ABCMdb

PMID: 8844213

Morral N, Dork T, Llevadot R, Dziadek V, Mercier B, Ferec C, Costes B, Girodon E, Zielenski J, Tsui LC, Tummler B, Estivill X
Haplotype analysis of 94 cystic fibrosis mutations with seven polymorphic CFTR DNA markers.
Hum Mutat. 1996;8(2):149-59., [PubMed]

Sentences

No. Mutations Sentence Comment

9 ABCC7 p.Gly551Asp ABCC7 p.Trp1282* ABCC7 p.Asn1303Lys ABCC7 p.Gly542* Only four other mutations, G542X, G551D, N1303K, and W1282X, are rel- ativelyfrequent in the world Caucasoid population, and each has an overall frequency of 1-2.5% (CFGAC, 1994).Another 19mutations are found in 0.1-0.7% of chromosomes, but their distribution is variable, and in many cases they are only present in some populations (CFGAC, 1994). Login to comment 34 ABCC7 p.Asn1303Lys ABCC7 p.Gly542* The high number of haplotypes associated with mutations AF508, G542X, and N1303K suggests that they are the most ancient CF mutations in the population. Login to comment 85 ABCC7 p.Arg553* ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Arg1162* ABCC7 p.Gln552* ABCC7 p.Leu1077Pro Other haplotypes that were less commonon normal chromosomes(16-44-13, 16-35-13, 16-33-13, and 16-29-13)were each associatedwith only one CF mutation. Several mutations were associated with more than one haplotype apparentlyas the result of slippage at one of the microsatellites IVS8CA, IVS17BTA, and IVS17BCA: AF508, G542X, N1303K, R553X, Q552X, 2869insG, L1077P, 7H, and R1162X (Table 3). Login to comment 90 ABCC7 p.Arg334Trp ABCC7 p.Asn1303Lys ABCC7 p.Gly542* Mutations AF508, G542X, and N1303K were associated with severalmicrosatellite haplotypes as the result of slippage at one of the three microsat- Y R334W, 1811+1.6kbA+G, 711+IG-T, R34- ellites, giving additional support to an ancient origin of these mutations (Morral et al., 1993a, 1994a). Login to comment 91 ABCC7 p.Arg117His ABCC7 p.Arg347Pro ABCC7 p.Arg347His ABCC7 p.Arg1162* ABCC7 p.His199Tyr ABCC7 p.Leu558Ser Other mutations appeared in varioushaplotypes that were different at both microsatelliteand diallelic markers: R117H, H199Y, R347H, R347P, L558S, 2184insA, 3272-26A+G, R1162X, and 3849+10kbC-T (Table 4). Login to comment 96 ABCC7 p.Arg347Pro One example is mutation R347P, which was found associatedwith two haplotypes, only differing at microsatellites IVS8CA and IVS17BTA (Table 4); as one haplotype was associatedwith haplotype A (XV-Zc/TaqI allele 1, KM.l9/PstI allele 1) and the other with haplotype C (XV-ZdTaqIallele 2, KM.19lPstI allele l) (5` to CFTR and not shown in Table 4), an independent origin for this mutation or a double recombination can be postulated. Login to comment 97 ABCC7 p.Arg1162* Similarly, mutation R1162X has several haplotypes, three of which originated by slippage at the IVS8CA, IVS17BTA, or IVSl7BCA, but two other haplotypes with this mutation could have originated by one recombination event between exon 19 and intron 20. Login to