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J Med Genet. Feb 2004; 41(2): 113–119.
PMCID: PMC1735660

Comparative genomic hybridisation using a proximal 17p BAC/PAC array detects rearrangements responsible for four genomic disorders

Abstract

Background: Proximal chromosome 17p is a region rich in low copy repeats (LCRs) and prone to chromosomal rearrangements. Four genomic disorders map within the interval 17p11–p12: Charcot–Marie–Tooth disease type 1A, hereditary neuropathy with liability to pressure palsies, Smith–Magenis syndrome, and dup(17)(p11.2p11.2) syndrome. While 80–90% or more of the rearrangements resulting in each disorder are recurrent, several non-recurrent deletions or duplications of varying sizes within proximal 17p also have been characterised using fluorescence in situ hybridisation (FISH).

Methods: A BAC/PAC array based comparative genomic hybridisation (array-CGH) method was tested for its ability to detect these genomic dosage differences and map breakpoints in 25 patients with recurrent and non-recurrent rearrangements.

Results: Array-CGH detected the dosage imbalances resulting from either deletion or duplication in all the samples examined. The array-CGH approach, in combination with a dependent statistical inference method, mapped 45/46 (97.8%) of the analysed breakpoints to within one overlapping BAC/PAC clone, compared with determinations done independently by FISH. Several clones within the array that contained large LCRs did not have an adverse effect on the interpretation of the array-CGH data.

Conclusions: Array-CGH is an accurate and sensitive method for detecting genomic dosage differences and identifying rearrangement breakpoints, even in LCR-rich regions of the genome.

