Summary
The HLA data from nine published studies on Type 1 (insulin-dependent) diabetes were examined to see whether a three-allele model for the inheritance of Type 1 diabetes at the HLA-associated locus could be rejected. None of the data rejected the three-allele model. The data were also examined to see whether they would reject a recessive model. Out of the nine data sets, five rejected a recessive and four did not. The p value for all studies together rejected a recessive. Two of the data sets allowed us to test the hypothesis that multiplex and simplex families would exhibit different modes of inheritance. Multiplex data from both data sets rejected recessive inheritance while the multiplex data from only one data set also rejected three-allele inheritance. The results of assuming a recessive model and analyzing the data from simplex families led to different results from the two data sets. In addition, data from a non-European population were examined and found to reject both recessive and three-allele inheritance for Type 1 diabetes at the HLA-associated locus.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Hodge SE, Rotter JI, Lange KL (1980) A three-allele model for heterogeneity in juvenile-onset insulin-dependent diabetes. Ann Hum Genet 43: 399–412
Greenberg DA, Anderson E (1983) The search for heterogeneity in insulin dependent diabetes mellitus: evidence for familial and non-familial forms. Am J Med Genet 14: 487–499
Risch N (1983) A general model for disease-marker association, Ann Hum Genet 47: 245–252
Barbosa J, Bach FH, Rich SS (1982) Genetic heterogeneity of diabetes and HLA. Clin Genet 21: 25–32
Greenberg DA, Hodge SE, Rotter JI (1982) Evidence for recessive and against dominant inheritance at the HLA “linked” locus in coeliac disease. Am J Hum Genet 34: 263–277
Thomson G (1983) Investigation of the mode of inheritance of the HLA associated diseases by the method of antigen genotype frequencies among diseased individuals. Tissue Antigens 21: 81–104
de Jongh BM, Bruining GJ, Schreuder GMTh, Schuurman RKB, Radder JK, van Loghem E, Kahn PM, Hauptmann G, van Rood JJ (1984) HLA ands GM in insulin dependent diabetes in the Netherlands: report on a combined multiplex and family population study, Hum Immunol 10: 5–21
Anderson CE, Hodge SE, Rubin R, Rotter JI, Terasaki PI, Irvine WJ, Rimoin DL (1983) A search for heterogeneity in insulin dependent diabetes mellitus: HLA and autoimmune studies in simplex, multiplex and multigenerational families, Metabolism 32: 471–477
Hodge SE, Anderson CE, Neiswanger K, Rubin R, Sparkes RS, Sparkes MC, Crist M, Spence MA, Terasaki PI, Rimoin DL, Rotter JI (1983) Association studies between Type 1 (insulin-dependent) diabetes and 27 genetic markers: lack of association between Type 1 diabetes and Kidd blood group. Diabetologia 25: 343–347
Brautbar C, Karp M, Amar A, Cohen I, Cohen O, Sharon R, Topper E, Levene C, Cohen T (1981) Genetics of insulin dependent diabetes mellitus in Israel: population and family study. Hum Immunol 3: 1–12
Christy M, Green A, Christau B, Kormann H, Nerup J, Platz P, Thomson M, Ryder LP, Svejgaard A (1979) Studies of the HLA System and insulin dependent diabetes mellitus. Diabetes Care 2: 209–214
Risch N (1984) Segregation analysis incorporating linkage markers. I. Single-locus models with an application to Type 1 diabetes, Am J Hum Genet 36: 363–386
Falk CT (1984) A two-susceptibility-allele model for genetic disease and associated marker loci: differences and similarities to a one-s-allele model. Ann Hum Genet 48: 87–95
Payami H, Thomson G, Louis EJ (1984) The affected sibling method. III. Selection and recombination, Am J Hum Genet 36: 352–362
Farid NR, Sampson L, Noel P, Barnard JM, Davis AJ, Hillman DA (1979) HLA-D-related (DRw) antigens in juvenile diabetes mellitus. Diabetes 28: 552–557
Ginsberg-Fellner F, Dobersen MJ, Witt ME, Rayfield EJ, Rubenstein P, Notkins AL (1982) HLA antigens, cytoplasmic islet cell antibodies, and carbohydrate tolerance in families of children with insulin dependent diabetes mellitus, Diabetes, 31: 292–298
Suciu-Foca N, Rubenstein P, Nicholson J, Susinno E, Weiner J, Godfrey M, Hardy M, Rayfield E, Reemtsma K (1979) Juvenile diabetes mellitus and the HLA system. Transplant Proc xi: 1309–1313
Wolf E, Spencer KM, Cudworth AG (1983) The genetic susceptibility to Type 1 (insulin-dependent) diabetes: analysis of the HLA-DR association. Diabetologia, 24: 224–230
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Greenberg, D.A. Will a three-allele model of inheritance explain the HLA data for Type 1 (insulin-dependent) diabetes?. Diabetologia 28, 122–127 (1985). https://doi.org/10.1007/BF00273857
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00273857