ABCMdb

PMID: 11713719

Mateu E, Calafell F, Ramos MD, Casals T, Bertranpetit J
Can a place of origin of the main cystic fibrosis mutations be identified?
Am J Hum Genet. 2002 Jan;70(1):257-64. Epub 2001 Nov 16., [PubMed]

Sentences

No. Mutations Sentence Comment

20 ABCC7 p.Gly551Asp ABCC7 p.Trp1282* ABCC7 p.Asn1303Lys ABCC7 p.Gly542* Only four other mutations (G542X, N1303K, G551D, and W1282X) have overall frequencies 11% among the CF chromosomes. Login to comment 22 ABCC7 p.Gly542* G542X is common in Mediterranean countries and is present in most of Europe, being most frequent (16.7%) in the Balearic Islands (Estivill et al. 1997). Login to comment 23 ABCC7 p.Asn1303Lys N1303K is present around the Mediterranean, and it reaches its highest frequency (17.2%) in Tunisia (Estivill et al. 1997). Login to comment 24 ABCC7 p.Gly551Asp Mutation G551D is common in northwestern and central Europe, but it is uncommon in other parts of Europe (Estivill et al. 1997). Login to comment 25 ABCC7 p.Trp1282* Finally, mutation W1282X is common in most Mediterranean countries, reaching its highest frequency (36.2%) in Israel (Estivill et al. 1997). Login to comment 26 ABCC7 p.Gly551Asp ABCC7 p.Trp1282* ABCC7 p.Asn1303Lys ABCC7 p.Gly542* In addition, 17 other mutations have frequencies of 0.1%-0.9% (Estiv- Figure 1 Polymorphisms in the CFTR region (IVS1CA, IVS6aGATT, IVS8CA, T854, IVS17bTA, and TUB20), and location of the five most common CF mutations (DF508, G542X, N1303K, G551D, and W1282X). Login to comment 48 ABCC7 p.Asn1303Lys ABCC7 p.Gly542* OF REPEATS FREQUENCY OF DF508 (n p 148) G542X (n p 56) N1303K (n p 17) 21 .993 1 .941 22 0 0 .059 23 .007 0 0 NOTE.-Numbers of chromosomes studied appear in parentheses. Login to comment 51 ABCC7 p.Asn1303Lys ABCC7 p.Gly542* Because no disease chromosomes had yet been typed for the more recently described IVS1CA marker, a total of 126 patients (252 chromosomes), who carried the DF508, G542X, and/or N1303K mutations, were typed for this locus. Login to comment 55 ABCC7 p.Gly551Asp ABCC7 p.Trp1282* We used PHYLIP (Felsenstein 1989) to produce maximum-likelihood population trees of allele frequencies of five polymorphisms (no data were available for IVS1CA, for chromosomes carrying G551D or W1282X) of normal and CF chromosomes. Login to comment 56 ABCC7 p.Gly551Asp ABCC7 p.Trp1282* ABCC7 p.Asn1303Lys ABCC7 p.Gly542* IVS6aGATT, IVS8CA, T854, IVS17bTA, and TUB20 allele frequencies for CF chromosomes (with DF508, G542X, N1303K, G551D, and W1282X mutations) were obtained from the literature (Morral et al. 1994, 1996). Login to comment 58 ABCC7 p.Gly551Asp ABCC7 p.Trp1282* ABCC7 p.Asn1303Lys ABCC7 p.Gly542* Allele frequencies for the intron 1 CA repeat in CF Table 2 Most Frequent CFTR Haplotype(s) for the Five Most Common CF Mutations CF MUTATION HAPLOTYPE(S) AT MARKER a IVS1CA IVS6aGATT IVS8CA T854 IVS17bTA TUB20 DF508 21 6 23/17 1 31/32 2 G542X 21 6 23 1 33/32 2 N1303K 21 6 23/22/24 1 31 2 G551D NA 7 16 2 7 1 W1282X NA 7 17 2 7 1 a IVS1CA was typed in the present study. Login to comment 61 ABCC7 p.Gly551Asp ABCC7 p.Trp1282* Table 4 Frequencies, Normal Chromosomes, of Haplotypes 7-16/17-2-7-1, Associated with CF Mutations G551D and W1282X Population Mean Frequency ‫ע‬ SE (%) Tanzanians 3.2 ‫ע‬ 2.2 Biaka 9 ‫ע‬ 2.6 Mbuti 12 ‫ע‬ 4 Saharawi 20.8 ‫ע‬ 3.9 Druze 15.1 ‫ע‬ 3.2 Yemenites 7.5 ‫ע‬ 2.9 Basques 11.2 ‫ע‬ 2.1 Catalans 16.7 ‫ע‬ 2.9 Finns 16.1 ‫ע‬ 4.7 Russians 15 ‫ע‬ 4.6 Adygei 17.3 ‫ע‬ 3.8 Kazakhs 6.7 ‫ע‬ 3.2 Yakut 2.6 ‫ע‬ 1.8 NOTE.