Genomic Rearrangements in the CFTR Gene: Extensive Allelic Heterogeneity and Diverse Mutational Mechanisms

Human Mutation

Volumn 23, Issue 4, 2004, Pages 343-357

  Audrézet, Marie Pierre ^a   Chen, Jian Min ^b   Raguenes ^a   Chuzhanova, Nadia ^c   Giteau, Karine ^a   Le Maréchal, Cédric ^b   Quéré, Isabelle ^a   Cooper, David N ^c   Férec, Claude ^a,b  

^a BREST UNIVERSITY HOSPITAL   (France)

^b UNIVERSITÉ DE BRETAGNE OCCIDENTALE   (France)

^c CARDIFF UNIVERSITY   (United Kingdom)

Author keywords

ABCC7; CF; CFTR; Cystic fibrosis; DNA repair; Gene rearrangement; L1; LINE 1; Mutational mechanisms; Nonhomologous recombination; QMPSF; Retrotransposon

Indexed keywords

TRANSMEMBRANE CONDUCTANCE REGULATOR;

ALLELE; ARTICLE; CFTR GENE; CLINICAL ARTICLE; COHORT ANALYSIS; CYSTIC FIBROSIS; GEL ELECTROPHORESIS; GENE; GENE DELETION; GENE MUTATION; GENE REARRANGEMENT; GENETIC HETEROGENEITY; GENETIC RECOMBINATION; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; MUTAGENESIS; NUCLEOTIDE SEQUENCE; POLYMERASE CHAIN REACTION; PRIORITY JOURNAL; SEQUENCE HOMOLOGY;

ALLELES; BASE SEQUENCE; CHROMOSOME BREAKAGE; CYSTIC FIBROSIS; CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR; GENOME, HUMAN; HUMANS; MODELS, GENETIC; MOLECULAR SEQUENCE DATA; MUTAGENESIS, INSERTIONAL; MUTATION; POLYMERASE CHAIN REACTION; RECOMBINATION, GENETIC; SEQUENCE ALIGNMENT; SEQUENCE DELETION;

INSERTION SEQUENCES;

EID: 1842665159     PISSN: 10597794     EISSN: None     Source Type: Journal    
DOI: 10.1002/humu.20009     Document Type: Article

References (75)