comment 98 ABCC7 p.Arg1162* Although it is difficult to prove that these cases were due to recurrent mutations, additional R1162X chromosomesstudied in a previous report support recurrencefor this mutation (Morral et al., 1994b). Login to comment 99 ABCC7 p.Ile336Lys Mutations AF508, AI507, and I336K were found associated with haplotypes that should be the result of recombinations (Table 5). Login to comment 105 ABCC7 p.Arg117His ABCC7 p.Trp1282* ABCC7 p.Gly1244Glu ABCC7 p.Arg334Trp ABCC7 p.Arg334Trp ABCC7 p.Arg334Trp ABCC7 p.Arg347Pro ABCC7 p.Arg347Pro ABCC7 p.Arg347His ABCC7 p.Arg1162* ABCC7 p.Arg1162* ABCC7 p.Arg1162* ABCC7 p.Arg1162* ABCC7 p.Pro205Ser ABCC7 p.Gly85Glu ABCC7 p.Arg1066Cys ABCC7 p.Tyr1092* ABCC7 p.His199Tyr ABCC7 p.Lys710* ABCC7 p.His1085Arg ABCC7 p.Arg117Cys ABCC7 p.Gly91Arg ABCC7 p.Glu92Lys ABCC7 p.Trp846* ABCC7 p.Ile336Lys ABCC7 p.Glu60* ABCC7 p.Ser492Phe ABCC7 p.Gly178Arg ABCC7 p.Gly673* ABCC7 p.Cys866Tyr ABCC7 p.Val456Phe ABCC7 p.Tyr569His ABCC7 p.Leu1059* CFTR Haplotypes for Diallelic and Multiallelic DNA Markers for 94 CF Mutations" J44-GATT- 8CA-17BTA- No. of T854-TUB20 17BCA Mutation chromosomes % Normal Laboratory Reference 2-7-1-2 17-47-13 (55.4%) 17-46-13 17-45-13 17-34-13 17-32-13 17-31-14 17-31-13 17-29-14 17-28-13 16-48-13 16-46-14 16-46-13 16-45-13 16-44-13 16-35-13 16-33-13 16-32-13 16-31-14 16-31-13 16-30-13 16-29-13 16-26-13 16-25-13 16-24-13 14-31-13 1-7-2-1 17-7-17 (16.8%) R334W R334W 3860ins31 G1244E R1162X R1162X R1162X G91R MllOlK R347P R334W R117C E92K 3849+lOkbC+T 3293delA 1811+1.6kb A-tG 1811+1.6kb A-tG 2184insA P205S 3659delC G673X 11005R I336K W58S R347P W846X 405+1-A G178R 3905insT R1162X R347H 3100insA E60X 1078delT 4005+1-A K710X 1677delTA H199Y 3601-2AjG 3850-3T+G 3272-26A-tG 3850-1-A 1812-1-A R117H L1059X S492F Y1092X Y569H 3732delA C866Y 711+1G+T 711+1-T G85E 1949del84 2789+5-A H1085R W1282X R1066C 2043delG V456F 2 1 1 1 2 1 6 2 2 1 2 1 1 2 1 1 4 1 1 1 3 2 1 1 1 1 1 1 2 7 1 1 1 1 2 1 1 3 19 3 3 1 1 2 1 1 5 1 1 1 1 3 6 3 5 1 13 2 1 1 - 0.48 0.48 - - - 0.24 - - - 2.65 2.40 1.93 2.65 1.68 2.65 0.72 13.94 13.46 1.93 - 0.72 0.24 3.37 - b b fP fP fP t b,fb.fP h fb t h t h h fP fP b.h b h h b h h h h h fb fb,fP.t fP fP fP9t fP b t fPh b h fb b.fb,h fb*fP b,fP h h t h fb fb,fp,h.t fP fP fb t b.fP,t b,fb,h,t b f b h h fb b,fb.fP,h fP h h Gasparini et al. (1991b) Chilldn et al. (1993a) Devoto et al. (1991) Gasparini et al. (1991b) Dork et al. (1993a) Guillermit et al. (1993) Zielenski et al. (1993) Dean et al. (1990) Dork et al. (1994a) Nunes et al. (1993) Highsmith et al. (1994) Ghanem et al. (1994) Chilldn et al. (1995) Dork et al. (1994a) Dork et al. (1993a) Chilldn et al. (1993b) Kerem et al. (1990) Dork et al. (1994a) Dork et al. (1994a) Cuppenset al. (1993) Fanen et al. (1992) Maggio et al. (personal communication) Audrezet et al. (1993) Vidaud et al. (1990) Dork et al. (1993b) Zielenski et al. (1991a) Chilldn et al. (1994b) Malik et