Abstract
The two alleles of a gene can be expressed at different levels, the extreme example being imprinting, a condition in which one allele is totally suppressed. Recently, subtle differences in the expression of the two alleles have been detected in numerous human genes and in a few cases, have been associated with a genetic predisposition to disease. The underlying mechanisms are largely unexplored.
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References
Carninci P . (2009). The long and short of RNAs. Nature 457: 974â975.
Cowles CR, Hirschhorn JN, Altshuler D, Lander ES . (2002). Detection of regulatory variation in mouse genes. Nature Genet 32: 432â437.
Gimelbrant A, Hutchinson JN, Thompson BR, Chess A . (2007). Widespread monoallelic expression on human autosomes. Science 318: 1136â1140.
Göring HHH, Curran JE, Johnson MP, Dyer TD, Charlesworth K, Cole SA et al. (2007). Discovery of expression QTLs using large-skale transcriptional profiling in human lymphocytes. Nature Genet 39: 1208â1216.
Guda K, Natale L, Lutterbaugh J, Wiesner GL, Lewis S, Tanner SM et al. (2009). Infrequent detection of germline allele-specific expression of TGFBR1 in lymphoblasts and tissues of colon cancer patients. Cancer Res 69: 4959â4961.
He Y, Vogelstein B, Velculescu VE, Papadopoulos N, Kinzler KW . (2008). The antisense transcriptomes of human cells. Science 322: 1855â1857.
Houlston RS, Webb E, Broderick P, Pittman AM, Di Bernardo MC, Lubbe S et al. (2008). Meta-analysis of genome-wide association data identifies four new susceptibility loci for colorectal cancer. Nature Genet 40: 1426â1435.
Knight JC . (2004). Allele-specific gene expression uncovered. Trends Genet 20: 113â116.
Lo HS, Wang Z, Hu Y, Yang HH, Gere S, Buetow KH et al. (2003). Allelic variation in gene expression is common in the human genome. Genome Res 13: 1855â1862.
Lynch HT, Weisenburger DD, Quinn-Laquer B, Watson P, Lynch JF, Sanger WG . (2002). Hereditary chronic lymphocytic leukemia: an extended family study and literature review. Am J Med Genet 115: 113â117.
Morley M, Molony CM, Weber TM, Devlin JL, Ewens KG, Spielman RS et al. (2004). Genetic analysis of genome-wide variation in human gene expression. Nature 430: 743â747.
Raval A, Tanner S, Byrd J, Angerman E, Perko J, Chen S-S et al. (2007). Down-regulation of death associated protein kinase 1 (DAPK1) in chronic lymphocytic leukemia. Cell 129: 879â890.
Stranger BE, Nica AC, Forrest MS, Dimas A, Bird CP, Beasley C et al. (2007). Population genomics of human gene expression. Nature Genet 39: 1217â1224.
Valle L, Serena-Acedo T, Liyanarachchi S, Hampel H, Comeras I, Li Z et al. (2008). Germline allele-specific expression of TGFBR1 confers an increased risk of colorectal cancer. Science 321: 1361â1365.
Yan H . (2002a). Small changes in expression affect predisposition to tumorigenesis. Nat Genet 30: 25â26.
Yan H . (2002b). Allelic variation in human gene expression. Science 297: 143.
Zeng Q, Phukan S, Xu Y, Sadim M, Rosman DS, Pennison M et al. (2009). Tgfbr1 haploinsufficiency is a potent modifier of colorectal cancer development. Cancer Res 69: 678â686.
Acknowledgements
Work in the author's laboratory was supported by NIH grants CA67941, CA16058 and P01 124570.
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de la Chapelle, A. Genetic predisposition to human disease: allele-specific expression and low-penetrance regulatory loci. Oncogene 28, 3345â3348 (2009). https://doi.org/10.1038/onc.2009.194
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DOI: https://doi.org/10.1038/onc.2009.194