Type 1 (insulin-dependent) diabetes and a highly variable locus close to the insulin gene on chromosome 11.
A polymorphic DNA sequence in the 5'-flanking region of the human insulin gene was studied in relation to Type 1 (insulin-dependent) diabetes. In 141 Caucasoid subjects analysed by Southern blot hybridisation techniques, two major DNA insertions were observed: a Class 1 allele or a Class 3 allele. The Class 2 allele was not observed in this group of subjects. Genotype frequencies in a control population (n = 88) were: homozygous 1/1, 42%; heterozygous 1/3, 50%; and homozygous 3/3, 8%. Corresponding genotype frequencies in 53 Type 1 diabetic patients were 79%, 21% and 0%, respectively (p less than 0.0005 from chi 2 test). This confirms prevalence data reported by Bell et al. [16]. There appeared to be no coinheritance with HLA-DR3/DR4 related antigens, nor with autoimmune features. Analysis of 17 Type 1 diabetic pedigrees including 34 diabetic and 69 non-diabetic subjects did not demonstrate genetic linkage of these DNA inserts with diabetes, using an autosomal recessive, single locus model of inheritance.
Hitman
G A
GA
Tarn
A C
AC
Winter
R M
RM
Drummond
V
V
Williams
L G
LG
Jowett
N I
NI
Bottazzo
G F
GF
Galton
D J
DJ
D000483:Alleles; D002906:Chromosomes, Human, 6-12 and X; D004251:DNA Transposable Elements; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D005838:Genotype; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D006801:Humans; D007328:Insulin / Q000235:genetics*; D008297:Male; D010375:Pedigree
D004251:DNA Transposable Elements; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; D007328:Insulin