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. 1995 Jan;56(1):248–253.

Refining the localization of the PKD2 locus on chromosome 4q by linkage analysis in Spanish families with autosomal dominant polycystic kidney disease type 2.

J L San Millán 1, M Viribay 1, B Peral 1, I Martínez 1, J Weissenbach 1, F Moreno 1
PMCID: PMC1801339  PMID: 7825585

Abstract

Autosomal dominant polycystic kidney disease (ADPKD) is a genetically heterogeneous disorder. At least two distinct forms of ADPKD are now well defined. In approximately 86% of affected European families, a gene defect localized to 16p13.3 was responsible for ADPKD, while a second locus has been recently localized to 4q13-q23 as candidate for the disease in the remaining families. We present confirmation of linkage to microsatellite markers on chromosome 4q in eight Spanish families with ADPKD, in which the disease was not linked to 16p13.3. By linkage analysis with marker D4S423, a maximum lod score of 9.03 at a recombination fraction of .00 was obtained. Multipoint linkage analysis, as well as a study of recombinant haplotypes, placed the PKD2 locus between D4S1542 and D4S1563, thereby defining a genetic interval of approximately 1 cM. The refined map will serve as a genetic framework for additional genetic and physical mapping of the region and will improve the accuracy of presymptomatic diagnosis of PKD2.

