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. 1996 Jul;33(7):590–593. doi: 10.1136/jmg.33.7.590

Linkage disequilibrium between four intragenic polymorphic microsatellites of the NF1 gene and its implications for genetic counselling.

M C Valero 1, E Velasco 1, A Valero 1, F Moreno 1, C Hernández-Chico 1
PMCID: PMC1050668  PMID: 8818946

Abstract

Four intragenic polymorphic microsatellite markers, AAAT Alu repeat, IVS27AC28.4, ACI27.2, and IVS38GT53.0, located along a 65 kb DNA region of the NF1 gene, were used to genotype 64 Spanish families with neurofibromatosis type 1 (NF1). Linkage disequilirium between each pair of markers was evaluated. Three of these markers, AAAT Alu repeat, ACI27.2, and IVS38GT53.0, exhibit linkage disequilibrium between each other. Analysis of extended haplotypes provides further evidence of the disequilibrium within this region since only 11 haplotypes account for 52% of the total chromosomes. Because of linkage disequilibrium, the informativeness of marker combinations for genotyping of NF1 families is diminished. There was no difference in the overall distribution of alleles between affected and normal chromosomes. An at risk haplotype was not found, as expected for a disease with at least 50% of cases being sporadic.

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Selected References

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

  1. 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]
  2. Chakravarti A., Buetow K. H., Antonarakis S. E., Waber P. G., Boehm C. D., Kazazian H. H. Nonuniform recombination within the human beta-globin gene cluster. Am J Hum Genet. 1984 Nov;36(6):1239–1258. [PMC free article] [PubMed] [Google Scholar]
  3. Jorde L. B., Watkins W. S., Viskochil D., O'Connell P., Ward K. Linkage disequilibrium in the neurofibromatosis 1 (NF1) region: implications for gene mapping. Am J Hum Genet. 1993 Nov;53(5):1038–1050. [PMC free article] [PubMed] [Google Scholar]
  4. Li Y., O'Connell P., Breidenbach H. H., Cawthon R., Stevens J., Xu G., Neil S., Robertson M., White R., Viskochil D. Genomic organization of the neurofibromatosis 1 gene (NF1). Genomics. 1995 Jan 1;25(1):9–18. doi: 10.1016/0888-7543(95)80104-t. [DOI] [PubMed] [Google Scholar]
  5. Lázaro C., Gaona A., Estivill X. Two CA/GT repeat polymorphisms in intron 27 of the human neurofibromatosis (NF1) gene. Hum Genet. 1994 Mar;93(3):351–352. doi: 10.1007/BF00212039. [DOI] [PubMed] [Google Scholar]
  6. Lázaro C., Gaona A., Ravella A., Volpini V., Casals T., Fuentes J. J., Estivill X. Novel alleles, hemizygosity and deletions at an Alu-repeat within the neurofibromatosis type 1 (NF1) gene. Hum Mol Genet. 1993 Jun;2(6):725–730. doi: 10.1093/hmg/2.6.725. [DOI] [PubMed] [Google Scholar]
  7. Lázaro C., Gaona A., Xu G., Weiss R., Estivill X. A highly informative CA/GT repeat polymorphism in intron 38 of the human neurofibromatosis type 1 (NF1) gene. Hum Genet. 1993 Oct;92(4):429–430. doi: 10.1007/BF01247353. [DOI] [PubMed] [Google Scholar]
  8. Messiaen L., De Bie S., Moens T., Van den Enden A., Leroy J. Lack of independence between five DNA polymorphisms in the NF1 gene. Hum Mol Genet. 1993 Apr;2(4):485–485. doi: 10.1093/hmg/2.4.485. [DOI] [PubMed] [Google Scholar]
  9. Miserez A. R., Schuster H., Chiodetti N., Keller U. Polymorphic haplotypes and recombination rates at the LDL receptor gene locus in subjects with and without familial hypercholesterolemia who are from different populations. Am J Hum Genet. 1993 Apr;52(4):808–826. [PMC free article] [PubMed] [Google Scholar]
  10. Myers R. M., Maniatis T., Lerman L. S. Detection and localization of single base changes by denaturing gradient gel electrophoresis. Methods Enzymol. 1987;155:501–527. doi: 10.1016/0076-6879(87)55033-9. [DOI] [PubMed] [Google Scholar]
  11. Ward K., O'Connell P., Carey J. C., Leppert M., Jolley S., Plaetke R., Ogden B., White R. Diagnosis of neurofibromatosis I by using tightly linked, flanking DNA markers. Am J Hum Genet. 1990 May;46(5):943–949. [PMC free article] [PubMed] [Google Scholar]
  12. Weber J. L., Wong C. Mutation of human short tandem repeats. Hum Mol Genet. 1993 Aug;2(8):1123–1128. doi: 10.1093/hmg/2.8.1123. [DOI] [PubMed] [Google Scholar]
  13. Xu G. F., Nelson L., O'Connell P., White R. An Alu polymorphism intragenic to the neurofibromatosis type 1 gene (NF1). Nucleic Acids Res. 1991 Jul 11;19(13):3764–3764. doi: 10.1093/nar/19.13.3764. [DOI] [PMC free article] [PubMed] [Google Scholar]

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