1. Abeysinghe SS, Chuzhanova N, Krawczak M, Ball EV, Cooper DN. 2003. Translocation and gross deletion breakpoints in human inherited disease and cancer I. Nucleotide composition and recombination-associated motifs. Hum Mutat 22: 229-244.
2. Albertini AM, Hofer M, Calos MP, Miller JH. 1982. On the formation of spontaneous deletions: the importance of short sequence homologies in the generation of large deletions. Cell 29:319-328.
3. Audrezet MP, Mercier B, Guillermit H, Quere I, Verlingue C, Rault G, Ferec C. 1993. Identification of 12 novel mutations in the CFTR gene. Hum Mol Genet 2:51-54.
4. Bobadilla JL, Macek M Jr, Fine JP, Farrell PM. 2002. Cystic fibrosis: a worldwide analysis of CFTR mutations-correlation with incidence data and application to screening. Hum Mutat 19:575-606.
5. Brouha B, Schustak J, Badge RM, Lutz-Prigge S, Farley AH, Moran JV, Kazazian HH Jr. 2003. Hot L1s account for the bulk of retrotransposition in the human population. Proc Natl Acad Sci USA 100:5280-5285.
6. Canning S, Dryja TP. 1989. Short, direct repeats at the breakpoints of deletions of the retinoblastoma gene. Proc Natl Acad Sci USA 86:5044-5048.
7. Casilli F, Di Rocco ZC, Gad S, Tournier I, Stoppa-Lyonnet D, Frebourg T, Tosi M. 2002. Rapid detection of novel BRCA1 rearrangements in high-risk breast-ovarian cancer families using multiplex PCR of short fluorescent fragments. Hum Mutat 20:218-226.
8. Charbonnier F, Raux G, Wang Q, Drouot N, Cordier F, Limacher JM, Saurin JC, Puisieux A, Olschwang S, Frebourg T. 2000. Detection of exon deletions and duplications of the mismatch repair genes in hereditary nonpolyposis colorectal cancer families using multiplex polymerase chain reaction of short fluorescent fragments. Cancer Res 60:2760-2763.
9. Charbonnier F, Olschwang S, Wang Q, Boisson C, Martin C, Buisine MP, Puisieux A, Frebourg T. 2002. MSH2 in contrast to MLH1 and MSH6 is frequently inactivated by exonic and promoter rearrangements in hereditary nonpolyposis colorectal cancer. Cancer Res 62:848-853.
10. Chen JM, Cutler C, Jacques C, Boeuf G, Denamur E, Lecointre G, Mercier B, Cramb G, Ferec C. 2001a. A combined analysis of the cystic fibrosis transmembrane conductance regulator: implications for structure and disease models. Mol Biol Evol 18:1771-1788.
11. Chen X, Kinoshita K, Honjo T. 2001b. Variable deletion and duplication at recombination junction ends: implication for staggered double-strand cleavage in class-switch recombination. Proc Natl Acad Sci USA 98:13860-13865.
12. Chevalier-Porst F, Bonardot AM, Chazalette JP, Mathieu M, Bozon D. 1998. 40 kilobase deletion (CF 40 kb del 4-10) removes exons 4 to 10 of the Cystic Fibrosis Transmembrane Conductance Regulator gene. Hum Mutat Suppl 1: S291-S294.
13. Choi JY, Muallem D, Kiselyov K, Lee MG, Thomas PJ, Muallem S. 2001. Aberrant CFTR-dependent HCO3- transport in mutations associated with cystic fibrosis. Nature 410:94-97.
14. Chuzhanova N, Abeysinghe SS, Krawczak M, Cooper DN. 2003a. Translocation and gross deletion breakpoints in human inherited disease and cancer II. Potential involvement of repetitive sequence elements in secondary structure formation between DNA ends. Hum Mutat 22:245-251.
15. Chuzhanova NA, Anassis E, Ball E, Krawczak M, Cooper DN. 2003b. Meta-analysis of indels causing human genetic disease: mechanisms of mutagenesis and the role of local DNA sequence complexity. Hum Mutat 21:28-44.
16. Costes B, Girodon E, Vidaud D, Flori E, Ardalan A, Conteville P, Fanen P, Niel F, Vidaud M, Goossens M. 2000. Prenatal detection by real-time quantitative PCR and characterization of a new CFTR deletion, 3600+15kbdel5.3kb (or CFTRdele19). Clin Chem 46:1417-1420.