al. (personal communication) Cremonesi et at. Login to comment 106 ABCC7 p.Gly551Asp ABCC7 p.Arg117His ABCC7 p.Ala455Glu ABCC7 p.Arg553* ABCC7 p.Arg553* ABCC7 p.Arg553* ABCC7 p.Arg553* ABCC7 p.Arg347His ABCC7 p.Arg347His ABCC7 p.Asn1303Lys ABCC7 p.Asn1303Lys ABCC7 p.Asn1303Lys ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Gly542* ABCC7 p.Gly542* ABCC7 p.Arg1162* ABCC7 p.Val520Phe ABCC7 p.Arg560Thr ABCC7 p.Ala120Thr ABCC7 p.His199Tyr ABCC7 p.Gln39* ABCC7 p.Gln552* ABCC7 p.Gln552* ABCC7 p.Leu1077Pro ABCC7 p.Cys225Arg ABCC7 p.Ile336Lys ABCC7 p.Leu719* ABCC7 p.Arg560Lys ABCC7 p.Glu92* ABCC7 p.Phe311Leu ABCC7 p.Trp1063* ABCC7 p.Gln414* (1992) Dork et al. (1994a) Malone et al. (personal communication) Claustreset al. (1992) Ferec et al. (1992) Fanen et al. (1992) lvaschenko et al. (1991) T. Dork (personal communication) Dean et al. (1990) Dork et al. (1994a) Ferec et al. (1992) Bozon et al. (1994) Costes et al. (personal communication) Fanen et al. (1992) Audrezet et al. (personal communication) Zielenski et al. (1991a) Zielenski et al. (1991a) Granell et al. (1992) Highsmith et al. (1990) Mercier et al. (1993b) Vidaud et al. (1990) Fanen et al. (1992) Fanen et al. (1992) Dork et al. (1994b) (continued) HAPLOTYPESFOR 94 CF MUTATIONS TABLE2. CFTR HaplotvpesforDiallelic and Multiallelic DNA Markers for 94 CF Mutations"(Continued) ~~ ~ J44-GAIT- 8CA-17BTA- No. of TSU-TUB20 17BCA Mutation chromosomes % Normal Laboratory Reference 1-6-1-2 (9.1%) 1-6-2-2 (8.9%) 1-7-1-2 (3.4%) 1-7-2-2 (2.6%) 2-7-1-1 (1.2%) 2-7-2-2 (0.7%) 17-7-16 16-7-18 16-7-17 15-7-17 24-31-13 23-52-13 23-34-13 23-33-14 23-33-13 23-32-13 23-31-13 23-30-13 23-21-19 23-18-13 22-35-13 22-31-13 22-30-13 21-31-13 19-33-13 18-45-13 18-37-13 18-35-13 17-57-11 17-55-13 17-55-11 17-54-11 17-53-11 17-52-11 17-51-11 17-33-13 16-46-13 16-45-13 16-44-13 16-42-13 16-35-13 16-30-13 16-30-13 16-7-17 16-21-19 L107% L1077P 24ldelAT L719X A1507 3849+10kbC-T 2184insA 2991de132 G551D 1154insTC V520F R560T 4114ATA+lT 3667de14 435insA Q414X C225R Q39X N1303K R1162X H199Y G542X G542X w1204x R347H G542X AF50gb N1303K 2143delT 3849f 10kbC-T N1303K 681delC R347H A455E N1303K A120T 621+1 h T 574delA 1221delCT F311L R560K R553X R533X R553X Q552X R553X Q552X R116W R553X 1898+5 h T 3272-26A-G 1717-1hA 1342-2A-C A1507 2869insG 2869insG E92X 4374+1 h T 2183AA-G R117H 1609delCA I336K W1063X 1 1 1 1 6 1 3 1 1 22 17 1 1 1 1 1 1 1 1 1 1 1 1 1 17 1 1 4 157 7 1 2 2 1 1 2 2 1 9 1 1 1 1 1 1 6 1 1 1 2 1 3 2 1 3 1 1 1 4 2 4 1 1 - - 10.33 1.45 - - 0.48 1.45 - 0.24 1.45 0.24 - - - - 0.24 0.48 - - - - - - 0.49 0.48 - 0.24 0.24 0.24 - - - - - 0.72 0.24 0.72 - t h fP h b.fb,fP h b,fp.t t h b.fb.fp,h,t b.fb.fp,h,t t t t h b h h fP h fP fb b fP b.fb,fP,h.t fP fb b,fP,t b.fb,fp,h,t b.fb,h h h h,t t fb t b b b.fb.t fP fb fb tb h fP h h t t b h t h b b h h b,fb,h fP.h b h fP fP Bozon et al. (1994) Fanen et al. (1992) Dork et al. (1994a) Kerem et al. (1990) Dork et