CTGA: the database for genetic disorders in Arab populations

The Arabs comprise a genetically heterogeneous group that resulted from the admixture of different populations throughout history. They share many common characteristics responsible for a considerable proportion of perinatal and neonatal mortalities. To this end, the Centre for Arab Genomic Studies (CAGS) launched a pilot project to construct the ‘Catalogue of Transmission Genetics in Arabs’ (CTGA) database for genetic disorders in Arabs. Information in CTGA is drawn from published research and mined hospital records. The database offers web-based basic and advanced search approaches. In either case, the final search result is a detailed HTML record that includes text-, URL- and graphic-based fields. At present, CTGA hosts entries for 692 phenotypes and 235 related genes described in Arab individuals. Of these, 213 phenotypic descriptions and 22 related genes were observed in the Arab population of the United Arab Emirates (UAE). These results emphasize the role of CTGA as an essential tool to promote scientific research on genetic disorders in the region. The priority of CTGA is to provide timely information on the occurrence of genetic disorders in Arab individuals. It is anticipated that data from Arab countries other than the UAE will be exhaustively searched and incorporated in CTGA ()

Consanguinity and reproductive health among Arabs

Consanguineous marriages have been practiced since the early existence of modern humans. Until now consanguinity is widely practiced in several global communities with variable rates depending on religion, culture, and geography. Arab populations have a long tradition of consanguinity due to socio-cultural factors. Many Arab countries display some of the highest rates of consanguineous marriages in the world, and specifically first cousin marriages which may reach 25-30% of all marriages. In some countries like Qatar, Yemen, and UAE, consanguinity rates are increasing in the current generation. Research among Arabs and worldwide has indicated that consanguinity could have an effect on some reproductive health parameters such as postnatal mortality and rates of congenital malformations. The association of consanguinity with other reproductive health parameters, such as fertility and fetal wastage, is controversial. The main impact of consanguinity, however, is an increase in the rate of homozygotes for autosomal recessive genetic disorders. Worldwide, known dominant disorders are more numerous than known recessive disorders. However, data on genetic disorders in Arab populations as extracted from the Catalogue of Transmission Genetics in Arabs (CTGA) database indicate a relative abundance of recessive disorders in the region that is clearly associated with the practice of consanguinity

Brief Communications: Rare β-Thalassemia Mutation in a Turkish Patient: FSC-36/37 (-T)

We describe the rare /7-thalassemia mutation at codons 36/37 (-T) for the first time in Turkey. The propositus is a Turkish patient with /^-thalassemia major who originated in Adana but now resides in Istanbul. Molecular analysis revealed a compound heterozygosity for the common eastern Mediterranean mutation IVS-I-110 (G-A) along with mutation FSC-36/37 (-T). The FSC-36/37 (-T) mutation could have arisen somewhere in the region, including northern Iran and the inaccessible mountainous region of eastern Anatolia. The mutation could have followed two migration routes during the time of Ottoman rule, the first being to Azerbaijan and the second, probably a more recent one, passing through southeastern Anatolia and reaching southern Bulgaria

History and Origin of ß-Thalassemia in Turkey: Sequence Haplotype Diversity of ß-Globin Genes

In the present study we report the sequence haplotypes associated with 22 b-globin gene mutations present in Turkey. Nine nucleotide polymorphisms and an (AT)xTy motif located at the 5¢ end of the b-globin gene form the sequence haplotypes that were investigated in 204 unrelated b- thalassemia and wild-type chromosomes from Turkey. Twelve sequence haplotypes were observed in the chromosomes analyzed and haplotypic heterogeneity was found in the wild-type b-globin genes. Samples from the Black Sea region demonstrated a remarkable level of haplotypic heterogeneity in contrast to the homogeneity present in Central Anatolian samples. Of the 22 b-globin mutations analyzed, 18 were related with single sequence haplotypes. This simple association led to the attempt to determine the origin of these mutations by comparing their frequencies in Turkey with those in other countries and/or the world distribution of the haplotypes carrying them. However, the presence of several exceptions for the “one haplotype/one mutation” rule showed that the b-globin gene cluster is far from static. Each of the IVS-I-110 (G!A), Cd 39 (C!T), IVS-I-6 (T!C), and –30 (T!A) b- globin mutations was associated with a minimum of two sequence haplotypes. This fact is best explained by the likelihood of strong recombination mechanisms taking place, rather than by assuming multiple origins for each of these alleles. According to our results, malarial selection for the oldest b- thalassemia allele in Anatolia (i.e., IVS-I-110 G!A) may have occurred between 6500 and 2000 b.c. From that date on, most of the common b-thalassemia mutations in Turkey were established, and by the 13th century a.d. most of them were brought to frequencies close to those observed at present

History and Origin of β-Thalassemia in Turkey: Sequence Haplotype Diversity of β-Globin Genes