17. den Dunnen JT, Antonarakis SE. 2000. Mutation nomenclature extensions and suggestions to describe complex mutations: a discussion. Hum Mutat 15:7-12.
18. Dombroski BA, Feng Q, Mathias SL, Sassaman DM, Scott AF, Kazazian HH Jr, Boeke JD. 1994. An in vivo assay for the reverse transcriptase of human retrotransposon L1 in Saccharomyces cerevisiae. Mol Cell Biol 14:4485-4492.
19. Dork T, Macek M Jr, Mekus F, Tummler B, Tzountzouris J, Casals T, Krebsova A, Koudova M, Sakmaryova I, Macek M Sr, Vavrova V, Zemkova D, Ginter E, Petrova NV, Ivaschenko T, Baranov V, Witt M, Pogorzelski A, Bal J, Zekanowsky C, Wagner K, Stuhrmann M, Bauer I, Seydewitz HH, Neumann T, Jakubiczka S, Kraus C, Thamm B, Nechiporenko M, Livshits L, Mosse N, Tsukerman G, Kadasi L, Ravnik-Glavac M, Glavac D, Komel R, Vouk K, Kucinskas V, Krumina A, Teder M, Kocheva S, Efremov GD, Onay T, Kirdar B, Malone G, Schwarz M, Zhou Z, Friedman KJ, Carles S, Claustres M, Bozon D, Verlingue C, Ferec C, Tzetis M, Kanavakis E, Cuppens H, Bombieri C, Pignatti PF, Sangiuolo F, Jordanova A, Kusic J, Radojkovic D, Sertic J, Richter D, Stavljenic Rukavina A, Bjorck E, Strandvik B, Cardoso H, Montgomery M, Nakielna B, Hughes D, Estivill X, Aznarez I, Tullis E, Tsui LC, Zielenski J. 2000. Characterization of a novel 21-kb deletion, CFTRdele2,3(21 kb), in the CFTR gene: a cystic fibrosis mutation of Slavic origin common in Central and East Europe. Hum Genet 106:259-268.
20. Duponchel C, Di Rocco C, Cicardi M, Tosi M. 2001. Rapid detection by fluorescent multiplex PCR of exon deletions and duplications in the C1 inhibitor gene of hereditary angioedema patients. Hum Mutat 17:61-70.
21. Ellsworth RE, Jamison DC, Touchman JW, Chissoe SL, Braden Maduro VV, Bouffard GG, Dietrich NL, Beckstrom-Sternberg SM, Iyer LM, Weintraub LA, Cotton M, Courtney L, Edwards J, Maupin R, Ozersky P, Rohlfing T, Wohldmann P, Miner T, Kemp K, Kramer J, Korf I, Pepin K, Antonacci-Fulton L, Fulton RS, Minx P, Hillier LW, Wilson RK, Waterston RH, Miller W, Green ED. 2000. Comparative genomic sequence analysis of the human and mouse cystic fibrosis transmembrane conductance regulator genes. Proc Natl Acad Sci USA 97: 1172-1177.
22. Farabaugh PJ, Schmeissner U, Hofer M, Miller JH. 1978. Genetic studies of the lac repressor. VII. On the molecular nature of spontaneous hotspots in the lacI gene of Escherichia coli. J Mol Biol 126:847-857.
23. Ferec C, Audrezet MP, Mercier B, Guillermit H, Moullier P, Quere I, Verlingue C. 1992. Detection of over 98% cystic fibrosis mutations in a Celtic population. Nat Genet 1: 188-191.
24. George JA, Burke WD, Eickbush TH. 1996. Analysis of the 5′ junctions of R2 insertions with the 28S gene: implications for non-LTR retrotransposition. Genetics 142:853-863.
25. Gilbert N, Lutz-Prigge S, Moran JV. 2002. Genomic deletions created upon LINE-1 retrotransposition. Cell 110:315-325.
26. Girodon-Boulandet E, Cazeneuve C, Goossens M. 2000. Screening practices for mutations in the CFTR gene ABCC7. Hum Mutat 15:135-149.
27. Goodier JL, Ostertag EM, Kazazian HH Jr. 2000. Transduction of 3′-flanking sequences is common in L1 retrotransposition. Hum Mol Genet 9:653-657.
28. Henthorn PS, Smithies O, Mager DL. 1990. Molecular analysis of deletions in the human beta-globin gene cluster: deletion junctions and locations of breakpoints. Genomics 6:226-237.
29. Jaeger U, Purtscher B, Karth GD, Knapp S, Mannhalter C, Lechner K. 1993. Mechanism of the chromosomal translocation t(14;18) in lymphoma: detection of a 45-kd breakpoint binding protein. Blood 81:1833-1840.
30. Jeffs AR, Benjes SM, Smith TL, Sowerby SJ, Morris CM. 1998. The BCR gene recombines preferentially with Alu elements in complex BCR-ABL translocations of chronic myeloid leukaemia. Hum Mol Genet 7:767-776.
