The impact of cis-acting polymorphisms on the human phenotype

Jones, Bryony L.; Swallow, Dallas M.

doi:10.1007/s11568-011-9155-4

The HUGO Journal

Official Journal of the Human Genome Organisation

Table 1 Examples of cis-acting functional variants thought to affect human phenotypic characteristics

From: The impact of cis-acting polymorphisms on the human phenotype

Gene	Variant	Effect	Phenotype/disease risk	Methods to show function	Reference(s)
ADH1B	C>A rs1229982 in proximal promoter	Increases promoter activity 1.4 fold	Associated with alcoholism	Transfections	Pochareddy and Edenberg (2011)
DARC	T-46C	Impairs promoter activity	Resistance to malaria	Transfections	Tournamille et al. (1995)
FMO3	Promoter haplotypes (1 kb)	‘2’ 8 fold increase in activity, ‘8’ & ‘15’ loss of activity	‘8’ & ‘15’ may contribute to trimethylaminuria	Transfections	Koukouritaki et al. (2005)
IL6	Promoter haplotype variation	Altered IL6 expression	Various disease associations	Transfections	Terry et al. (2000)
IL10	Promoter haplotype variation	TA2 haplotype has higher levels of IL10 expression	High risk TA2 haplotype associated with trachoma susceptibility	AE	Natividad et al. (2008)
IL13	C-1055T	T increases IL13 expression	Association with asthma & allergy	Gel shift assay	van der Pouw Kraan et al. (1999)
LCT	Several in enhancer ~14 kb upstream within MCM6	Higher expression of lactase in adulthood	Lactase persistence into adult life	Transfections & gel shift assay	See Ingram et al. (2009a)
LTC ₄ S	A-444C	Altered expression	Linked to aspirin associated asthma & chronic hyperplastic eosinophilic sinusitis	AE	de Alarcon et al. (2006)
MUC5B	Several promoter haplotypes	Altered MUC5B expression	Underrepresentation of low expression haplotypes in patients with diffuse panbronchiolitis	AE & transfections	Kamio et al. (2005), Loh et al. (2010)
OCA2	Rs12913832 (21,152 bp upstream within HERC2)	Derived allele lowers promoter activity	Associated with blue eye colour in homozygotes	Transfections & gel shift assays	Eiberg et al. (2008)
SHH	Several mutations 1mb upstream in enhancer within LMBR1 (& in other species)	Altered TF binding	Preaxial polydactyly	Gel shift assay & transgenic assay in mice	Farooq et al. (2010), Lettice et al. (2008)
UGT1A1	(TA)n repeat in TATA box	(TA)7 (low expression)	Gilberts syndrome, adverse drug reactions	Transfections	Bosma et al. (1995)
UGT2B15	Promoter haplotypes (rs34010522 & rs35513228)	Altered expression	Possible links to oxazepam glucuronidation, breast and prostate cancer risk	Transfections	Sun et al. (2010)

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