Abstract
Various polymorphic markers with a random distribution along the X chromosome were used in a linkage analysis performed on a family with apparently Xlinked recessive inheritance of neural tube defects (NTD). The lod score values were used to generate an exclusion map of the X chromosome; this showed that the responsible gene was probably not located in the middle part of Xp or in the distal region of Xq. A further refining of these results was achieved by haplotype analysis, which indicated that the gene for X-linked NTD was located either within Xp21.1-pter, distal from the DMD locus, or in the region Xq12–q24 between DXS106 and DXS424. Multipoint linkage analysis revealed that the likelihood for gene location is highest for the region on Xp. The region Xq26–q28, which has syntenic homology with the segment of the murine X chromosome carrying the locus for ‘bent tail’ (Bn), a mouse model for X-linked NTD, is excluded as the location for the gene underlying X-linked NTD in the present family. Thus, the human homologue of the Bn gene and the present defective gene are not identical, suggesting that more than one gene on the X chromosome plays a role in the development of the neural tube.
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References
Allen RC, Belmont JW (1992) Dinucleotide repeat polymorphism at the locus DXS178. Hum Mol Genet 1:216
Baraitser M, Burn J (1984) Neural tube defects as an X-linked condition. Am J Med Genet 17:383–385
Barker DF, Cleverly J, Fain PR (1992) Two CA-dinucleotide polymorphisms at the COL4A5 (Alport syndrome) gene in Xq22. Nucleic Acids Res 20:929
Black GCM, Chen ZY, Craig IW, Powell JF (1991) Dinucleotide repeat polymorphism at the MAOA locus. Nucleic Acids Res 19:689
Browne DL, Luty JA, Litt M (1991a) Dinucleotide repeat polymorphism at the DXS538 locus. Nucleic Acids Res 19:1161
Browne DL, Zonana J, Litt M (1991b) Dinucleotide repeat polymorphism at the DXYS1X locus. Nucleic Acids Res 19:1721
Browne D, Barker D, Litt M (1992a) Dinucleotide repeat polymorphisms at the DXS365, DXS443 and DXS451 loci. Hum Mol Genet 1:213
Browne DL, Zonana J, Litt M (1992b) Dinucleotide repeat polymorphism at the PGK1P1 locus. Nucleic Acids Res 20:1169
Chatkupt S, Lucek PR, Koenigsberger MR, Johnson WG (1992) Parental sex effect in spina bifida: a role for genomic imprinting? Am J Med Genet 44:508–512
Cremers FPM, Sankila EM, Brunsman F, Jay M, Jay B, Wright A, Pinckers AJLG, Schwartz M, Pol DJR van de, Wieringa B, Chapelle A de la, Pawlowitzki IH, Ropers HH (1990) Deletions in patients with classical choroideremia vary in size from 45kb to several megabases. Am J Hum Genet 47:622–628
Donnely A, Kozman H, Gedeon A, Webb S, Lynch M, Richards R, Mulley J (1993) A genetic map of microsatellite markers on the X chromosome (abstract). 6th International Workshop on the Fragile X and X-linked Mental Retardation, p 10
Edwards JH (1987) Exclusion mapping. J Med Genet 24:539–543
Feener CA, Boyce FM, Kunkel LM (1991) Rapid detection of CA polymorphisms in cloned DNA: application to the 5′ region of the dystrophin gene. Am J Hum Genet 48:621–627
Fellous M, Boué J, Malbrunot C, Wollman E, Sasportes M, Van Cong N, Marcelli A, Rebourcet R, Hubert C, Demenais F, Elston RC, Namboodiri KK, Kaplan EB, Fellous M (1982) A five-generation family with sacral agenesis and spina bifida:possible similarities with the mouse T-locus. Am J Med Genet 12:465–487
Fineman RM, Jorde LB, Martin RA, Hasstedt SJ, Wing SD, Walker ML (1982) Spinal dysraphia as an autosomal dominant defect in four families. Am J Med Genet 12:457–464
Garber ED (1952) “Bent-tail”, a dominant sex-linked mutation in the mouse. Proc Natl Acad Sci USA 38:876–879
Hearne CM, Todd JA (1991) Tetranucleotide repeat polymorphism at the HPRT locus. Nucleic Acids Res 19:5450