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Selected References

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  • Bentz M, Plesch A, Stilgenbauer S, Döhner H, Lichter P. Minimal sizes of deletions detected by comparative genomic hybridization. Genes Chromosomes Cancer. 1998 Feb;21(2):172–175. [PubMed]
  • Kirchhoff M, Gerdes T, Maahr J, Rose H, Bentz M, Döhner H, Lundsteen C. Deletions below 10 megabasepairs are detected in comparative genomic hybridization by standard reference intervals. Genes Chromosomes Cancer. 1999 Aug;25(4):410–413. [PubMed]
  • Bruder CE, Hirvelä C, Tapia-Paez I, Fransson I, Segraves R, Hamilton G, Zhang XX, Evans DG, Wallace AJ, Baser ME, et al. High resolution deletion analysis of constitutional DNA from neurofibromatosis type 2 (NF2) patients using microarray-CGH. Hum Mol Genet. 2001 Feb 1;10(3):271–282. [PubMed]
  • Yu Wei, Ballif Blake C, Kashork Catherine D, Heilstedt Heidi A, Howard Leslie A, Cai Wei-Wen, White Lisa D, Liu Wenbin, Beaudet Arthur L, Bejjani Bassem A, et al. Development of a comparative genomic hybridization microarray and demonstration of its utility with 25 well-characterized 1p36 deletions. Hum Mol Genet. 2003 Sep 1;12(17):2145–2152. [PubMed]
  • Inoue K, Dewar K, Katsanis N, Reiter LT, Lander ES, Devon KL, Wyman DW, Lupski JR, Birren B. The 1.4-Mb CMT1A duplication/HNPP deletion genomic region reveals unique genome architectural features and provides insights into the recent evolution of new genes. Genome Res. 2001 Jun;11(6):1018–1033. [PMC free article] [PubMed]
  • Bi Weimin, Yan Jiong, Stankiewicz Pawe, Park Sung-Sup, Walz Katherina, Boerkoel Cornelius F, Potocki Lorraine, Shaffer Lisa G, Devriendt Koen, Nowaczyk Magorzata J M, et al. Genes in a refined Smith-Magenis syndrome critical deletion interval on chromosome 17p11.2 and the syntenic region of the mouse. Genome Res. 2002 May;12(5):713–728. [PMC free article] [PubMed]
  • Chen KS, Manian P, Koeuth T, Potocki L, Zhao Q, Chinault AC, Lee CC, Lupski JR. Homologous recombination of a flanking repeat gene cluster is a mechanism for a common contiguous gene deletion syndrome. Nat Genet. 1997 Oct;17(2):154–163. [PubMed]
  • Stankiewicz Paweł, Shaw Christine J, Dapper Jason D, Wakui Keiko, Shaffer Lisa G, Withers Marjorie, Elizondo Leah, Park Sung-Sup, Lupski James R. Genome architecture catalyzes nonrecurrent chromosomal rearrangements. Am J Hum Genet. 2003 May;72(5):1101–1116. [PMC free article] [PubMed]
  • Lupski JR, de Oca-Luna RM, Slaugenhaupt S, Pentao L, Guzzetta V, Trask BJ, Saucedo-Cardenas O, Barker DF, Killian JM, Garcia CA, et al. DNA duplication associated with Charcot-Marie-Tooth disease type 1A. Cell. 1991 Jul 26;66(2):219–232. [PubMed]
  • Pentao L, Wise CA, Chinault AC, Patel PI, Lupski JR. Charcot-Marie-Tooth type 1A duplication appears to arise from recombination at repeat sequences flanking the 1.5 Mb monomer unit. Nat Genet. 1992 Dec;2(4):292–300. [PubMed]
  • Chance PF, Alderson MK, Leppig KA, Lensch MW, Matsunami N, Smith B, Swanson PD, Odelberg SJ, Disteche CM, Bird TD. DNA deletion associated with hereditary neuropathy with liability to pressure palsies. Cell. 1993 Jan 15;72(1):143–151. [PubMed]
  • Chance PF, Abbas N, Lensch MW, Pentao L, Roa BB, Patel PI, Lupski JR. Two autosomal dominant neuropathies result from reciprocal DNA duplication/deletion of a region on chromosome 17. Hum Mol Genet. 1994 Feb;3(2):223–228. [PubMed]
  • Smith AC, McGavran L, Robinson J, Waldstein G, Macfarlane J, Zonona J, Reiss J, Lahr M, Allen L, Magenis E. Interstitial deletion of (17)(p11.2p11.2) in nine patients. Am J Med Genet. 1986 Jul;24(3):393–414. [PubMed]
  • Stratton RF, Dobyns WB, Greenberg F, DeSana JB, Moore C, Fidone G, Runge GH, Feldman P, Sekhon GS, Pauli RM, et al. Interstitial deletion of (17)(p11.2p11.2): report of six additional patients with a new chromosome deletion syndrome. Am J Med Genet. 1986 Jul;24(3):421–432. [PubMed]
  • Greenberg F, Guzzetta V, Montes de Oca-Luna R, Magenis RE, Smith AC, Richter SF, Kondo I, Dobyns WB, Patel PI, Lupski JR. Molecular analysis of the Smith-Magenis syndrome: a possible contiguous-gene syndrome associated with del(17)(p11.2). Am J Hum Genet. 1991 Dec;49(6):1207–1218. [PMC free article] [PubMed]
  • Potocki L, Chen KS, Park SS, Osterholm DE, Withers MA, Kimonis V, Summers AM, Meschino WS, Anyane-Yeboa K, Kashork CD, et al. Molecular mechanism for duplication 17p11.2- the homologous recombination reciprocal of the Smith-Magenis microdeletion. Nat Genet. 2000 Jan;24(1):84–87. [PubMed]
  • Guzzetta V, Franco B, Trask BJ, Zhang H, Saucedo-Cardenas O, Montes de Oca-Luna R, Greenberg F, Chinault AC, Lupski JR, Patel PI. Somatic cell hybrids, sequence-tagged sites, simple repeat polymorphisms, and yeast artificial chromosomes for physical and genetic mapping of proximal 17p. Genomics. 1992 Jul;13(3):551–559. [PubMed]
  • Juyal RC, Figuera LE, Hauge X, Elsea SH, Lupski JR, Greenberg F, Baldini A, Patel PI. Molecular analyses of 17p11.2 deletions in 62 Smith-Magenis syndrome patients. Am J Hum Genet. 1996 May;58(5):998–1007. [PMC free article] [PubMed]
  • Park Sung-Sup, Stankiewicz Paweł, Bi Weimin, Shaw Christine, Lehoczky Jessica, Dewar Ken, Birren Bruce, Lupski James R. Structure and evolution of the Smith-Magenis syndrome repeat gene clusters, SMS-REPs. Genome Res. 2002 May;12(5):729–738. [PMC free article] [PubMed]
  • Elsea SH, Purandare SM, Adell RA, Juyal RC, Davis JG, Finucane B, Magenis RE, Patel PI. Definition of the critical interval for Smith-Magenis syndrome. Cytogenet Cell Genet. 1997;79(3-4):276–281. [PubMed]
  • Potocki L, Chen KS, Koeuth T, Killian J, Iannaccone ST, Shapira SK, Kashork CD, Spikes AS, Shaffer LG, Lupski JR. DNA rearrangements on both homologues of chromosome 17 in a mildly delayed individual with a family history of autosomal dominant carpal tunnel syndrome. Am J Hum Genet. 1999 Feb;64(2):471–478. [PMC free article] [PubMed]
  • Shaffer LG, Kennedy GM, Spikes AS, Lupski JR. Diagnosis of CMT1A duplications and HNPP deletions by interphase FISH: implications for testing in the cytogenetics laboratory. Am J Med Genet. 1997 Mar 31;69(3):325–331. [PubMed]
  • Van Driessche Nancy, Shaw Chad, Katoh Mariko, Morio Takahiro, Sucgang Richard, Ibarra Miroslava, Kuwayama Hidekazu, Saito Tamao, Urushihara Hideko, Maeda Mineko, et al. A transcriptional profile of multicellular development in Dictyostelium discoideum. Development. 2002 Apr;129(7):1543–1552. [PubMed]
  • Wise CA, Garcia CA, Davis SN, Heju Z, Pentao L, Patel PI, Lupski JR. Molecular analyses of unrelated Charcot-Marie-Tooth (CMT) disease patients suggest a high frequency of the CMTIA duplication. Am J Hum Genet. 1993 Oct;53(4):853–863. [PMC free article] [PubMed]
  • Stankiewicz Paweł, Lupski James R. Genome architecture, rearrangements and genomic disorders. Trends Genet. 2002 Feb;18(2):74–82. [PubMed]

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