al. (1994~) Cutting et al. (1990) Kerem et al. (1990) lannuui et d. Login to comment 108 ABCC7 p.Ile148Thr ABCC7 p.Gln30* ABCC7 p.Leu558Ser (1992) (continued) TABLE2. CFTR Haplotypesfor Diallelic and MultiallelicDNA Markersfor 94 CF Mutations' (Continued) J44-GATT- 8CA-17BTA- No. of T854-TUB20 17BCA Mutation chromosomes % Normal Laboratory Reference 1-6-2-1 17-7-17 Q30X 1 - b ChillBn et al. (1994b) (0.7%) 23-7-17 I148T 1 0.48 b Bozon et al. (1994) 17-7-17 AF508 1 - fb fp1-6-1-1 20-7-17 AF508 1 fph17-7-17 AF508 2(-) 1-8-2-1 15-7-17 L558S 1 (-) 2- - -2 16- - CFBOkbdel#l 3 b Morral et al. (1993b) (-1 - - fb- "Allele1 denotesthe absence of the restriction site, whereas allele 2 denotes its presence.Numbers for microsatellites GAIT, IVSSCA, RIS17BTA. Login to comment 131 ABCC7 p.Asn1303Lys ABCC7 p.Gly542* Data based on the evolution of two other common mutations G542X and N1303K have shown that they could also be very ancient (more than 30,000 years old) (Morral et al., 1993a). Login to comment 133 ABCC7 p.Asn1303Lys ABCC7 p.Gly542* Therefore, on normal and on AF508, G542X and N1303K chromosomes, a large microsatellite haplotype variability has been generated, supporting a very ancient origin for these chromosomes. Login to comment 134 ABCC7 p.Gly85Glu Several mutations with a relative frequency of between 0.1 and 0.7% (CFGAC, 1994) are each associated with a single haplotype (1078delT, G85E, 621+lG+T), suggesting that they have a recent origin. Login to comment 135 ABCC7 p.Gly551Asp ABCC7 p.Trp1282* However, it is difficult to evaluate the age for other mutations that have relative frequencies of between 0.6 and 1.6% (G551D, 1717-1G-+A,and W1282X), but are associated with a single haplotype (17-7-17), since the numberof repeatsat IVS17BTAis very low and less susceptibleto variation. Login to comment 136 ABCC7 p.Arg553* ABCC7 p.Arg334Trp ABCC7 p.Arg347His ABCC7 p.Arg1162* ABCC7 p.Gln552* ABCC7 p.Leu1077Pro Other mutations with relative frequency of less than 0.7% are associated with more than one haplotype that should be the result of slippage at one or several microsatellite repeats (R553X, R334W, 1811+1.6kbA-+G, 711 + lG+T, Q552X, 2869insG, L1077P, R347H, and R1162X). Login to comment 138 ABCC7 p.Arg117His ABCC7 p.Arg347Pro ABCC7 p.Arg347His ABCC7 p.Arg1162* ABCC7 p.His199Tyr ABCC7 p.Leu558Ser Nine mutations (R117H, H199Y, R347H, R347P, L558S, 2184insA, 3272-26A+G, R1162X, and 3849+10kbC+T) have been found associated with more than one haplotype for both diallelic and microsatellite markers. Login to comment 141 ABCC7 p.Arg347Pro ABCC7 p.Arg347His ABCC7 p.Arg1162* In addition, fiveof them (R177H, R347H, R347P, R1162X, and 3849+1OkbC-T) have occurredat CpG dinucleotides.Although it is difficult to prove recurrence for these mutations, this has already been postulated for severalCFmu- tations (Reisset al., 1991;Kiesewetteret al., 1993; Dork et al., 1994a; Morral et al., 1994b). Login to comment