31. Kerem B, Rommens JM, Buchanan JA, Markiewicz D, Cox TK, Chakravarti A, Buchwald M, Tsui LC. 1989. Identification of the cystic fibrosis gene: genetic analysis. Science 245: 1073-1080.
32. Ketterling RP, Ricke DO, Wurster MW, Sommer SS. 1993. Deletions with inversions: report of a mutation and review of the literature. Hum Mutat 2:53-57.
33. Kilinc MO, Ninis VN, Dagli E, Demirkol M, Ozkinay F, Arikan Z, Cogulu O, Huner G, Karakoc F, Tolun A. 2002. Highest heterogeneity for cystic fibrosis: 36 mutations account for 75% of all CF chromosomes in Turkish patients. Am J Med Genet 113:250-257.
34. Kimberland ML, Divoky V, Prchal J, Schwahn U, Berger W, Kazazian HH Jr. 1999. Full-length human L1 insertions retain the capacity for high frequency retrotransposition in cultured cells. Hum Mol Genet 8:1557-1560.
35. Kornreich R, Bishop DF, Desnick RJ. 1990. Alpha-galactosidase A gene rearrangements causing Fabry disease. Identification of short direct repeats at breakpoints in an Alu-rich gene. J Biol Chem 265:9319-9326.
36. Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J, Devon K, Dewar K, Doyle M, FitzHugh W, Funke R, Gage D, Harris K, Heaford A, Howland J, Kann L, Lehoczky J, LeVine R, McEwan P, McKeman K, Meldrim J, Mesirov JP, Miranda C, Morris W, Naylor J, Raymond C, Rosetti M, Santos R, Sheridan A, Sougnez C, Stange-Thomann N, Stojanovic N, Subramanian A, Wyman D, Rogers J, Sulston J, Ainscough R, Beck S, Bentley D, Burton J, Clee C, Carter N, Coulson A, Deadman R, Deloukas P, Dunham A, Dunham I, Durbin R, French L, Grafham D, Gregory S, Hubbard T, Humphray S, Hunt A, Jones M, Lloyd C, McMurray A, Matthews L, Mercer S, Milne S, Mullikin JC, Mungall A, Plumb R, Ross M, Shownkeen R, Sims S, Waterston RH, Wilson RK, Hillier LW, McPherson JD, Marra MA, Mardis ER, Fulton LA, Chinwalla AT, Pepin KH, Gish WR, Chissoe SL, Wendl MC, Delehaunty KD, Miner TL, Delehaunty A, Kramer JB, Cook LL, Fulton RS, Johnson DL, Minx PJ, Clifton SW, Hawkins T, Branscomb E, Predki P, Richardson P, Wenning S, Slezak T, Doggett N, Cheng JF, Olsen A, Lucas S, Elkin C, Uberbacher E, Frazier M, Gibbs RA, Muzny DM, Scherer SE, Bouck JB, Sodergren EJ, Worley KC, Rives CM, Gorrell JH, Metzker ML, Naylor SL, Kucherlapati RS, Nelson DL, Weinstock GM, Sakaki Y, Fujiyama A, Hattori M, Yada T, Toyoda A, Itoh T, Kawagoe C, Watanabe H, Totoki Y, Taylor T, Weissenbach J, Heilig R, Saurin W, Artiguenave F, Brottier P, Bruls T, Pelletier E, Robert C, Wincker P, Smith DR, Doucette-Stamm L, Rubenfield M, Weinstock K, Lee HM, Dubois J, Rosenthal A, Platzer M, Nyakatura G, Taudien S, Rump A, Yang H, Yu J, Wang J, Huang G, Gu J, Hood L, Rowen L, Madan A, Qin S, Davis RW, Federspiel NA, Abola AP, Proctor MJ, Myers RM, Schmutz J, Dickson M, Grimwood J, Cox DR, Olson MV, Kaul R, Raymond C, Shimizu N, Kawasaki K, Minoshima S, Evans GA, Athanasiou M, Schultz R, Roe BA, Chen F, Pan H, Ramser J, Lehrach H, Reinhardt R, McCombie WR, de la Bastide M, Dedhia N, Blocker H, Hornischer K, Nordsiek G, Agarwala R, Aravind L, Bailey JA, Bateman A, Batzoglou S, Birney E, Bork P, Brown DG, Burge CB, Cerutti L, Chen HC, Church D, Clamp M, Copley RR, Doerks T, Eddy SR, Eichler EE, Furey TS, Galagan J, Gilbert JG, Harmon C, Hayashizaki Y, Haussler D, Hermjakob H, Hokamp K, Jang W, Johnson LS, Jones TA, Kasif S, Kaspryzk A, Kennedy S, Kent WJ, Kitts P, Koonin EV, Korf I, Kulp D, Lancet D, Lowe TM, McLysaght A, Mikkelsen T, Moran JV, Mulder N, Pollara VJ, Ponting CP, Schuler G, Schultz J, Slater G, Smit AF, Stupka E, Szustakowski J, Thierry-Mieg D, Thierry-Mieg J, Wagner L, Wallis J, Wheeler R, Williams A, Wolf YI, Wolfe KH, Yang SP, Yeh RF, Collins F, Guyer MS, Peterson J, Felsenfeld A, Wetterstrand KA, Patrinos A, Morgan MJ, Szustakowki J, de Jong P, Catanese JJ, Osoegawa K, Shizuya H, Choi S, Chen YJ, International Human Genome Sequencing Consortium. 2001. Initial sequencing and analysis of the human genome. Nature 409:860-921.
