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Confirmation of a founder effect in a Northern European population of a new β-globin variant: HBB:c.23_26dup (codons 8/9 (+AGAA)).

Marchi N, Pissard S, Cliquennois M, Vasseur C, Le Metayer N, Mereau C, Jouet JP, Georgel AF, Genin E, Rose C - Eur. J. Hum. Genet. (2014)

Bottom Line: More than 200 known different variants can lead to the disease and are mainly found in populations that have been exposed to malaria parasites.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.

View Article: PubMed Central - PubMed

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.

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.

No MeSH data available.


Related in: MedlinePlus

Top two PCs of the PCA obtained from the genotypes at the 97 ancestry informative SNPs for the 32 Chtimi controls (in purple) and 4 cases (in orange). The percentage of variance explained by each PC is indicated between brackets in the axe legends. The PCA was performed using SmartPCA11 with the default options.
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fig1: Top two PCs of the PCA obtained from the genotypes at the 97 ancestry informative SNPs for the 32 Chtimi controls (in purple) and 4 cases (in orange). The percentage of variance explained by each PC is indicated between brackets in the axe legends. The PCA was performed using SmartPCA11 with the default options.

Mentions: The single ancestor origin of the variant being established, we were interested in determining the geographic origin of this ancestor. The first point was to confirm that the patients and Chtimi controls formed together a genetically homogeneous group regarding the 97 SNPs they were genotyped for. We found that the cases did not differ from the controls on the first two PCs of the PCA (Figure 1). The Mann–Whitney's test comparing the top two PC values in cases and controls gave P-values of, respectively, 0.75 and 0.39 for the first and second PC.


Confirmation of a founder effect in a Northern European population of a new β-globin variant: HBB:c.23_26dup (codons 8/9 (+AGAA)).

Marchi N, Pissard S, Cliquennois M, Vasseur C, Le Metayer N, Mereau C, Jouet JP, Georgel AF, Genin E, Rose C - Eur. J. Hum. Genet. (2014)

Top two PCs of the PCA obtained from the genotypes at the 97 ancestry informative SNPs for the 32 Chtimi controls (in purple) and 4 cases (in orange). The percentage of variance explained by each PC is indicated between brackets in the axe legends. The PCA was performed using SmartPCA11 with the default options.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4538212&req=5

fig1: Top two PCs of the PCA obtained from the genotypes at the 97 ancestry informative SNPs for the 32 Chtimi controls (in purple) and 4 cases (in orange). The percentage of variance explained by each PC is indicated between brackets in the axe legends. The PCA was performed using SmartPCA11 with the default options.
Mentions: The single ancestor origin of the variant being established, we were interested in determining the geographic origin of this ancestor. The first point was to confirm that the patients and Chtimi controls formed together a genetically homogeneous group regarding the 97 SNPs they were genotyped for. We found that the cases did not differ from the controls on the first two PCs of the PCA (Figure 1). The Mann–Whitney's test comparing the top two PC values in cases and controls gave P-values of, respectively, 0.75 and 0.39 for the first and second PC.

Bottom Line: More than 200 known different variants can lead to the disease and are mainly found in populations that have been exposed to malaria parasites.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.

View Article: PubMed Central - PubMed

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.

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.

No MeSH data available.


Related in: MedlinePlus