The origin of the major cystic fibrosis mutation (ΔF508) in European populations

Morral, Núria; Bertranpetit, Jaume; Estivill, Xavier; Nunes, Virginia; Casals, Teresa; Giménez, Joaquím; Reis, André; Varon-Mateeva, Raymonda; Maçek, Milan; Kalaydjieva, Luba; Angelicheva, Dora; Dancheva, R.; Romeo, Giovanni; Russo, Maria Pia; Garnerone, S; Restagno, Gabriella; Ferrari, Maurizio; Magnani, Carmelina; Claustres, Mireille; Desgeorges, Marie; Schwartz, Marianne; Schwarz, Martin; Dallapiccola, Bruno; Novelli, Giuseppe; Férec, Claude; Arce, M. De; Németi, M; Kere, Juha; Anvret, Maria; Dahl, Niklas; Kádasi, L

doi:10.1038/ng0694-169

Cited by 325 publications

(244 citation statements)

References 23 publications

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“…The opposite was seen in Chilean ΔF508 chromosomes in our study, with over 90% of them present on XK haplotype B. This finding evidences marked linkage disequilibrium between them, as it has been shown in other populations Highsmith et al, 1990;Dork et al, 1992;Morral, Bertranpetit et al, 1994). A European origin for the ΔF508 mutation observed in Chilean patients is therefore suggested.…”

Section: Discussionsupporting

confidence: 66%

“…Subsequent research confirmed that this observation reflected the presence of strong linkage disequilibrium, that is, non-random association of alleles at two or more loci on a chromosome, between the most common European mutation, deltaF508 (ΔF508), and haplotype B. This finding supported the theory of a single origin of this mutation (Dork et al, 1992;Highsmith et al, 1990;Morral, Bertranpetit et al, 1994). Several other common mutations are predominantly present on one haplotype.…”

Section: Introductionsupporting

confidence: 71%

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XV-2c and KM: 19 haplotype analysis in Chilean patients with cystic fibrosis and unknown CFTR gene mutations

2007

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Cystic fibrosis (CF) is caused by mutations in the CFTR gene. More than 1600 mutations have been described, with frequencies that differ worldwide according to the ethnic origin of patients. A small group of mutations are recurrent on several populations. It has been shown that they each tend occur on specific chromosome 7 haplotypes, supporting the notion of a single origin for them. Less than 50% of mutations in Chilean patients have been identified to date. To indirectly assess the possible presence of a predominant founder mutation in the remaining unknown alleles, we evaluated 2 polymorphic markers, XV-2c and KM.19, tightly linked to the CFTR locus. The study was done in Chilean CF patients with unknown or deltaF508 (ΔF508) CFTR mutations and their haplotypes were compared to affected family-based controls. ΔF508 showed marked linkage disequilibrium with XV-2c/KM.19 haplotype B, with 90% of alleles on that haplotype. There was no difference in haplotype distribution between unknown mutations and normal controls. These results support a European origin for ΔF508 alleles in Chilean patients, and make unlikely the presence of a predominant founder mutation in the so-far unknown alleles.

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Section: Discussionsupporting

confidence: 66%

Section: Introductionsupporting

confidence: 71%

XV-2c and KM: 19 haplotype analysis in Chilean patients with cystic fibrosis and unknown CFTR gene mutations

2007

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“…The high frequency and distribution of the IVS8-1G > C mutation could reflect migrations and/or replacement of ancient European populations carrying this mutation, as has been suggested for the ∆F508 mutation causing cystic fibrosis. 30 In support of the notion that the IVS8-1G > C is old is our previous observation that two SLOS chromosomes carried two different mutations. Both double mutant alleles involved the IVS8-1G > C site together with either R352Q (which is rare) or T93M which is frequent in Italy.…”

Section: Discussionmentioning

confidence: 54%

Frequency gradients of DHCR7 mutations in patients with Smith-Lemli-Opitz syndrome in Europe: evidence for different origins of common mutations

et al. 2001

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“…The dating method employed (Morral et al 1994;Saillard et al 2000) is based on the average number of mutations accumulated from an ancestral sequence as a linear function of time and mutation rate. This method was also performed with the Network 3.0 program.…”

Section: Phylogenetic Analysismentioning

confidence: 99%

Joining the Pillars of Hercules: mtDNA Sequences Show Multidirectional Gene Flow in the Western Mediterranean

Plaza

Calafell

Helal

et al. 2003

Annals of Human Genetics

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122

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SummaryPhylogenetic analysis of mitochondrial DNA (mtDNA) performed in Western Mediterranean populations has shown that both shores share a common set of mtDNA haplogroups already found in Europe and the Middle East. Principal co-ordinates of genetic distances and principal components analyses based on the haplotype frequencies show that the main genetic difference is attributed to the higher frequency of sub-Saharan L haplogroups in NW Africa, showing some gene flow across the Sahara desert, with a major impact in the southern populations of NW Africa. The AMOVA demonstrates that SW European populations are highly homogeneous whereas NW African populations display a more heterogeneous genetic pattern, due to an east-west differentiation as a result of gene flow coming from the East. Despite the shared haplogroups found in both areas, the European V and the NW African U6 haplogroups reveal the traces of the Mediterranean Sea permeability to female migrations, and allowed for determination and quantification of the genetic contribution of both shores to the genetic landscape of the geographic area.Comparison of mtDNA data with autosomal markers and Y-chromosome lineages, analysed in the same populations, shows a congruent pattern, although female-mediated gene flow seems to have been more intense than male-mediated gene flow.

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The origin of the major cystic fibrosis mutation (ΔF508) in European populations

Cited by 325 publications

References 23 publications

XV-2c and KM: 19 haplotype analysis in Chilean patients with cystic fibrosis and unknown CFTR gene mutations

XV-2c and KM: 19 haplotype analysis in Chilean patients with cystic fibrosis and unknown CFTR gene mutations

Frequency gradients of DHCR7 mutations in patients with Smith-Lemli-Opitz syndrome in Europe: evidence for different origins of common mutations

Joining the Pillars of Hercules: mtDNA Sequences Show Multidirectional Gene Flow in the Western Mediterranean

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