- The frequency in the populations not listed is zero. Login to comment 62 ABCC7 p.Asn1303Lys ABCC7 p.Gly542* Table 3 Frequencies, in Normal Chromosomes, of Haplotypes Associated with CF Mutations DF508, G542X, and N1303K POPULATION MEAN FREQUENCY (SE) IN HAPLOTYPE (%)a A B C D Druze 2.4 ‫ע‬ 1.4 0 4 ‫ע‬ 1.7 0 Basque 0 0 4.2 ‫ע‬ 1.4 0 Catalan 0 0 1.4 ‫ע‬ .9 .6 ‫ע‬ .6 Finnish 0 1.6 ‫ע‬ 1.6 3.2 ‫ע‬ 2.2 1.6 ‫ע‬ 1.6 Russian 0 0 1.7 ‫ע‬ 1.7 1.7 ‫ע‬ 1.7 Adygei 0 0 2.0 ‫ע‬ 1.4 0 Japanese 0 0 0 1.2 ‫ע‬ 1.2 NOTE.-The frequency in the populations not listed is zero. Login to comment 66 ABCC7 p.Gly551Asp ABCC7 p.Trp1282* ABCC7 p.Asn1303Lys ABCC7 p.Gly542* When all six markers are considered in their chromosomal order (i.e., IVS1CA, IVS6aGATT, IVS8CA, T854, IVS17bTA, and TUB20), these haplotype background groups are: (1) 21-6-(17/22/23/24)-1-(31/32/33)-2, of which the most frequent are 21-6-23-1-31-2 (for DF508 and N1303K mutations) and 21-6-23-1-33-2 (for the G542X mutation) it is evident that these three different CF mutations (which have independent origins) are found in very closely related haplotypes, since they differ only by a few repeat units at the fast-evolving STRP sites; and (2) 7-(16/17)-2-7-1, in which G551D and W1282X are found. Login to comment 72 ABCC7 p.Asn1303Lys ABCC7 p.Gly542* Haplotypes associated with CF mutations G542X and N1303K are closely related to those of DF508, and the situation is therefore similar. Login to comment 77 ABCC7 p.Gly551Asp ABCC7 p.Trp1282* ABCC7 p.Asn1303Lys ABCC7 p.Gly542* Thus, haplotypes found at frequencies of the same order Figure 3 Maximum-likelihood tree of allele frequencies of five loci (IVS6aGATT, IVS8CA, T854, IVS17bTA and TUB20) among normal chromosomes, from worldwide populations, and among CF chromosomes (DF508, G542X, N1303K, G551D and W1282X chromosomes). Login to comment 85 ABCC7 p.Gly551Asp ABCC7 p.Trp1282* The situation is very different for the two other frequent mutations (G551D and W1282X). Login to comment 90 ABCC7 p.Gly551Asp ABCC7 p.Trp1282* ABCC7 p.Asn1303Lys ABCC7 p.Gly542* Thus, it appears that DF508, G542X, and N1303K are closely related to each other, as are G551D and W1282X, independently of the population from which chromosomes were sampled. Login to comment 94 ABCC7 p.Asn1303Lys ABCC7 p.Gly542* Although no population has them in frequencies high enough to suggest a likely place of origin, it should be kept in mind that mutations DF508, G542X, and N1303K are independent unique events and that their occurrence in a similar background gives support to the hypothesis that the three mutations arose in a single population in which these haplotypes were frequent. Login to comment 96 ABCC7 p.Gly551Asp ABCC7 p.Trp1282* The current widespread distribution of haplotypes related to G551D and W1282X is compatible with an origin in Europe, although a geographic distribution that would allow us to identify the birthplace of these mutations is not evident. Login to comment