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. 1997 Jun;60(6):1461–1467. doi: 10.1086/515469

Homozygosity and linkage-disequilibrium mapping of the urofacial (Ochoa) syndrome gene to a 1-cM interval on chromosome 10q23-q24.

C Y Wang 1, B Hawkins-Lee 1, B Ochoa 1, R D Walker 1, J X She 1
PMCID: PMC1716147  PMID: 9199567

Abstract

The urofacial (Ochoa) syndrome (UFS) is a rare autosomal recessive disease characterized by congenital obstructive uropathy and abnormal facial expression. The patients present with enuresis, urinary-tract infection, hydronephrosis, and voiding dysfunctions as a result of neurogenic bladders. To map the UFS gene, a genome screen using a combination of homozygosity-mapping and DNA-pooling strategies was performed in 20 selected patients, one patient pool, and three control pools (unaffected relatives). After analyses of 36 randomly chosen markers, D10S677 was identified as being linked to and associated with UFS, as suggested by a significant excess of homozygosity in patients compared with that in unaffected relatives (P < 10(-6)), as well as by the allelic-frequency differences between the patient pool and control pools. Ten additional markers flanking D10S677 and covering a 22-cM region then were analyzed to fine-map the UFS gene by use of haplotype (linkage disequilibrium) analysis. All 31 patients were found to be homozygous for two closely linked markers (D10S1726 and D10S198) located approximately 5 cM telomeric to D10S677, whereas only 12% of the unaffected relatives were homozygous for both markers (P < 10(-19)). Several patients are heterozygous at two markers immediately flanking D10S1726/D10S198, one on the centromeric side (D10S1433) and the other on the telomeric side (D10S603). These recombinational events place the UFS gene near D10S1726/D10S198 and within a 1-cM interval defined by D10S1433 and D10S603 on chromosome 10q23-q24.

