Development of an assay based on next generation sequencing to evaluate all thalassemia patients

Invitrotek ltd. Sti. (Istanbul, turkey) and pronto diagnostics ltd. (Tel aviv, israel) will collaborate in developing an assay, based on the targeted next generation sequencing to detect mutations in all thalassemia cases.

The haemoglobin disorders (hemoglobinopathies) are a group of autosomal recessive disorders characterized by either reduced synthesis of one or more normal globin chains (the thalassaemias) or the synthesis of a structurally abnormal globin chain (the hemoglobin variants). Thalassaemias are the most common single gene disorders in the world and nearly 7% of the world population is carrier for the disease. The incidences of thalassemias vary among different populations. Both the type of thalassemia and the type of mutations also vary in different populations and geographical regions. Alpha thalassemia, the most common genetic disorder of hemoglobin synthesis, affects up to 5% of the world's population. Deletional type alpha thalassemia is probably the most frequent monogenic disorder worldwide, especially in African, Mediterranean, and Chinese populations. There are four copies of alpha globin genes (HBA). The alpha globin chains are present in both fetal and adult hemoglobin, and as a result the homozygous form of the disease causes intrauterine death. Because of this lethal form, those who survive the disease have less severe complications than beta thalassemia. This lethal form of the disease is common in Southeast Asia and Cyprus. Mutations in beta globin gene (HBB) cause beta thalassemia which results in severe anemia in homozygous and compound heterozygous states. Mediterranean, Middle East, North African and Southeast Asian countries have very high carrier frequencies. In Turkey the overall carrier frequency of beta thalassemia is 4%. Thalassemia is caused by different types of mutations that include substitutions, small deletions, insertions, duplications, large deletions and fusions. Modifier genes also cause a problem with the diagnosis of thalassemia. For example mutations in the HFE gene (hemochromatosis gene) or in the HBA gene affect the severity of beta thalassemia. The total number of mutations in globin genes is 1504 (According to HbVar: A database of Human Hemoglobin Variants and Thalassemias). Of these mutations 1228 are substitution mutations. The total number of deletions is 180 in all globin genes and there are 46 large deletions. Twenty-four of them are in beta cluster and 22 of them are in alpha cluster. 23/24 of beta cluster deletions are larger than 1 kb. All alpha cluster deletions are larger than 1 kb. Many diagnostic techniques are on the market now, but neither of them may detect all type of mutations. We propose a novel and complete diagnostic approach for all types of thalassemias. This diagnostic approach is composed of two components. One of them is targeted Next Generation Sequencing (NGS) application in which all substations, small deletions and insertions in all globin and modifiers genes may be detected and a complementary test to identify larger deletions or insertions (indels) (such as MLPA). The effectiveness and remarkable decline in cost of NGS will make this kit more cost-effective and will enable rapid and economical diagnosis for thalassaemia.
Project ID: 
7 626
Start date: 
Project Duration: 
Project costs: 
2 000 000.00€
Technological Area: 
Diagnostics, Diagnosis
Market Area: 

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