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. 1989 Apr;26(4):255–259. doi: 10.1136/jmg.26.4.255

Haplotypes identified by 10 DNA restriction fragment length polymorphisms at the human low density lipoprotein receptor gene locus.

M J Kotze 1, E Langenhoven 1, A E Retief 1, H C Seftel 1, H E Henderson 1, H F Weich 1
PMCID: PMC1017299  PMID: 2565980

Abstract

Ten useful two allele restriction fragment length polymorphisms of the low density lipoprotein receptor gene were used for haplotype analysis in 45 unrelated familial hypercholesterolaemic (FH) patients, 60 normal controls, and 32 FH homozygotes, all of whom were white Afrikaners. Pedigree analysis in 27 informative heterozygous FH and 23 normal families has shown the segregation of at least 17 haplotypes in the normal population (111 chromosomes) compared to a predominant association of two of these haplotypes with the disease in the FH subjects. This association was further confirmed in 32 FH homozygotes, indicating at least two 'founder' members for the disease in the Afrikaner population. Recombination events were not detected in any of the families studied and we thus conclude that the haplotypes associated with FH function as specific markers for the disease and will allow presymptomatic diagnosis in affected families.

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Selected References

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

  1. Antonarakis S. E., Boehm C. D., Giardina P. J., Kazazian H. H., Jr Nonrandom association of polymorphic restriction sites in the beta-globin gene cluster. Proc Natl Acad Sci U S A. 1982 Jan;79(1):137–141. doi: 10.1073/pnas.79.1.137. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Brown M. S., Goldstein J. L. A receptor-mediated pathway for cholesterol homeostasis. Science. 1986 Apr 4;232(4746):34–47. doi: 10.1126/science.3513311. [DOI] [PubMed] [Google Scholar]
  3. Funke H., Klug J., Frossard P., Coleman R., Assmann G. Pst I RFLP close to the LDL receptor gene. Nucleic Acids Res. 1986 Oct 10;14(19):7820–7820. doi: 10.1093/nar/14.19.7820. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Geisel J., Weisshaar B., Oette K., Mechtel M., Doerfler W. Double Msp I RFLP in the human LDL receptor gene. Nucleic Acids Res. 1987 May 11;15(9):3943–3943. doi: 10.1093/nar/15.9.3943. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Hobbs H. H., Esser V., Russell D. W. AvaII polymorphism in the human LDL receptor gene. Nucleic Acids Res. 1987 Jan 12;15(1):379–379. doi: 10.1093/nar/15.1.379. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Humphries S. E., Kessling A. M., Horsthemke B., Donald J. A., Seed M., Jowett N., Holm M., Galton D. J., Wynn V., Williamson R. A common DNA polymorphism of the low-density lipoprotein (LDL) receptor gene and its use in diagnosis. Lancet. 1985 May 4;1(8436):1003–1005. doi: 10.1016/s0140-6736(85)91611-3. [DOI] [PubMed] [Google Scholar]
  7. Jooste P. L., Benadé A. J., Rossouw J. E. Prevalence of familial hypercholesterolaemia in three rural South African communities. S Afr Med J. 1986 Apr 26;69(9):548–551. [PubMed] [Google Scholar]
  8. Kotze M. J., Langenhoven E., Dietzsch E., Retief A. E. A RFLP associated with the low-density lipoprotein receptor gene (LDLR). Nucleic Acids Res. 1987 Jan 12;15(1):376–376. doi: 10.1093/nar/15.1.376. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Kotze M. J., Langenhoven E., Retief A. E. Improved visualization of the Bst EII RFLP of the human LDL receptor gene by co-digestion. Nucleic Acids Res. 1987 Dec 10;15(23):10067–10067. doi: 10.1093/nar/15.23.10067. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kotze M. J., Langenhoven E., Retief A. E., Steyn K., Marais M. P., Grobbelaar J. J., Oosthuizen C. J., Weich H. F., Benadé A. J. Haplotype associations of three DNA polymorphisms at the human low density lipoprotein receptor gene locus in familial hypercholesterolaemia. J Med Genet. 1987 Dec;24(12):750–755. doi: 10.1136/jmg.24.12.750. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kotze M. J., Retief A. E., Brink P. A., Weich H. F. A DNA polymorphism in the human low-density lipoprotein receptor gene. S Afr Med J. 1986 Jul 19;70(2):77–79. [PubMed] [Google Scholar]
  12. Leitersdorf E., Hobbs H. H. Human LDL receptor gene: two ApaLI RFLPs. Nucleic Acids Res. 1987 Mar 25;15(6):2782–2782. doi: 10.1093/nar/15.6.2782. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Seftel H. C., Baker S. G., Sandler M. P., Forman M. B., Joffe B. I., Mendelsohn D., Jenkins T., Mieny C. J. A host of hypercholesterolaemic homozygotes in South Africa. Br Med J. 1980 Sep 6;281(6241):633–636. doi: 10.1136/bmj.281.6241.633. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Steyn L. T., Pretorius A., Brink P. A., Bester A. J. RFLP for the human LDL receptor gene (LDLR): Bst EII. Nucleic Acids Res. 1987 Jun 11;15(11):4702–4702. doi: 10.1093/nar/15.11.4702. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Südhof T. C., Goldstein J. L., Brown M. S., Russell D. W. The LDL receptor gene: a mosaic of exons shared with different proteins. Science. 1985 May 17;228(4701):815–822. doi: 10.1126/science.2988123. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Yamakawa K., Okafuji T., Iwamura Y., Russell D. W., Hamaguchi H. TaqI polymorphism in the human LDL receptor gene. Nucleic Acids Res. 1987 Sep 25;15(18):7659–7659. doi: 10.1093/nar/15.18.7659. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Yamamoto T., Davis C. G., Brown M. S., Schneider W. J., Casey M. L., Goldstein J. L., Russell D. W. The human LDL receptor: a cysteine-rich protein with multiple Alu sequences in its mRNA. Cell. 1984 Nov;39(1):27–38. doi: 10.1016/0092-8674(84)90188-0. [DOI] [PubMed] [Google Scholar]

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