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Selected References

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  1. Arnheim N., Strange C., Erlich H. Use of pooled DNA samples to detect linkage disequilibrium of polymorphic restriction fragments and human disease: studies of the HLA class II loci. Proc Natl Acad Sci U S A. 1985 Oct;82(20):6970–6974. doi: 10.1073/pnas.82.20.6970. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Buetow K. H., Weber J. L., Ludwigsen S., Scherpbier-Heddema T., Duyk G. M., Sheffield V. C., Wang Z., Murray J. C. Integrated human genome-wide maps constructed using the CEPH reference panel. Nat Genet. 1994 Apr;6(4):391–393. doi: 10.1038/ng0494-391. [DOI] [PubMed] [Google Scholar]
  3. Carmi R., Rokhlina T., Kwitek-Black A. E., Elbedour K., Nishimura D., Stone E. M., Sheffield V. C. Use of a DNA pooling strategy to identify a human obesity syndrome locus on chromosome 15. Hum Mol Genet. 1995 Jan;4(1):9–13. doi: 10.1093/hmg/4.1.9. [DOI] [PubMed] [Google Scholar]
  4. Darvasi A., Soller M. Selective DNA pooling for determination of linkage between a molecular marker and a quantitative trait locus. Genetics. 1994 Dec;138(4):1365–1373. doi: 10.1093/genetics/138.4.1365. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Dib C., Fauré S., Fizames C., Samson D., Drouot N., Vignal A., Millasseau P., Marc S., Hazan J., Seboun E. A comprehensive genetic map of the human genome based on 5,264 microsatellites. Nature. 1996 Mar 14;380(6570):152–154. doi: 10.1038/380152a0. [DOI] [PubMed] [Google Scholar]
  6. Fukai K., Oh J., Karim M. A., Moore K. J., Kandil H. H., Ito H., Bürger J., Spritz R. A. Homozygosity mapping of the gene for Chediak-Higashi syndrome to chromosome 1q42-q44 in a segment of conserved synteny that includes the mouse beige locus (bg). Am J Hum Genet. 1996 Sep;59(3):620–624. [PMC free article] [PubMed] [Google Scholar]
  7. Gelb B. D., Edelson J. G., Desnick R. J. Linkage of pycnodysostosis to chromosome 1q21 by homozygosity mapping. Nat Genet. 1995 Jun;10(2):235–237. doi: 10.1038/ng0695-235. [DOI] [PubMed] [Google Scholar]
  8. German J., Roe A. M., Leppert M. F., Ellis N. A. Bloom syndrome: an analysis of consanguineous families assigns the locus mutated to chromosome band 15q26.1. Proc Natl Acad Sci U S A. 1994 Jul 5;91(14):6669–6673. doi: 10.1073/pnas.91.14.6669. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gschwend M., Levran O., Kruglyak L., Ranade K., Verlander P. C., Shen S., Faure S., Weissenbach J., Altay C., Lander E. S. A locus for Fanconi anemia on 16q determined by homozygosity mapping. Am J Hum Genet. 1996 Aug;59(2):377–384. [PMC free article] [PubMed] [Google Scholar]
  10. Khatib H., Darvasi A., Plotski Y., Soller M. Determining relative microsatellite allele frequencies in pooled DNA samples. PCR Methods Appl. 1994 Aug;4(1):13–18. doi: 10.1101/gr.4.1.13. [DOI] [PubMed] [Google Scholar]
  11. Lander E. S., Botstein D. Homozygosity mapping: a way to map human recessive traits with the DNA of inbred children. Science. 1987 Jun 19;236(4808):1567–1570. doi: 10.1126/science.2884728. [DOI] [PubMed] [Google Scholar]
  12. LeGuern E., Guilbot A., Kessali M., Ravisé N., Tassin J., Maisonobe T., Grid D., Brice A. Homozygosity mapping of an autosomal recessive form of demyelinating Charcot-Marie-Tooth disease to chromosome 5q23-q33. Hum Mol Genet. 1996 Oct;5(10):1685–1688. doi: 10.1093/hmg/5.10.1685. [DOI] [PubMed] [Google Scholar]
  13. Luo D. F., Bui M. M., Muir A., Maclaren N. K., Thomson G., She J. X. Affected-sib-pair mapping of a novel susceptibility gene to insulin-dependent diabetes mellitus (IDDM8) on chromosome 6q25-q27. Am J Hum Genet. 1995 Oct;57(4):911–919. [PMC free article] [PubMed] [Google Scholar]
  14. Luo D. F., Buzzetti R., Rotter J. I., Maclaren N. K., Raffel L. J., Nisticò L., Giovannini C., Pozzilli P., Thomson G., She J. X. Confirmation of three susceptibility genes to insulin-dependent diabetes mellitus: IDDM4, IDDM5 and IDDM8. Hum Mol Genet. 1996 May;5(5):693–698. doi: 10.1093/hmg/5.5.693. [DOI] [PubMed] [Google Scholar]
  15. Luo D. F., Maclaren N. K., Huang H. S., Muir A., She J. X. Intrafamilial and case-control association analysis of D2S152 in insulin-dependent diabetes. Autoimmunity. 1995;21(2):143–147. doi: 10.3109/08916939508993363. [DOI] [PubMed] [Google Scholar]
  16. Ochoa B., Gorlin R. J. Urofacial (ochoa) syndrome. Am J Med Genet. 1987 Jul;27(3):661–667. doi: 10.1002/ajmg.1320270320. [DOI] [PubMed] [Google Scholar]
  17. Ochoa B. The urofacial (Ochoa) syndrome revisited. J Urol. 1992 Aug;148(2 Pt 2):580–583. doi: 10.1016/s0022-5347(17)36659-4. [DOI] [PubMed] [Google Scholar]
  18. Pacek P., Sajantila A., Syvänen A. C. Determination of allele frequencies at loci with length polymorphism by quantitative analysis of DNA amplified from pooled samples. PCR Methods Appl. 1993 May;2(4):313–317. doi: 10.1101/gr.2.4.313. [DOI] [PubMed] [Google Scholar]
  19. Pollak M. R., Chou Y. H., Cerda J. J., Steinmann B., La Du B. N., Seidman J. G., Seidman C. E. Homozygosity mapping of the gene for alkaptonuria to chromosome 3q2. Nat Genet. 1993 Oct;5(2):201–204. doi: 10.1038/ng1093-201. [DOI] [PubMed] [Google Scholar]
  20. Sheffield V. C., Nishimura D. Y., Stone E. M. Novel approaches to linkage mapping. Curr Opin Genet Dev. 1995 Jun;5(3):335–341. doi: 10.1016/0959-437x(95)80048-4. [DOI] [PubMed] [Google Scholar]
  21. Sheffield V. C., Weber J. L., Buetow K. H., Murray J. C., Even D. A., Wiles K., Gastier J. M., Pulido J. C., Yandava C., Sunden S. L. A collection of tri- and tetranucleotide repeat markers used to generate high quality, high resolution human genome-wide linkage maps. Hum Mol Genet. 1995 Oct;4(10):1837–1844. doi: 10.1093/hmg/4.10.1837. [DOI] [PubMed] [Google Scholar]
  22. Taylor B. A., Navin A., Phillips S. J. PCR-amplification of simple sequence repeat variants from pooled DNA samples for rapidly mapping new mutations of the mouse. Genomics. 1994 Jun;21(3):626–632. doi: 10.1006/geno.1994.1323. [DOI] [PubMed] [Google Scholar]
  23. Teebi A. S., Farag T. I., el-Khalifa M. Y., Besisso M. S., al-Ansari A. G. Urofacial syndrome. Am J Med Genet. 1989 Dec;34(4):608–608. doi: 10.1002/ajmg.1320340432. [DOI] [PubMed] [Google Scholar]
  24. Teebi A. S., Hassoon M. M. Urofacial syndrome associated with hydrocephalus due to aqueductal stenosis. Am J Med Genet. 1991 Aug 1;40(2):199–200. doi: 10.1002/ajmg.1320400215. [DOI] [PubMed] [Google Scholar]
  25. Thomas P. M., Cote G. J., Hallman D. M., Mathew P. M. Homozygosity mapping, to chromosome 11p, of the gene for familial persistent hyperinsulinemic hypoglycemia of infancy. Am J Hum Genet. 1995 Feb;56(2):416–421. [PMC free article] [PubMed] [Google Scholar]
  26. Wayne S., Der Kaloustian V. M., Schloss M., Polomeno R., Scott D. A., Hejtmancik J. F., Sheffield V. C., Smith R. J. Localization of the Usher syndrome type ID gene (Ush1D) to chromosome 10. Hum Mol Genet. 1996 Oct;5(10):1689–1692. doi: 10.1093/hmg/5.10.1689. [DOI] [PubMed] [Google Scholar]
  27. Williams J. G., Reiter R. S., Young R. M., Scolnik P. A. Genetic mapping of mutations using phenotypic pools and mapped RAPD markers. Nucleic Acids Res. 1993 Jun 11;21(11):2697–2702. doi: 10.1093/nar/21.11.2697. [DOI] [PMC free article] [PubMed] [Google Scholar]

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