Abstract In the present study we report the sequence haplotypes associated with 22 β-globin gene mutations present in Turkey. Nine nucleotide polymorphisms and an (AT) x T y motif located at the 5′ end of the β-globin gene form the sequence haplotypes that were investigated in 204 unrelated β-thalassemia and wild-type chromosomes from Turkey. Twelve sequence haplotypes were observed in the chromosomes analyzed and haplotypic heterogeneity was found in the wild-type β-globin genes. Samples from the Black Sea region demonstrated a remarkable level of haplotypic heterogeneity in contrast to the homogeneity present in Central Anatolian samples. Of the 22 β-globin mutations analyzed, 18 were related with single sequence haplotypes. This simple association led to the attempt to determine the origin of these mutations by comparing their frequencies in Turkey with those in other countries and/or the world distribution of the haplotypes carrying them. However, the presence of several exceptions for the "one haplotype/one mutation" rule showed that the β-globin gene cluster is far from static. Each of the IVS-I-110 (G→A), Cd 39 (C→T), IVS-I-6 (T→C), and -30 (T→A) β-globin mutations was associated with a minimum of two sequence haplotypes. This fact is best explained by the likelihood of strong recombination mechanisms taking place, rather than by assuming multiple origins for each of these alleles. According to our results, malarial selection for the oldest β-thalassemia allele in Anatolia (i.e., IVS-I-110 G→A) may have occurred between 6500 and 2000 b.c. From that date on, most of the common β-thalassemia mutations in Turkey were established, and by the 13th century a.d. most of them were brought to frequencies close to those observed at present. β-thalassemia is an autosomal recessive disorder characterized by microcytosis and hemolytic anemia resulting from a variety of molecular defects that intervene with the normal synthesis of the β-globin chains of hemoglobi

Identification of the Chinese IVS-II-654 (C --\u3e ) β-Thalassemia Mutation in an Immigrant Turkis Family: Recurrence of Migration?

In this study we describe the Chinese IVS-II-654 (C--\u3eT) β-thalassemia mutation for the first time in an immigrant Turkish family living in Istanbul and originating from Xanthe, Greece. Four members of the family, representing 3 generations, are heterozygous for this mutation. A detailed family history demonstrated a Greek origin for members of 5 generations with no records of migration or consanguineous marriages. Analysis of polymorphic nucleotides located at the 5\u27 end of the β-globin chromosomes bearing the IVS-II-654 mutation in the family described carried the (AT)9(T)5 type of microsatellite sequence and the ACATCCCCA haplotype. These 2 haplotype components favor a non-Eastern Asian origin for this chromosome, hence suggesting an independent origin for the IVS-II-654 mutation described in this family

Human variome project country nodes: Documenting genetic information within a country

The Human Variome Project (http://www.humanvariomeproject.org) is an international effort aiming to systematically collect and share information on all human genetic variation. The two main pillars of this effort are gene/disease specific databases and a network of Human Variome Project Country Nodes. The latter are nationwide efforts to document the genomic variation reported within a specific population. The development and successful operation of the Human Variome Project Country Nodes are of utmost importance to the success of Human Variome Project aims and goals, since they not only allow the genetic burden of disease to be quantified in different countries, but also provide diagnosticians and researchers access to an up-to date resource that will assist them in their daily clinical practice and biomedical research, respectively. Here, we report the discussions and recommendations that resulted from the inaugural meeting of the International Confederation of Countries Advisory Council, held on December 12th, 2011, during the 2011 Human Variome Project Beijing Meeting. We discuss the steps necessary to maximize the impact of the Country Node effort for developing regional and country-specific clinical genetics resources and summarize a few well-coordinated genetic data collection initiatives that would serve as paradigms for similar projects.status: publishe

Human variome project country nodes: Documenting genetic information within a country

The Human Variome Project (http://www.humanvariomeproject.org) is an international effort aiming to systematically collect and share information on all human genetic variation. The two main pillars of this effort are gene/disease-specific databases and a network of Human Variome Project Country Nodes. The latter are nationwide efforts to document the genomic variation reported within a specific population. The development and successful operation of the Human Variome Project Country Nodes are of utmost importance to the success of Human Variome Project's aims and goals because they not only allow the genetic burden of disease to be quantified in different countries, but also provide diagnosticians and researchers access to an up-to-date resource that will assist them in their daily clinical practice and biomedical research, respectively. Here, we report the discussions and recommendations that resulted from the inaugural meeting of the International Confederation of Countries Advisory Council, held on 12th December 2011, during the 2011 Human Variome Project Beijing Meeting. We discuss the steps necessary to maximize the impact of the Country Node effort for developing regional and country-specific clinical genetics resources and summarize a few well-coordinated genetic data collection initiatives that would serve as paradigms for similar projects. Hum Mutat 33:15131519, 2012. (c) 2012 Wiley Periodicals, Inc