Analysis of linkage between the major histocompatibility system and juvenile, insulin-dependent diabetes in multiplex families. Reanalysis of data.
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Linkage analysis between the major histocompatibility system (HLA) and juvenile, insulin-dependent diabetes, assuming an autosomal recessive mode and 50% penetrance was performed on 21 juvenile, insulin-dependent diabetic multiplex families (two or more diabetics per sibship) with phenotypically normal parents. The total lod score was the highest (3.98) at a recombination fraction of 13%. For a penetrance of 100%, the highest total lod score was 2.92 at a recombination fraction of 18%. These results are compatible with the existence of linkage between an autosomal recessive diabetic gene with 50% penetrance and the HLA in some of the families studied. Our ascertainment strategy would be expected to increase the likelihood of selecting for genetically homogenous diabetes and against sporadic forms of the disease. Thus, our findings may apply only to a small proportion of all cases of juvenile, insulin-dependent diabetes.
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Linkage analysis in multiplex pedigrees was largely unsuccessful for common, later-onset traits with complex multifactorial aetiologies, with notable exceptions.
“Efforts to apply the approach–linkage analysis in multiplex pedigrees–that had been so successful for the high-penetrance variants responsible for Mendelian disease were, with notable exceptions34–36, largely unsuccessful for common, later-onset traits with more complex multifactorial aetiologies, such as asthma, diabetes and depression.”
From A brief history of human disease genetics (2020) · cites this paper as [36]
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Sequential tests for the detection of linkage.
Morton, N. E. (1955) · PubMed · Cited by 1,590 · see citing works
Ott, J. (1974) · PubMed · Cited by 1,028 · see citing works
Genetics of Juvenile Diabetes Mellitus
Rubinstein, P., Suciu‐Foca, N., & Nicholson, J. F. (1977) · New England Journal of Medicine · doi:10.1056/nejm197711102971905 · Cited by 122 · see citing works
The Histocompatibility System in Juvenile, Insulin-Dependent Diabetic Multiplex Kindreds
Barbosa, J. J., King, R., Noreen, H. J., et al. (1977) · Journal of Clinical Investigation · doi:10.1172/jci108879 · Cited by 98 · see citing works
Self-citationHISTOCOMPATIBILITY ANTIGENS IN DIABETIC IDENTICAL TWINS
Nelson, P. G., Pyke, D. A., Cudworth, A. G., et al. (1975) · The Lancet · doi:10.1016/s0140-6736(75)90668-6 · Cited by 71 · see citing works
Segregation Analysis of Juvenile Diabetes Mellitus
Barrai, I., & Cann, H. M. (1965) · Journal of Medical Genetics · doi:10.1136/jmg.2.1.8 · Cited by 28 · see citing works
Barbosa, J., Noreen, H., King, R., et al. (1978) · New England Journal of Medicine · doi:10.1056/nejm197802232980824 · Cited by 8 · see citing works
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A brief history of human disease genetics
Claussnitzer, M., Cho, J. H., Collins, R., Cox, N. J., Dermitzakis, E. T., Hurles, M. E., Kathiresan, S., Kenny, E. E., Lindgren, C. M., MacArthur, D. G., et al. (2020) · Nature · doi:10.1038/s41586-019-1879-7 · Cited by 697 · see citing works
- Authors
- Barbosa, J., Chern, M. M., Noreen, H., & Anderson, V. E.
- Affiliations
- University of Minnesota (US)
- Venue
- Journal of Clinical Investigation
- Published
- 1978-08-01
- Volume
- 62
- Issue
- 2
- Pages
- 492-495
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC371788
- OpenAlex
- W2001275025
- Cited by
- 53
- References
- 7
- Citations by year
- 2020: 1 · 2015: 1
- FWCI
- 9.24
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- HLA, type 1 diabetes, genetic linkage, multiplex families, autosomal recessive inheritance, penetrance, lod score, recombination frequency, ascertainment bias
- MeSH terms
- Diabetes Mellitus, Type 1, Genotype, HLA Antigens, Humans, Insulin, Genetic Linkage
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