title: Confirmation of a founder effect in a Northern European population of a new β-globin variant: HBB:c.23_26dup (codons 8/9 (+AGAA)).
abstract: β-Thalassemia is a genetic disease caused by a defect in the production of the β-like globin chain. More than 200 known different variants can lead to the disease and are mainly found in populations that have been exposed to malaria parasites. We recently described a duplication of four nucleotides in the first exon of β-globin gene in several families of patients living in Nord-Pas-de-Calais (France). Using the genotypes at 12 microsatellite markers surrounding the β-globin gene of four unrelated variant carriers plus an additional one recently discovered, we found that they shared a common haplotype indicating a founder effect that was estimated to have taken place 225 years ago (nine generations). In order to determine whether this variant arose in this region of Northern Europe or was introduced by migrants from regions of the world where thalassemia is endemic, we genotyped the first 4 unrelated variant carriers and 32 controls from Nord-Pas-de-Calais for 97 European ancestry informative markers (EAIMs). Using these EAIMs and comparing with population reference panels, we demonstrated that the variant carriers were very similar to the controls and were closer to North European populations than to South European or Middle-East populations. Rare β-thalassemia variants have already been described in patients sampled in non-endemic regions, but it is the first proof of a founder effect in Northern Europe.
authors.affiliation: 1] Inserm UMR-946, Variabilité Génétique et Maladies Humaines, Institut Universitaire d'Hématologie, Université Paris Diderot, Centre d'Etude du Polymorphisme Humain, Paris, France [2] Eco-Anthropologie et Ethnobiologie, UMR 7206 CNRS, MNHN, Université Paris Diderot, Sorbonne Paris Cite, France [3] Ecole Normale Supérieure de Lyon, Master BioSciences, Lyon, France.
authors.forename: Nina
authors.initials: N
authors.lastname: Marchi
authors.affiliation: 1] Département de Génétique, GHU H. Mondor-A. Chenevier, Créteil, France [2] UPEC and INSERM-IMRB, Créteil, France.
authors.forename: Serge
authors.initials: S
authors.lastname: Pissard
authors.affiliation: Service d'Hématologie, Hôpital St Vincent de Paul, Université Catholique de Lille, GHICL, Lille, France.
authors.forename: Manuel
authors.identifier: 0000000245447661
authors.initials: M
authors.lastname: Cliquennois
authors.affiliation: Département de Génétique, GHU H. Mondor-A. Chenevier, Créteil, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Vasseur
authors.affiliation: Département de Génétique, GHU H. Mondor-A. Chenevier, Créteil, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Le Metayer
authors.affiliation: Service de Biochimie, CHU, Lille Cedex, France.
authors.forename: Claude
authors.initials: C
authors.lastname: Mereau
authors.affiliation: Service des Maladies du Sang, Hôpital Claude Huriez, CHU Lille, Lille, France.
authors.forename: Jean Pierre
authors.initials: JP
authors.lastname: Jouet
authors.affiliation: Service d'Hématologie, Hôpital St Vincent de Paul, Université Catholique de Lille, GHICL, Lille, France.
authors.forename: Anne-France
authors.initials: AF
authors.lastname: Georgel
authors.affiliation: 1] Inserm UMR-946, Variabilité Génétique et Maladies Humaines, Institut Universitaire d'Hématologie, Université Paris Diderot, Centre d'Etude du Polymorphisme Humain, Paris, France [2] Inserm UMR-1078, CHU Morvan, Brest, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Genin
authors.affiliation: Service d'Hématologie, Hôpital St Vincent de Paul, Université Catholique de Lille, GHICL, Lille, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Rose
mesh_terms: D001499:Bayes Theorem; D003062:Codon; D005091:Exons; D018703:Founder Effect; D005602:France; D015870:Gene Expression; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D018895:Microsatellite Repeats; D009154:Mutation; D010375:Pedigree; D055544:beta-Globins / Q000235:genetics*; D017086:beta-Thalassemia / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology
chemical_list: D003062:Codon; D055544:beta-Globins