37. Le Marechal C, Audrezet MP, Quere I, Raguenes O, Langonne S, Ferec C. 2001. Complete and rapid scanning of the cystic fibrosis transmembrane conductance regulator (CFTR) gene by denaturing high-performance liquid chromatography (D-HPLC): major implications for genetic counselling. Hum Genet 108:290-298.
38. Lerer I, Laufer-Cahana A, Rivlin JR, Augarten A, Abeliovich D. 1999. A large deletion mutation in the CFTR gene (3120+1Kbdel8.6Kb): a founder mutation in the Palestinian Arabs. Mutation in brief no. 231. Online. Hum Mutat 13:337.
39. Li L, Bray PF. 1993. Homologous recombination among three intragene Alu sequences causes an inversion-deletion resulting in the hereditary bleeding disorder Glanzmann thrombasthenia. Am J Hum Genet 53:140-149.
40. Lilley DM. 1988. DNA opens up-supercoiling and heavy breathing. Trends Genet 4:111-114.
41. Love DR, England SB, Speer A, Marsden RF, Bloomfield JF, Roche AL, Cross GS, Mountford RC, Smith TJ, Davies KE. 1991. Sequences of junction fragments in the deletion-prone region of the dystrophin gene. Genomics 10:57-67.
42. Luan DD, Korman MH, Jakubczak JL, Eickbush TH. 1993. Reverse transcription of R2Bm RNA is primed by a nick at the chromosomal target site: a mechanism for non-LTR retrotransposition. Cell 72:595-605.
43. Aγδβ)° thalassemia deletion: comparison to other deletions in the human β-globin gene cluster and sequence analysis of the breakpoints. Nucleic Acids Res 13:6559-6575.
44. Magnani C, Cremonesi L, Giunta A, Magnaghi P, Taramelli R, Ferrari M. 1996. Short direct repeats at the breakpoints of a novel large deletion in the CFTR gene suggest a likely slipped mispairing mechanism. Hum Genet 98:102-108.
45. Mathews DH, Sabina J, Zuker M, Turner DH. 1999. Expanded sequence dependence of thermodynamic parameters improves prediction of RNA secondary structure. J Mol Biol 288:911-940.
46. Mekus F, Ballmann M, Bronsveld I, Dork T, Bijman J, Tummler B, Veeze HJ. 1998. Cystic-fibrosis-like disease unrelated to the cystic fibrosis transmembrane conductance regulator. Hum Genet 102:582-586.
47. Mickle JE, Macek M Jr, Fulmer-Smentek SB, Egan MM, Schwiebert E, Guggino W, Moss R, Cutting GR. 1998. A mutation in the cystic fibrosis transmembrane conductance regulator gene associated with elevated sweat chloride concentrations in the absence of cystic fibrosis. Hum Mol Genet 7:729-735.
48. Moran JV, Gilbert N. 2002. Mammalian LINE-1 retrotransposons and related elements. In: Craig N, Craggie R, Gellert M, Lambowitz A, editors. Mobile DNA II. Washington, D.C.: ASM. p 836-869.
49. Morral N, Nunes V, Casals T, Cobos N, Asensio O, Dapena J, Estivill X. 1993. Uniparental inheritance of microsatellite alleles of the cystic fibrosis gene (CFTR): identification of a 50 kilobase deletion. Hum Mol Genet 2:677-681.
50. Morris T, Thacker J. 1993. Formation of large deletions by illegitimate recombination in the HPRT gene of primary human fibroblasts. Proc Natl Acad Sci USA 90:1392-1396.
51. Morrish TA, Gilbert N, Myers JS, Vincent BJ, Stamato TD, Taccioli GE, Batzer MA, Moran JV. 2002. DNA repair mediated by endonuclease-independent LINE-1 retrotransposition. Nat Genet 31:159-165.
52. Ostertag EM, Kazazian HH Jr. 2001. Biology of mammalian L1 retrotransposons. Annu Rev Genet 35:501-538.
53. Pagani F, Buratti E, Stuani C, Romano M, Zuccato E, Niksic M, Giglio L, Faraguna D, Baralle FE. 2000. Splicing factors induce cystic fibrosis transmembrane regulator exon 9 skipping through a nonevolutionary conserved intronic element. J Biol Chem 275:21041-21047.