Huang THM, Cottingham RW, Ledbetter DH, Zoghbi HY (1992) Genetic mapping of four dinucleotide repeat loci, DXS453, DXS458, DXS454, and DXS424, on the X-chromosome using multiplex polymerase chain reaction. Genomics 13:375–380
Jensson O, Arnason A, Gunnarsdottir H, Petursdottir I, Fossdal R, Hreidarsson S (1988) A family showing apparent X-linked inheritance of both anencephaly and spina bifida. J Med Genet 25:227–229
Kidd KK, Bowcock AM, Schmidtke J, Track R, Riccuiti F, Hutchings G, Bale A, Pearson P, Willard HF (1989) Report of the committee and catalogs of cloned and mapped genes and DNA polymorphisms. Cytogenet Cell Genet 51:622–947
Konradi C, Ozelius L, Breakefield XO (1992) Highly polymorphic (GT)n repeat sequence in intron II of the human MAOB gene. Genomics 12:176–177
Kunkel LM, Monaco AP, Middlesworth W, Ochs HD, Latt SA (1985) Specific cloning of DNA fragments absent from the DNA of a patient with an X-chromosome deletion. Proc Natl Acad Sci USA 82:4778–4782
Lafrenière RG, Brown CJ, Powers VE, Carrel L, Davies KE, Barker DF, Willard HF (1991) Physical mapping of 60 DNA markers in the p21.1→q21.3 region of the human X chromosome. Genomics 11:352–363
Lalloz MRA, McVey JH, Pattinson JK, Tuddenham EGD (1991) Haemophilia A diagnosis by analysis of a hypervariable dinucleotide repeat within the factor VIII gene. Lancet 338:207–211
Lathrop GM, Lalouel JM, Julier C, Ott J (1985) Multilocus linkage analysis in humans; detection of linkage and estimation of recombination. Am J Hum Genet 37:482–498
Luty JA, Guo Z, Willard HF, Ledbetter DH, Ledbetter S, Litt M (1990) Five polymorphic microsatellite VNTRs on the human X chromosome. Am J Hum Genet 46:776–783
Lyon MF, Kirby MC (1992) Mouse chromosome atlas. Mouse Genome 90:22–44
Mariman ECM, Hamel BCJ (1992) Sex ratios of affected and transmitting members of multiple case families with neural tube defects. J Med Genet 29:695–698
Murray JC, Ludwigsen SJ, Buetow KH (1992) A comprehensive genetic linkage map of the human genome (X chromosome). Science 258:67–86
Oman-Ganes L, Shokeir M (1984) Neural tube defects: possible X-linked recessive inheritance. Am J Hum Genet 36:67(S)
Plaja A, Vendrell T, Sarret E, Torrán N, Mediano C (1993) Terminal deletion of Xp and anencephaly (abstract 327). 25th Annual Meeting of the European Society of Human Genetics, Barcelona, Spain
Richards RI, Holman K, Kozman H, Kremer E, Lynch M, Pritchard M, Yu S, Mulley J, Sutherland GR (1991) Fragile X syndrome: genetic localisation by linkage mapping of two microsatellite repeats FRAXAC1 and FRAXAC2 which immediately flank the fragile site. J Med Genet 28:818–823
Schlessinger D, Mandel J-L, Monaco AP, Nelson DL, Willard HF (1993) Report of the Fourth International Workshop on human X chromosome mapping 1993. Cytogenet Cell Genet (in press)
Stanier P, Newton R, Forbes SA, Ivens A, Moore GE (1991) Polymorphic dinucleotide repeat at the DXS3 locus. Nucleic Acids Res 19:4793
Thompson EA (1987) Crossover counts and likelihood in multipoint linkage analysis. IMA J Math Appl Med Biol 4:93–108
Toriello H (1984) Report of a third kindred with X-linked anencephaly/spina bifida. Am J Med Genet 19:411–412
Toriello H, Warren S, Lindstrom J (1980) Possible X-linked anencephaly and spina bifida — report of a kindred. Am J Med Genet 6:119–121
Weber JL, May PE (1989) Abundant class of human DNA polymorphisms which can be typed using the polymerase chain reaction. Am J Hum Genet 44:388–396
Weber JL, Kwitek AE, May PE, Polymeropoulos MH, Ledbetter S (1990) Dinucleotide repeat polymorphisms at the DXS354, DXS454 and DXS458 loci. Nucleic Acids Res 18:4037
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Hol, F.A., Geurds, M.P.A., Jensson, O. et al. Exclusion mapping of the gene for X-linked neural tube defects in an Icelandic family. Hum Genet 93, 452–456 (1994). https://doi.org/10.1007/BF00201674
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DOI: https://doi.org/10.1007/BF00201674