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Table 1
Summary of allelic heterogeneity in support of the common disease/common variant or multiallele/multilocus hypotheses
Disease type	Locus	Allele	Trait	Frequency	Effect	Comments

(a) Common disease/common variant hypothesis
Cardiovascular	APOE	*E4	Alzheimer	0.10-0.15	Early onset	Allele present in primates and all world
			disease	(Caucasian)		populations; possible interaction with
						dietary fats; may account for 20% of
						Alzheimer disease
			Age-related	0.10-0.15	Decreased risk	Well-established protective effect on
			macular			age-related macular degeneration
			degeneration
			Cardiovascular	0.10-0.15	Increased risk	Accounts for 10-16% of plasma
			disease			cholesterol variance (western
						populations); increases risk of
						cardiovascular disease (odds ratio
						approximately 1.5)
	F5	R506Q	Venous	0.02-0.08	Increased risk	Carriers have around 10% lifetime risk
			thrombosis			for significant venous thrombosis
Metabolic/	PPARG	P12A	Type 2 diabetes	0.85	Increased risk	Relative risk 1.25
nutritional			mellitus	(Caucasian)
	CAPN10	Haplotypes	Type 2 diabetes	0.03-0.29 (low	Increased risk in	Complex risk haplotypes that may
		112 and 121	mellitus	to high risk	121/112 haplotype	include several SNPs, including
				populations)	heterozygotes	CAPN10-g.4852G/A (UCSNP-43)
	HFE	C282Y	Haemochromatosis	0.05	Around 40% risk	High frequency in Caucasians, low in
				(Caucasian)	for homozygotes	Asiatics (suggesting admixture), so it may
						be a recent mutation (less than 50,000
						years ago)
Cancer	ELAC2	S217L	Prostate cancer	0.30 and 0.04	Increased risk	Odds ratio 2.4-3.1
		and A541T		(Caucasian)
	BRCA2	N372H	Breast cancer	0.22-0.29	Increased risk	Relative risk = 1.31 for HH compared to
				(Caucasian)		NN genotypes
Infectious/	MHC class I	HLA-B*2702,	Ankylosing	0.09	Increased risk	Odds ratio approximately 170, mechanism
inflammatory		04, 05	spondylitis	(Caucasian)		unclear; also associated with reactive
						arthritis and uveitis; about 2% of B27-
						positive carriers develop ankylosing
						spondylitis
	MHC class II	DQB1*0302-	Type 1 diabetes	0.05	Increased risk	Around 10% of heterozygotes for these
		DRB1*0401/	mellitus	(European)		high risk haplotypes develop type 1
		DQB1*0201-				diabetes mellitus; relative risk
						approximately 20
		DRB1*03
	IL12B	3' UTR	Type 1 diabetes	0.79	Increased risk	Interaction with HLA; increased
		allele 1	mellitus	(Caucasian)		expression of IL12B in vitro

	G6PD	A^-	G6PD deficiency	Approximately	Decreased risk of	High allele frequency proposed to be
		(V68M/N126D)		0.20 (West	severe malaria	due to balancing selection
				African)
	HBB	HbC (E6K)	Anaemia	0.09 (West	Decreased risk of	High allele frequency proposed to be
			(homozygotes)	African)	severe malaria	due to balancing selection
	CCR5	Δ32-CCR5	HIV-1	0.09	Decreased HIV-1	Recent origin - estimated approximately
			transmission	(Caucasian)	transmission	700 years ago [13]
Developmental	PDGFRA	Promoter	Neural tube	0.23	Increased risk for	At least six polymorphic sites within
		H1/H2α	defect	(Caucasian)	sporadic neural	each haplotype
		haplotypes			tube defect
(b) Multilocus/multiallele hypothesis
Cardiovascular	LDLR	> 735 alleles	Coronary artery	All rare, except in	Increased risk of
			disease	isolate or founder	coronary artery
				populations	disease
	APOB	> 24 alleles	Coronary artery	R3500Q 0.002,	Increased risk of	Single common R3500Q allele
			disease	remainder rare	coronary artery
					disease
Cancer	BRCA1	> 483 alleles	Familial breast-	All rare, except in	Increased risk
			ovarian cancer	isolate or founder
				populations
	BRCA2	> 404 alleles	Familial breast	All rare, except in	Increased risk	Common N372H allele (frequency
			cancer	isolate or founder		approximately 0.25) with relative
				populations		risk 1.31
	MLH1	> 143 alleles	Hereditary non-	All rare	Increased risk
			polyposis colorectal
			cancer (HNPCC)
	MSH2	> 108 alleles	Hereditary non-	All rare	Increased risk
			polyposis colorectal
			cancer (HNPCC)
	P53	> 144 alleles	Multiple cancers	All rare	Increased risk
Neurosensory	ABCA4	> 350 alleles	Stargardt disease,	Most rare, G863A	Increased risk
			retinitis pigmentosa	allele approximately
				0.014 (Europeans)
	RHO	> 88 alleles	Retinitis pigmentosa,	All rare	Increased risk
			congenital stationary
			night blindness
	GJB2	> 45 alleles	Non-syndromic	Most rare, 30delG	Increased risk	30delG absent from non-European
			deafness	allele around 0.015		populations
				(Europeans)
Metabolic/	CFTR	> 963 alleles	Cystic fibrosis	Most rare,
nutritional					ΔF508 accounts for	Increased risk ΔF508 allele recent
					approximately 70%	-estimated to have arisen 3,000
					of cystic fibrosis	years ago [14]
					alleles in Caucasians

Data are from the Online Mendelian inheritance in Man database [30].
Wright and Hastie Genome Biology 2001 2:comment2007.1 doi:10.1186/gb-2001-2-8-comment2007

Table 1