54. Pagani F, Stuani C, Zuccato E, Kornblihtt AR, Baralle FE. 2003. Promoter architecture modulates CFTR exon 9 skipping. J Biol Chem 278:1511-1517.
55. Pickeral OK, Makalowski W, Boguski MS, Boeke JD. 2000. Frequent human genomic DNA transduction driven by LINE-1 retrotransposition. Genome Res 10:411-415.
56. Ratjen F, Doring G. 2003. Cystic fibrosis. Lancet 361:681-689.
57. Riordan JR, Rommens JM, Kerem B, Alon N, Rozmahel R, Grzelczak Z, Zielenski J, Lok S, Plavsic N, Chou JL, Drumm ML, Iannuzzi MC, Collins FS, Tsui LC. 1989. Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA. Science 245:1066-1073.
58. Roth DB, Porter TN, Wilson JH. 1985. Mechanisms of nonhomologous recombination in mammalian cells. Mol Cell Biol 5:2599-2607.
59. Rudiger NS, Gregersen N, Kielland-Brandt MC. 1995. One short well conserved region of Alu-sequences is involved in human gene rearrangements and has homology with prokaryotic chi. Nucleic Acids Res 23:256-260.
60. Schwiebert EM, Egan ME, Hwang TH, Fulmer SB, Allen SS, Cutting GR, Guggino WB. 1995. CFTR regulates outwardly rectifying chloride channels through an autocrine mechanism involving ATP. Cell 81:1063-1073.
61. Shrimpton AE, Borowitz D, Swender P. 1997. Cystic fibrosis mutation frequencies in upstate New York. Hum Mutat 10:436-442.
62. Solera J, Magallon M, Martin-Villar J, Coloma A. 1992. Factor IXMadrid 2: a deletion/insertion in factor IX gene which abolishes the sequence of the donor junction at the exon IV-intron d splice site. Am J Hum Genet 50:434-437.
63. Sommer SS, Ketterling RP. 1993. A postulated mechanism for deletions with inversions. Am J Hum Genet 52:1016-1018.
64. Strachan T, Read AP. 1999. Human molecular genetics. New York: John Wiley & Sons. p 219.
65. Streisinger G, Okada Y, Emrich J, Newton J, Tsugita A, Terzaghi E, Inouye M. 1966. Frameshift mutations and the genetic code. Cold Spring Harb Symp Quant Biol 31:77-84.
66. Symer DE, Connelly C, Szak ST, Caputo EM, Cost GJ, Parmigiani G, Boeke JD. 2002. Human L1 retrotransposition is associated with genetic instability in vivo. Cell 110:327-338.
67. Teng SC, Kim B, Gabriel A. 1996. Retrotransposon reverse-transcriptase-mediated repair of chromosomal breaks. Nature 383:641-644.
68. Van de Water N, Williams R, Ockelford P, Browett P. 1998. A 20.7 kb deletion within the factor VIII gene associated with LINE-1 element insertion. Thromb Haemost 79:938-942.
69. Vankeerberghen A, Cuppens H, Cassiman JJ. 2002. The cystic fibrosis transmembrane conductance regulator: an intriguing protein with pleiotropic functions. J Cystic Fibrosis 1:13-29.
70. Viel A, Petronzelli F, Della Puppa L, Lucci-Cordisco E, Fornasarig M, Pucciarelli S, Rovella V, Quaia M, Ponz de Leon M, Boiocchi M, Genuardi M. 2002. Different molecular mechanisms underlie genomic deletions in the MLH1 gene. Hum Mutat 20:368-374.
71. Welsh MJ, Ramsey BW, Accurso FJ, Cutting GR. 2001. Cystic fibrosis. In: Scriver CR, Beaudet AL, Sly WS, Valle D, Childs B, Vogelstein B, editors. The metabolic and molecular bases of inherited disease. New York: McGraw-Hill. p 5121-5189.
72. Williams SH, Mouchel N, Harris A. 2003. A comparative genomic analysis of the cow, pig, and human CFTR genes identifies potential intronic regulatory elements. Genomics 81:628-639.
73. Woods-Samuels P, Kazazian HH Jr, Antonarakis SE. 1991. Nonhomologous recombination in the human genome: deletions in the human factor VIII gene. Genomics 10:94-101.
74. Zielenski J, Rozmahel R, Bozon D, Kerem B, Grzelczak Z, Riordan JR, Rommens J, Tsui LC. 1991. Genomic DNA sequence of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Genomics 10:214-228.
75. Zielenski J, Tsui LC. 1995. Cystic fibrosis: genotypic and phenotypic variations. Annu Rev Genet 29:777-807.