Incidence of haemoglobinopathies in various populations - The impact of immigration
ABSTRACT The aim of this study was to update the incidence data of beta thalassaemia mutations in various populations and compare it to the spectrum of mutations in the United Kingdom (UK) population in order to determine the impact of immigration.
Published data for the beta-thalassaemia mutation spectrum and allele frequencies for 60 other countries was updated and collated into regional tables. The beta-thalassaemia mutations in the UK population have been characterised in 1712 unrelated carriers referred for antenatal screening. Similarly, the alpha-thalassaemia mutations in the UK population have been characterised in 2500 possible alpha-thalassaemia carriers.
A total of 68 different beta-thalassaemia mutations were identified in couples requiring screening for antenatal diagnosis in the UK population. Of these mutations, 59 were found in immigrants to the UK, from all major ethnic groups with a high incidence of haemoglobinopathies. A total of 40 different alpha-thalassaemia mutations were characterised in the UK population. Ten deletion mutations were identified, including all the Southeast Asian and Mediterranean alpha(0)-thalassaemia mutations. In addition, 30 non-deletion alpha(+)-thalassaemia mutations were discovered, accounting for 46% of the worldwide known non-deletion mutations.
The impact of immigration has resulted in the UK population having a higher number of beta-thalassaemia mutations and alpha-thalassaemia mutations than any of the 60 other countries with a published spectrum of mutations, including both endemic countries and the non-endemic countries of Northern Europe. The racial heterogeneity of the immigrant population in a non-endemic country significantly increases the spectrum of haemoglobinopathy mutations and their combinations found in individuals, making the provision of a molecular diagnostic prenatal diagnosis service more challenging.
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ABSTRACT: Endemic diseases are caused by environmental and genetic factors. While in this special issue several chapters deal with environmental factors, including infections, the present focus is on genetic causes of disease clustering due to inbreeding and recessive disease mechanisms. Consanguinity is implying sharing of genetic heritage because of marriage between close relatives originating from a common ancestor. With limited natural selection, recessive genes may become more frequent in an inbred compared with an outbred population. Consanguinity is common in North Africa (NA), and the estimates range from 40 to 49% of all marriages in Tunisia and 29-33% in Morocco. As a consequence, recessive disorders are common in the NA region, and we give some examples. Thalassaemia and sickle cell disease/anaemia constitute the most common inherited recessive disorders globally and they are common in NA, but with immigration they have spread to Europe and to other parts of the world. Another example is familial Mediterranean fever, which is common in the Eastern Mediterranean area. With immigrantion from that area to Sweden, it has become the most common hereditary autoinflammatory disease in that country, and there is no evidence that any native Swede would have been diagnosed with this disease. The examples discussed in this chapter show that the historic movement of populations and current immigration are influencing the concept of 'endemic' disease.The European Journal of Public Health 08/2014; 24(suppl 1):57-63. DOI:10.1093/eurpub/cku104 · 2.46 Impact Factor
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ABSTRACT: Hemoglobinopathies constitute the most common monogenic disorders worldwide, caused by mutations in the globin genes that synthesize the globin chains of hemoglobin. Synthesis may be reduced (thalassemia) or underlie abnormal hemoglobins. Mutation interactions produce a wide range of disorders. For neonatal and antenatal screening, identification of affected newborns or carriers is achieved by hematological tests. DNA analysis supports definitive diagnosis, and additionally facilitates prenatal diagnosis procedures. Most methods used today have been developed over several decades, with few recent advances in hematology methods. However, DNA methods evolve continuously. With global migration and multiethnic societies the trend is from targeted, population-specific methods towards generic methods, such as Sanger sequencing (point mutations) and multiplex ligation probe amplification (deletions). DNA microarrays constitute an advanced DNA method for some mutation categories. The newest DNA technology is next-generation sequencing. Although not completely ready for routine use currently, next-generation sequencing may soon become a reality for some hemoglobin diagnostic laboratories.Biomarkers in Medicine 01/2014; 8(1):119-31. DOI:10.2217/bmm.13.103 · 2.86 Impact Factor
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ABSTRACT: Inherited haemoglobinopathies are the most common monogenic diseases, with millions of carriers and patients worldwide. At present, we know several hundred disease-causing mutations on the globin gene clusters, in addition to numerous clinically important trans-acting disease modifiers encoded elsewhere and a multitude of polymorphisms with relevance for advanced diagnostic approaches. Moreover, new disease-linked variations are discovered every year that are not included in traditional and often functionally limited locus-specific databases. This paper presents IthaGenes, a new interactive database of haemoglobin variations, which stores information about genes and variations affecting haemoglobin disorders. In addition, IthaGenes organises phenotype, relevant publications and external links, while embedding the NCBI Sequence Viewer for graphical representation of each variation. Finally, IthaGenes is integrated with the companion tool IthaMaps for the display of corresponding epidemiological data on distribution maps. IthaGenes is incorporated in the ITHANET community portal and is free and publicly available at http://www.ithanet.eu/db/ithagenes.PLoS ONE 07/2014; 9(7):e103020. DOI:10.1371/journal.pone.0103020 · 3.53 Impact Factor