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. 1988 Oct;43(4):495–501.

Linkage disequilibrium in the human insulin/insulin-like growth factor II region of human chromosome II.

N J Cox 1, G I Bell 1, K S Xiang 1
PMCID: PMC1715486  PMID: 2902788

Abstract

Caucasian (N = 128) and Chinese (N = 84) subjects were typed for RFLPs in the insulin (INS)/insulin-like growth factor II (IGF2) region of chromosome 11. Both the analysis of extended haplotypes and the pairwise measures of linkage disequilibrium among the RFLPs indicate that there is extensive linkage disequilibrium in the INS/IGF2 region. The disequilibrium extends across the hypervariable region (HVR) located just 5' to the INS gene and encompasses a region of at least 40 kbp. Previous studies had suggested that linkage disequilibrium in the INS region was negligible and that this region may therefore contain a "recombinational hotspot" (Chakravarti et al. 1986). However, results of this and another recent study (Thompson et al. 1988) highlight the importance of the frequencies of associated alleles in the ability to detect linkage disequilibrium. Thus, the previous failure to detect disequilibrium in the INS region may have reflected a lack of power, rather than a true absence of disequilibrium in this region.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bell G. I., Gerhard D. S., Fong N. M., Sanchez-Pescador R., Rall L. B. Isolation of the human insulin-like growth factor genes: insulin-like growth factor II and insulin genes are contiguous. Proc Natl Acad Sci U S A. 1985 Oct;82(19):6450–6454. doi: 10.1073/pnas.82.19.6450. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bell G. I., Horita S., Karam J. H. A polymorphic locus near the human insulin gene is associated with insulin-dependent diabetes mellitus. Diabetes. 1984 Feb;33(2):176–183. doi: 10.2337/diab.33.2.176. [DOI] [PubMed] [Google Scholar]
  3. Bell G. I., Karam J. H., Rutter W. J. Polymorphic DNA region adjacent to the 5' end of the human insulin gene. Proc Natl Acad Sci U S A. 1981 Sep;78(9):5759–5763. doi: 10.1073/pnas.78.9.5759. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Brown A. H. Sample sizes required to detect linkage disequilibrium between two or three loci. Theor Popul Biol. 1975 Oct;8(2):184–201. doi: 10.1016/0040-5809(75)90031-3. [DOI] [PubMed] [Google Scholar]
  5. Chakravarti A., Elbein S. C., Permutt M. A. Evidence for increased recombination near the human insulin gene: implication for disease association studies. Proc Natl Acad Sci U S A. 1986 Feb;83(4):1045–1049. doi: 10.1073/pnas.83.4.1045. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Egeland J. A., Gerhard D. S., Pauls D. L., Sussex J. N., Kidd K. K., Allen C. R., Hostetter A. M., Housman D. E. Bipolar affective disorders linked to DNA markers on chromosome 11. 1987 Feb 26-Mar 4Nature. 325(6107):783–787. doi: 10.1038/325783a0. [DOI] [PubMed] [Google Scholar]
  7. Fukumoto H., Seino S., Imura H., Seino Y., Bell G. I. Characterization and expression of human HepG2/erythrocyte glucose-transporter gene. Diabetes. 1988 May;37(5):657–661. doi: 10.2337/diab.37.5.657. [DOI] [PubMed] [Google Scholar]
  8. Hedrick P. W. Gametic disequilibrium measures: proceed with caution. Genetics. 1987 Oct;117(2):331–341. doi: 10.1093/genetics/117.2.331. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Jowett N. I., Williams L. G., Hitman G. A., Galton D. J. Diabetic hypertriglyceridaemia and related 5' flanking polymorphism of the human insulin gene. Br Med J (Clin Res Ed) 1984 Jan 14;288(6411):96–99. doi: 10.1136/bmj.288.6411.96. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Lewontin R C. The Interaction of Selection and Linkage. I. General Considerations; Heterotic Models. Genetics. 1964 Jan;49(1):49–67. doi: 10.1093/genetics/49.1.49. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. MacLean C. J., Morton N. E. Estimation of myriad haplotype frequencies. Genet Epidemiol. 1985;2(3):263–272. doi: 10.1002/gepi.1370020304. [DOI] [PubMed] [Google Scholar]
  12. Mandrup-Poulsen T., Owerbach D., Mortensen S. A., Johansen K., Meinertz H., Sørensen H., Nerup J. DNA sequences flanking the insulin gene on chromosome 11 confer risk of atherosclerosis. Lancet. 1984 Feb 4;1(8371):250–252. doi: 10.1016/s0140-6736(84)90126-0. [DOI] [PubMed] [Google Scholar]
  13. Thompson E. A., Deeb S., Walker D., Motulsky A. G. The detection of linkage disequilibrium between closely linked markers: RFLPs at the AI-CIII apolipoprotein genes. Am J Hum Genet. 1988 Jan;42(1):113–124. [PMC free article] [PubMed] [Google Scholar]
  14. Xiang K., Cox N. J., Bell G. I. Apa I and Sst I RFLPs at the insulin-like growth factor II (IGF2) locus on chromosome 11. Nucleic Acids Res. 1988 Apr 25;16(8):3599–3599. doi: 10.1093/nar/16.8.3599. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Xiang K., Karam J. H., Bell G. I. BamHI RFLP at the insulin-like growth factor II (IGF2) locus on chromosome 11. Nucleic Acids Res. 1987 Sep 25;15(18):7655–7655. doi: 10.1093/nar/15.18.7655. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. de Pagter-Holthuizen P., Jansen M., van Schaik F. M., van der Kammen R., Oosterwijk C., Van den Brande J. L., Sussenbach J. S. The human insulin-like growth factor II gene contains two development-specific promoters. FEBS Lett. 1987 Apr 20;214(2):259–264. doi: 10.1016/0014-5793(87)80066-2. [DOI] [PubMed] [Google Scholar]

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