Table 1.

Position-Effect Genes in Human Diseases^[Note]

Gene	Gene Function	Domains/Motifs	Disease	Distance ofFurthest Breakpointa(kb)	3′ or 5′ Side	Reference
PAX6	TF	Paired box and homeodomain	Aniridia	125	3′	Kleinjan et al. 2001
TWIST	TF	…	Saethre-Chotzen syndrome	260	3′	Cai et al. 2003
POU3F4	TF	POU homeodomain	X-linked deafness	900	5′	de Kok et al. 1996
PITX2	TF	Homeodomain	Rieger syndrome	90	5′	Trembath et al. 2004
GLI3	TF	Zinc finger	Greig cephalopolysyndactyly syndrome	10	3′	Wild et al. 1997
MAF	TF	bZIP	Cataract, ocular anterior segment dysgenesis, and coloboma	1,000	5′	Jamieson et al. 2002
FOXC1	TF	Forkhead	Glaucoma/autosomal dominant iridogoniodysgenesis	25/1,200	5′	Davies et al. 1999
FOXC2	TF	Forkhead	Lymphedema distichiasis	120	3′	Fang et al. 2000
FOXL2	TF	Forkhead	Blepharophimosis-ptosis-epicanthus inversus syndrome	170	5′	Crisponi et al. 2004
SOX9	TF	HMG box	Campomelic dysplasia	850	5′	Bagheri-Fam et al. 2001; Pop et al. 2004
SRY	TF	HMG box	Sex reversal	3	5′/3′	McElreavy et al. 1992
SIX3	TF	Homeodomain	Holoprosencephaly (HPE2)	<200	5′	Wallis et al. 1999
SHH	Signaling	…	Holoprosencephaly (HPE3)	265	5′	Roessler et al. 1997
SHH	Signaling	…	Preaxial polydactyly	1,000	5′	Lettice et al. 2003
SHFM1	TF	DLX5/DLX6?	Split-hand/split-foot malformation	∼450	5′/3′	Crackower et al. 1996
FSHD	??	…	Facioscapulohumeral dystrophy	100	3′	Gabellini et al. 2002; Jiang et al. 2003; Masny et al. 2004
HBB	Oxygen carrier	Globin	γβ-Thalassemia	50	5′	Kioussis et al. 1983
HBA	Oxygen carrier	Globin	α-Thalassemia	18	3′	Tufarelli et al. 2003
Hoxd complex	TF	Homeodomain	Mesomelic dysplasia and vertebral defects	60	3′	Spitz et al. 2002
LCT	Enzyme	Lactase	Lactase persistence	15/20	5′	Enattah et al. 2002

Note.— TF = transcription factor.

^aIn the case of 3′ breakpoints, the distance refers to the distance from the breakpoint to the 3′ end of the gene or complex.