evolution and the Dysregulation of Gene Expression in Interspecific Hybrids of Drosophila.
C. R. Landry, P. J. Wittkopp, C. H. Taubes, J. M. Ranz, A. G. Clark, and D. L. Hartl (2005)
Genetics
171, 1813-1822
|Abstract »|Full Text »|PDF »
Survey of allelic expression using EST mining.
B. Ge, S. Gurd, T. Gaudin, C. Dore, P. Lepage, E. Harmsen, T. J. Hudson, and T. Pastinen (2005)
Genome Res.
15, 1584-1591
|Abstract »|Full Text »|PDF »
Functional promoter SNPs in cell cycle checkpoint genes.
H. Belanger, P. Beaulieu, C. Moreau, D. Labuda, T. J. Hudson, and D. Sinnett (2005)
Hum. Mol. Genet.
14, 2641-2648
|Abstract »|Full Text »|PDF »
Discovery of Novel Flavin-Containing Monooxygenase 3 (FMO3) Single Nucleotide Polymorphisms and Functional Analysis of Upstream Haplotype Variants.
S. B. Koukouritaki, M. T. Poch, E. T. Cabacungan, D. G. McCarver, and R. N. Hines (2005)
Mol. Pharmacol.
68, 383-392
|Abstract »|Full Text »|PDF »
