Abstract
In order to contribute to the development of the transcriptional map of human chromosome 21 (HC21) we have used exon trapping to identify portions of HC21 genes. Using pools of random HC21-specific cosmids from the LL21NC02-Q library and cosmids from 21q22.3 we have identified five different coding regions with strong homology to the lanosterol synthase genes of rat and yeast. This enzyme catalyzes the cyclization of squalene-2,3-epoxide to lanosterol, which is the parental compound of all steroids in mammals. Using somatic cell hybrids and HC21 yeast artificial chromosomes (YACs) and cosmids, we mapped the human lanosterol synthase gene to 21q22.3 between markers D21S25 and 21qter. Cosmid Q7G8 from the LL21NC02-Q library and YAC 145D8 from the CEPH HC21 contig contain this human gene. We cloned a portion of the human lanosterol synthase cDNA (almost 85% of the coding region) from a brain cDNA library and determined its nucleotide sequence. The predicted human protein shows 83% identity to its rat and 40% to its yeast homolog. No obvious candidate human disease exists for lanosterol synthase deficiency and the role (if any) of triplication of this gene in the various phenotypes of trisomy 21 is unknown.
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Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ (1990) Basic local alignment search tool. J Mol Biol 215:403–410
Antonarakis SE (1993) Human chromosome 21: genome mapping and exploration circa 1993. Trends Genet 9:142–148
Buckler AJ, Cheng DD, Graw SL, Brook JD, Haber DA, Sharp PA, Housman DE (1991) Exon amplification: a strategy to isolate mammalian genes based on RNA splicing. Proc Natl Acad Sci USA 88:4005–4009
Chen HM, Chrast R, Rossier C, Morris MA, Lalioti MD, Antonarakis SE (1995) Cloning of portions of approximately 40% of the genes on human chromosome 21 by exon trapping. Am J Hum Genet 57:A142
Cheng JF, Boyartchuk V, Zhu YW (1994) Isolation and mapping of human chromosome 21 cDNA: progress in constructing a chromosome 21 expression map. Genomics 23:75–84
Chumakov IM, Rigault P, Guillou S, Ougen P, Billaut A, Guasconi G, Gervy P, LeGall I, Soularue P, Grinas L, Bougueleret L, Bellanne-Chantelot C, Lacroix B, Barillot E, Gesnouin P, Pook S, Vayssiex G, Frelat G, Schmitz A, Sambucy JL, Bosch A, Estivill X, Weissenbach J, Vignal A, Riethman H, Cox D, Patterson D, Gardiner K, Hattori M, Sakaki Y, Ichikawa H, Ohki M, Le Paslier D, Heilig R, Antonarakis SE, Cohen D (1992) A continuum of overlapping clones spanning the entire chromosome 21. Nature 359:380–387
Church DM, Stotler CJ, Rutter JL, Murrell JR, Trofatter JA, Buckler AJ (1994) Isolation of genes from complex sources of mammalian genomic DNA using exon amplification. Nature Genet 6:98–105
Corey EJ, Dean PDG, Ortiz de Montellando PR, Bloch K (1966) A soluble 2,3-oxidosqualene sterol cyclase. J Biol Chem 242:3014–3019
Corey EJ, Matsuda SPT, Bartel B (1994) Molecular cloning, characterization, and overexpression of ERG7, theSaccharomyces cerevisiae gene encoding lanosterol synthase. Proc Natl Acad Sci USA 91:2211–2215
Delabar JM, Theophile D, Rahmani Z, Chettouh Z, Blouin JL, Prieur M, Noel B, Sinet PM (1993) Molecular mapping of twenty-four features of Down syndrome on chromosome 21. Eur J Hum Genet 1:114–124
Gibco BRL (1994) Exon trapping system. Instruction manual 18449-017
Korenberg JR, Chen XN, Schipper R, Sun Z, Gonsky R, Gerwehr S, Carpenter N, Daumer D, Dignan P, Disteche C, Graham JM, Hugdins L, McGillivray B, Miyazaki K, Ogasawara N, Park JP, Pagon R, Pueschel S, Sack G, Say B, Schuffenhauer S, Soukup S, Yamanaka T (1994) Down syndrome phenotypes: the consequences of chromosomal inbalance. Proc Natl Acad Sci USA 91:4997–5001
Kusano M, Shibuya M, Sankawa U, Ebizuka Y (1995) Molecular cloning of cDNA encoding rat 2,3-oxidosqualene: lanosterol cyclase. Biol Pharm Bull 18:195–197
Lucente D, Chen HM, Shea D, Samec SN, Rutter M, Chrast R, Rossier C, Buckler A, Antonarakis SE, McCormick MK (1995) Localization of 102 exons to a 2.5 Mb region involved in Down syndrome. Hum Mol Genet 4:1305–1311
McCormick MK, Schinzel A, Petersen MB, Stetten G, Driscoll DJ, Cantu, ES, Tranebjaerg L, Mikkelsen M, Watkins PC, Antonarakis SE (1989) Molecular genetics approach to the characterization of the “Down syndrome region” of chromosome 21. Genomics 5:325–331
McInnis MG, Chakravarti A, Blaschak J, Petersen MB, Sharma V, Avramopoulos D, Blouin JL, Konig U, Brahe C, Cox Matise T, Warren AC, Talbot CC Jr, Van Broeckhoven C, Litt M, Antonarakis SE (1993) A linkage map of human chromosome 21: 43 markers at average interval of 2.5 cM. Genomics 16:562–571
Nizetic D, Gellen L, Hamvas RMJ, Mott R, Grigoriev A, Vatcheva R, Zehetner G, Yaspo ML, Dutriaux A, Lopes C, Delabar JM, Van Broeckhoven C, Potier MC, Lehrach H (1994) An integrated YAC-overlap and “cosmid-pocket” map of the human chromosome 21. Hum Mol Genet 3:759–770
Patterson D, Rahmani Z, Donaldson D, Gardiner K, Jones C (1993) Physical mapping of chromosome 21. Prog Clin Biol Res 384:33–50
Peterson A, Patil N, Robbins C, Wang L, Cox DR, Myers RM (1994) A transcript map of the Down syndrome critical region on chromosome 21. Hum Mol Genet 3:1735–1742
Roessner CA, Min C, Hardin SH, Harris-Haller LW, McCollum JC, Scott AI (1993) Sequence of theCandida albicans erg7 gene. Gene 127:149–150
Soeda E, Hou DX, Osoegawa Y, Atsuchi T, Yamagata T, Shimokawa H, Kishida H, Soeda E, Okano S, Chumakov I, Cohen D, Raff M, Gardiner K, Graw S, Patterson D, De Jong P, Ashworth L, Slezak T, Carrano A (1995) Cosmid assembly and anchoring to human chromosome 21. Genomics 25:73–84
Xu H, Wei H, Tassone F, Graw S, Gardiner K, Weissman S (1995) A search for genes from the dark band regions of human chromosome 21. Genomics 27:1–8
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Young, M., Chen, H., Lalioti, M.D. et al. The human lanosterol synthase gene maps to chromosome 21q22.3. Hum Genet 97, 620–624 (1996). https://doi.org/10.1007/BF02281872
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DOI: https://doi.org/10.1007/BF02281872