ABCMdb

PMID: 8889582

Hughes D, Wallace A, Taylor J, Tassabehji M, McMahon R, Hill A, Nevin N, Graham C
Fluorescent multiplex microsatellites used to define haplotypes associated with 75 CFTR mutations from the UK on 437 CF chromosomes.
Hum Mutat. 1996;8(3):229-35., [PubMed]

Sentences

No. Mutations Sentence Comment

6 ABCC7 p.Gly551Asp ABCC7 p.Arg117His ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Arg560Thr Ancient mutations, AF508, G542X, N1303K, were associated with several related haplotypes due to slippage during replication, whereas other common mutations were associated with the one respective haplotype (e.g., G551D and R560T with 16-7-17, R117H with 16-30-13,621+1G>T with 21-31-13,3659delC with 16-35-13). Login to comment 43 ABCC7 p.Asn1303Lys ABCC7 p.Gly542* AF508, G542X, and N1303K are ancient CFTR mutations that are the first, second, and fourth most prevalent in Northern Europe, with respective frequenciesof -70%, 2%, and 1% (CFGAC, 1994). Login to comment 50 ABCC7 p.Gly542* There are six associated haplotypes with G542X whose ancestral haplotype probably is 23-33-13, as it is found most frequentlyhere and in Spain (Morral et al., 1993). Login to comment 51 ABCC7 p.Asn1303Lys ABCC7 p.Asn1303Lys Three similar haplotypes were derived from the five N1303K chromosomes tested; 21-31-13, which was on two of the UK chromosomes,has been proposed as the ancestral N1303K haplotype (Morral et al., 1993). Login to comment 52 ABCC7 p.Arg553* Other common UK mutations were all associated with the one respective haplotype (Tables I, 2), except R553X and 1717-1G>A (see below). Login to comment 53 ABCC7 p.Gly551Asp G551D was always associated with 16-7-17 in the 26 alleles tested in the UK, four alleles tested in Spain, (Morral et al., 1993) and 19 alleles tested in the Czech Republic (Milan Macek Jr., pers. Login to comment 55 ABCC7 p.Gly551Asp This would indicate that G551D originated more recently than the three ancient mutations above but must still have spread through Europe from the original 16-7-17chromosome. Login to comment 56 ABCC7 p.Arg553* There were three haplotypes associated with R553X that differ by only three dinucleotides, where the repeat numbers are in the fifties, at the 17b TA locus. Login to comment 58 ABCC7 p.Gly551Asp ABCC7 p.Arg117His ABCC7 p.Gly85Glu ABCC7 p.Arg560Thr As the repeat number increasesbeyond 50, it probably becomes more disposed to the addition or deletion of dinucleotide repeats during replication as all other mutations where several alleles were tested gave the same respective 17bTA repeat number, i.e., G551D (17AT repeats = 7), R560T (7), G85E (24), R117H (30), 621+1G>T (31), 3659delC (354, 1898+lG>A (45). Login to comment 59 ABCC7 p.Arg553* Assuming no significant difference in the ancestry of these mutations, the increasing instability of the intron 17b TA locus as the repeat number passes 50 might be expected to give rise to several related haplotypes for R553X. Login to comment 61 ABCC7 p.Arg709* The two mutations found on haplotypes whose differences could not be explained by slippage of the DNA polymerase at one microsatelliteduring replicationwere R709X and 1717-1G>A. Login to comment 62 ABCC7 p.Arg709* The three R709X alleles typed in this study had diverse haplotypes of 1607-17,16-45-13,and 24-22-17.They were alltyped from Manchesterfamilieswith the unique 24-22-17 haplotype being of Asian origin. Login to comment 63 ABCC7 p.Arg709* R709X affects a CpGdinucleotideconsideredtobe a mutation hotspot. Login to comment 74 ABCC7 p.Gly551Asp ABCC7 p.Arg117His ABCC7 p.Arg553* ABCC7 p.Arg553* ABCC7 p.Arg553* ABCC7 p.Arg347Pro ABCC7 p.Asn1303Lys ABCC7 p.Asn1303Lys ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Gly542* ABCC7 