ABCMdb

PMID: 7691712

Sereth H, Shoshani T, Bashan N, Kerem BS
Extended haplotype analysis of cystic fibrosis mutations and its implications for the selective advantage hypothesis.
Hum Genet. 1993 Oct 1;92(3):289-95., [PubMed]

Sentences

No. Mutations Sentence Comment

43 ABCC7 p.Asn1303Lys ABCC7 p.Gly542* The G542X, $5491, 549R and 1717- IG--+A, and N1303K mutations, were detected by PCR and subsequent allele-specific oligonucleotide (ASO) hybridization as previously described (Kerem et al. 1990; Osborne et al. 1991). Login to comment 44 ABCC7 p.Thr360Lys ABCC7 p.Gln359Lys The Q359K/T360K mutation was detected by digestion with the Rsal and Na/IIl restriction endonucleases (Shoshani et al. 1992b). Login to comment 51 ABCC7 p.Trp1282* ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Thr360Lys ABCC7 p.Thr360Lys ABCC7 p.Gln359Lys ABCC7 p.Gln359Lys Distribution of CF and normal chromosomes associated with the extended extra- and intragenic DNA polymorphic markers a 291 Mutation Haplotype 2.3A GATT TUB 18 JG2E1 24M Ethnic origin Ash- Non- Arab kena- Ash- zim kenazim AF508 Total: B 2 1 2 12 19 12 B 1 1 2 1 B (2) 1 2 4 B (2) (1) 2 1 B 2 (1) (2) 2 B 2 (1) 2 1 (B) 2 (1) 2 1 D 2 1 2 1 22 19 13 W1282X Total: B 1 2 1 40 B (1) 2 1 5 B 1 (2) 1 1 B 1 (2) (1) 3 B (1) (2) (1) 3 B 2 2 1 1 53 1 2 Q359K/T360K b Total: B 2 1 2 5 B (2) 1 2 1 B 1 1 2 1 7 N1303K Total: B 2 1 2 2 B 2 1 (2) 2 (B) (2) (1) (2) 1 3 2 G542X B 2 1 2 6 1 2 $549R B 2 1 2 2 1717-1G---)A B 1 2 1 1 $549I A 2 1 2 2 3849+10kb C--*T C 1 1 2 4 1 (C) 1 1 2 1 C 2 1 2 1 Total: 6 1 Unknown B 2 1 2 1 3 2 B (2) 1 2 1 B (2) (1) (2) 1 B 1 1 2 3 A 1 1 2 1 5 1 (A) (1) 1 2 1 C 1 1 2 2 8 2 (C) 1 (1) (2) 1 C 2 1 2 2 2 D 1 2 1 1 D 2 1 2 3 Total: 5 21 14 Total CF: 95 50 38 Table 2 (continued) Mutation Haplotype Ethnic origin 2.3A GATT TUBI8 24M Ash- Non- Arab JG2EI kena- Ash- zim kenazim Normal Total: B 2 1 2 2 1 1 B 1 l 2 3 1 B l 2 1 1 A 2 1 2 7 2 2 A I 1 2 12 8 6 A 2 2 l 1 A 1 2 2 1 A 1 2 1 I C 2 1 2 3 1 C 1 1 2 20 13 1I C 2 1 I 1 C 2 2 2 1 C 1 2 1 3 2 D 2 I 2 1 1 D 1 1 2 2 1 D 2 1 I I D 2 2 1 1 D 1 2 1 2 5 2 57 37 26 Alleles that could not be phased are shown in parentheses b All the chromosomes carrying the Q359K/T360K mutation are of Georgian origin in the respective flanking introns of the CF gene (Kerem et al. 1990; Zielenski et al. 1991). Login to comment 67 ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Thr360Lys ABCC7 p.Gln359Lys Eight additional mutations: WI282X, G542X, N1303K, 3849+10kb C---)T, Q359K/T360K, $549I, $549R, and 1717-1G-->A were identified among the studied chromosomes and have all been described elsewhere (Vidaud et al. 1990; Kerem et al. 1990; Osborne et al. 1991; Tsui 1992; Shoshani et al. 1992a, b). Login to comment 75 ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Thr360Lys ABCC7 p.Gln359Lys This extended haplotype analysis revealed that 75 of 77 (97%) of the chromosomes carrying five of the seven mutations associated with haplotype B, (F508, G542X, N1303K, Q359K/T360K, $549R) share the same intragenic haplotype, 212. Login to comment 77 ABCC7 p.Trp1282* Two mutations associated with the B haplotype, W1282X and 1717-1G--->A, were found to be associated with a completely different intragenic haplotype, 121, in 56 of 57 (98%) of the chromosomes carrying these mutations. Login to comment 78 ABCC7 p.Trp1282* One chromosome, carrying the W1282X mutation, was associated with the haplotype 221, which varies from the rest of the chromosomes at the GATT repeat site. Login to comment 84 ABCC7 p.Trp1282* ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Thr360Lys ABCC7 p.Gln359Lys The studied chromosomes included all the chromosomes carrying the Q359K/T360K, G542X, $549R, N1303K, and 1717-1G---~A mutations, 12 chromosomes carrying the W1282X mutations, and 14 chromosomes carrying the AF508 mutation. Login to comment 86 ABCC7 p.Trp1282* All chromosomes carrying the W1282X and the 1717-1G--~A mutations and associated with the intragenic haplotype 121 were associated with allele 2 at the exon 14a polymorphic site and all the rest of the studied chromosomes, associated with the intragenic haplotype 212, were associated with allele 1 at this polymorphic site. Login to comment 87 ABCC7 p.Trp1282* ABCC7 p.Thr360Lys ABCC7 p.Gln359Lys The three chromosomes (one with the W1282X mutation, one with the Q359K/T360K mutation, and one with the AF508 mutation) associated with a different allele at the repeat site were identical at the 14a polymorphic site to the rest of the chromosomes carrying the same mutation. Login to comment 88 ABCC7 p.Trp1282* Note that the number of haplotyped chromosomes carrying the W1282X mutation does not represent the frequency of this mutation in the Israeli CF population (Shoshani et al. 1992a). Login to comment 89 ABCC7 p.Trp1282* Since the W1282X mutation is associated with a rare intragenic haplotype, 121, in cases of unavailable or noninformative parents, patients heterozygous for this mutation were frequently heterozygous for the intragenic haplotype, and, therefore, their haplotype could not be phased. Login to comment 95 ABCC7 p.Trp1282* The chromosomes associated with the extended haplotype B121 carry two mutations, W1282X and 1717-1G-+A. Login to comment 96 ABCC7 p.Trp1282* The W1282X mutation accounts for 60% of CF chromosomes of Ashkenazi origin (Shoshani et al. 1992a). Login to comment 100 ABCC7 p.Trp1282* The association of a completely different intragenic haplotype with the W1282X and the 1717-1G--+A mutations indicates that the common region is not part of most of the CFTR locus itself. Login to comment 111 ABCC7 p.Trp1282* ABCC7 p.Asn1303Lys ABCC7 p.Gly542* The F508, W1282X, G542X, N1303K, and 1717-1G--+A mutations were found to be associated with the same intragenic haplotype in both ethnic groups suggesting that chromosomes carrying these mutations derive from a common origin. Login to comment 121 ABCC7 p.Trp1282* ABCC7 p.Gly542* In a previous study (Shoshani et al. 1992) we have shown that the identification of 92% of CF chromosomes of Ashkenazi origin is possible by detection of only 5 mutations (W1282X, F508, G542X, NI303K, and 1717-1G--~A). Login to comment