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Selected References

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  1. Bear J. C., McManamon P., Morgan J., Payne R. H., Lewis H., Gault M. H., Churchill D. N. Age at clinical onset and at ultrasonographic detection of adult polycystic kidney disease: data for genetic counselling. Am J Med Genet. 1984 May;18(1):45–53. doi: 10.1002/ajmg.1320180108. [DOI] [PubMed] [Google Scholar]
  2. Bear J. C., Parfrey P. S., Morgan J. M., Martin C. J., Cramer B. C. Autosomal dominant polycystic kidney disease: new information for genetic counselling. Am J Med Genet. 1992 Jun 1;43(3):548–553. doi: 10.1002/ajmg.1320430309. [DOI] [PubMed] [Google Scholar]
  3. Breuning M. H., Snijdewint F. G., Brunner H., Verwest A., Ijdo J. W., Saris J. J., Dauwerse J. G., Blonden L., Keith T., Callen D. F. Map of 16 polymorphic loci on the short arm of chromosome 16 close to the polycystic kidney disease gene (PKD1). J Med Genet. 1990 Oct;27(10):603–613. doi: 10.1136/jmg.27.10.603. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Brissenden J. E., Roscoe J. M., Simpson N. E., Silverman M. Linkage exclusion between the autosomal dominant polycystic kidney disease locus and chromosome 16 markers in a new family. J Am Soc Nephrol. 1991 Oct;2(4):913–919. doi: 10.1681/ASN.V24913. [DOI] [PubMed] [Google Scholar]
  5. DALGAARD O. Z. Bilateral polycystic disease of the kidneys; a follow-up of two hundred and eighty-four patients and their families. Acta Med Scand Suppl. 1957;328:1–255. [PubMed] [Google Scholar]
  6. Fenton I., Sandkuijl L. A. MEGABASE/PKD: a genetic database for polycystic kidney disease. Contrib Nephrol. 1992;97:118–127. doi: 10.1159/000421650. [DOI] [PubMed] [Google Scholar]
  7. Fossdal R., Böthvarsson M., Asmundsson P., Ragnarsson J., Peters D., Breuning M. H., Jensson O. Icelandic families with autosomal dominant polycystic kidney disease: families unlinked to chromosome 16p13.3 revealed by linkage analysis. Hum Genet. 1993 Jul;91(6):609–613. doi: 10.1007/BF00205089. [DOI] [PubMed] [Google Scholar]
  8. Gabow P. A., Johnson A. M., Kaehny W. D., Kimberling W. J., Lezotte D. C., Duley I. T., Jones R. H. Factors affecting the progression of renal disease in autosomal-dominant polycystic kidney disease. Kidney Int. 1992 May;41(5):1311–1319. doi: 10.1038/ki.1992.195. [DOI] [PubMed] [Google Scholar]
  9. Gyapay G., Morissette J., Vignal A., Dib C., Fizames C., Millasseau P., Marc S., Bernardi G., Lathrop M., Weissenbach J. The 1993-94 Généthon human genetic linkage map. Nat Genet. 1994 Jun;7(2 Spec No):246–339. doi: 10.1038/ng0694supp-246. [DOI] [PubMed] [Google Scholar]
  10. Harris P. C., Thomas S., Ratcliffe P. J., Breuning M. H., Coto E., Lopez-Larrea C. Rapid genetic analysis of families with polycystic kidney disease 1 by means of a microsatellite marker. Lancet. 1991 Dec 14;338(8781):1484–1487. doi: 10.1016/0140-6736(91)92300-q. [DOI] [PubMed] [Google Scholar]
  11. Kimberling W. J., Fain P. R., Kenyon J. B., Goldgar D., Sujansky E., Gabow P. A. Linkage heterogeneity of autosomal dominant polycystic kidney disease. N Engl J Med. 1988 Oct 6;319(14):913–918. doi: 10.1056/NEJM198810063191405. [DOI] [PubMed] [Google Scholar]
  12. Kimberling W. J., Kumar S., Gabow P. A., Kenyon J. B., Connolly C. J., Somlo S. Autosomal dominant polycystic kidney disease: localization of the second gene to chromosome 4q13-q23. Genomics. 1993 Dec;18(3):467–472. doi: 10.1016/s0888-7543(11)80001-7. [DOI] [PubMed] [Google Scholar]
  13. Lathrop G. M., Lalouel J. M. Easy calculations of lod scores and genetic risks on small computers. Am J Hum Genet. 1984 Mar;36(2):460–465. [PMC free article] [PubMed] [Google Scholar]
  14. Mills K. A., Buetow K. H., Xu Y., Weber J. L., Altherr M. R., Wasmuth J. J., Murray J. C. Genetic and physical maps of human chromosome 4 based on dinucleotide repeats. Genomics. 1992 Oct;14(2):209–219. doi: 10.1016/s0888-7543(05)80208-3. [DOI] [PubMed] [Google Scholar]
  15. Peral B., San Millán J. L., Hernández C., Valero A., Lathrop G. M., Beckmann J. S., Moreno F. Estimating locus heterogeneity in autosomal dominant polycystic kidney disease (ADPKD) in the Spanish population. J Med Genet. 1993 Nov;30(11):910–913. doi: 10.1136/jmg.30.11.910. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Peral B., Ward C. J., San Millán J. L., Thomas S., Stallings R. L., Moreno F., Harris P. C. Evidence of linkage disequilibrium in the Spanish polycystic kidney disease I population. Am J Hum Genet. 1994 May;54(5):899–908. [PMC free article] [PubMed] [Google Scholar]
  17. Peters D. J., Spruit L., Saris J. J., Ravine D., Sandkuijl L. A., Fossdal R., Boersma J., van Eijk R., Nørby S., Constantinou-Deltas C. D. Chromosome 4 localization of a second gene for autosomal dominant polycystic kidney disease. Nat Genet. 1993 Dec;5(4):359–362. doi: 10.1038/ng1293-359. [DOI] [PubMed] [Google Scholar]
  18. Ravine D., Walker R. G., Gibson R. N., Forrest S. M., Richards R. I., Friend K., Sheffield L. J., Kincaid-Smith P., Danks D. M. Phenotype and genotype heterogeneity in autosomal dominant polycystic kidney disease. Lancet. 1992 Nov 28;340(8831):1330–1333. doi: 10.1016/0140-6736(92)92503-8. [DOI] [PubMed] [Google Scholar]
  19. Reeders S. T., Breuning M. H., Davies K. E., Nicholls R. D., Jarman A. P., Higgs D. R., Pearson P. L., Weatherall D. J. A highly polymorphic DNA marker linked to adult polycystic kidney disease on chromosome 16. Nature. 1985 Oct 10;317(6037):542–544. doi: 10.1038/317542a0. [DOI] [PubMed] [Google Scholar]
  20. Romeo G., Devoto M., Costa G., Roncuzzi L., Catizone L., Zucchelli P., Germino G. G., Keith T., Weatherall D. J., Reeders S. T. A second genetic locus for autosomal dominant polycystic kidney disease. Lancet. 1988 Jul 2;2(8601):8–11. doi: 10.1016/s0140-6736(88)92943-1. [DOI] [PubMed] [Google Scholar]

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