p.Gly542* ABCC7 p.Gly542* ABCC7 p.Gly542* ABCC7 p.Arg1162* ABCC7 p.Glu831* ABCC7 p.Leu206Trp ABCC7 p.Val520Phe ABCC7 p.Gly85Glu ABCC7 p.Arg560Thr ABCC7 p.Pro67Leu ABCC7 p.Arg1158* ABCC7 p.Arg1158* ABCC7 p.Arg1283Met ABCC7 p.Val562Leu ABCC7 p.Arg117Cys ABCC7 p.Arg297Gln ABCC7 p.Tyr563Asn ABCC7 p.Arg75* ABCC7 p.Glu92Lys ABCC7 p.Ser1196* ABCC7 p.Gly1123Arg ABCC7 p.Trp1098Arg ABCC7 p.Gly178Arg ABCC7 p.Arg709* ABCC7 p.Arg709* ABCC7 p.Arg709* ABCC7 p.Leu88Ser ABCC7 p.Arg785* ABCC7 p.Leu1254* ABCC7 p.Tyr1182* ABCC7 p.Tyr917Cys CF 8CA-17bTA-17bCA Mutation chromosomes % Normal Laboratoryb Reference' HaplotVpe 1)15-29-13 557delT Nl Graham et al.. 1992 21 16-07-17 MU (G>T) 3) 16-24-13 4) 16-25-13 5) 16-29-13 6) 16-30-13 7) 16-30-14 8) 16-31-13 9) 16-31-14 10) 16-32-13 12) 16-33-13 13) 16-34-13 14) 16-35-13 11)16-32-17 15)1645-13 16) 1646-13 17) 1646-14 19) 17-07-17 18)16-53-13 20)17-29-14 21) 17-31-13 22) 17-32-13 23) 17-35-13 24) 17-51-11 25) 17-55-13 27) 17-58-13 28) 21-31-13 29) 22-31-13 31)23-22-17 26) 17-56-13 30) 22-33-13 32) 23-29-13 33)23-31-13 34)23-32-13 35)23-33-13 36)23-34-13 37) 23-36-13 38)24-22-17 39) 24-31-13 182delT P67L R75X L206W 1154insTC 146linsAGAT Q493x V520F 1717-1G>A G551D R560T V562L R709X S1196X L1254X R1283M G85E 2184insA 711+lG>T 3495delA 4279insA SlOR L88S R117C R117H G178R 1717-1G>A Y563N W1098R G1123R 3850- 1G>A E6OX %%deIT 1138insG R34P 2183AA>G 2184delA R1158X 1078delT R1162X 3849G>A Q141W R347P Y917C G2iX 711+3A>G 441delA 3130de115 3659delC 1898+1G>A R709X 2711delT R1158X E92K 3849+lOkbC>T 2118delAACT 4048insCC 296+1 2 T S Q22OX R297Q A1507 2789+5G>A 3120+1G>A W128W 1811+lG>C AF508 E831X R116W AF508 W846X1 3120G>A R785X R553X R553X R553X 621+1G>T G542X G542X Y1182X N1303K AF508 G54W 3041delG 1525-1G>A N1303K G542X G542X G542X 394delTT R709X N1303K 1 1 1 2 1 1 4 2 3 4 2 26 8 1 1 1 1 1 8 1 1 1 1 1 1 1 19 1 2 1 1 1 1 7 1 1 2 1 1 2 1 1 1 1 1 1 1 1 2 1 1 7 4 1 2 1 1 2 1 1 4 Asian 1 2 1Asian 5 4 i Afro-Caribbean 5 1 42 (19%) 1 1 57 (26%) 1 2 1 1 1 2 12 2 11.4 0.4 4.9 16.3 1.1 3.8 1.9 10.6 2.3 1.5 2.3 1.5 2.7 4.5 0.4 0.8 0.8 0.4 0.8 0.4 1 2 1 7 1 1 1Asian 1 1.5 0.8 0.8 NI G NI, M M NI NI. Login to comment 82 ABCC7 p.Gly551Asp ABCC7 p.Asn1303Lys ABCC7 p.Gly542* MicrosatelliteHaplotypesfor 16 Most Common CFTR Mutations in UK Population Mutation frequency(%)b Haplotype chromosomes Normal Laboratory" AF508 75 23-31-13 81 0.4 NI,M, G, C 17-32-13 57 0.8 NI,M, G, C 17-31-13 42 0.8 N1,M, G, C G551D 3 16-07-17 26 11.4 NI,M, G, C G542X 2 23-33-13 7 1.5 NI,C ApproximateUK 8CA-17bTA-17bCA No.CF % 22-31-13 1 NI 22-33-13 1 G 23-31-13 1 G 23-32-13 1 N1 23-34-13 1 0.8 C 621+1G>T 1 21-31-13 12 NI N1303K 0.5 23-29-13 2 NI. Login to comment 83 ABCC7 p.Arg117His ABCC7 p.Arg553* ABCC7 p.Gly85Glu ABCC7 p.Arg560Thr ABCC7 p.Glu60* G 23-31-13 2 NI,G 24-31-13 1 C R117H 16-30-13 19 16.3 NI.G, C 1717-1G>A 16-07-17 2 M, G 16-30-13 2 M, G R553X 17-55-13 1 M 17-56-13 1 C 17-58-13 1 0.4 NI 1898+1G>A 16-45-13 4 1.5 M E60X 0.2-0.5 16-31-13 7 3.8 NI.M G85E 16-24-13 8 M. G, C 1154insTC 16-07-17 4 NI, M, G A1507 17-07-17 5 4.5 NI R560T 16-07-17 8 N1 3659delC 16-35-13 7 2.3 NI. Login to comment 84 ABCC7 p.Trp1282* M, G W1282X 17-07-17 5 NI. Login to comment 91 ABCC7 p.Gly551Asp ABCC7 p.Arg117His ABCC7 p.Arg560Thr Other relativelycommon mutations (e.g., G551D, R560T, R117H, 3659delC, and 621+lG>T) were found associatedwith the one haplotype, suggesting that they emerged more recently. Login to comment 97 ABCC7 p.Gly551Asp ABCC7 p.Arg560Thr Another, 16-7-17, is highly sensitive, e.g., all G551D and R560T alleles tested were found on this framework, but has a low specificity as it is common in normals and is associated with 17 different mutations. Login to comment