Path to Facilitate the Prediction of Functional Amino Acid Substitutions in Red Blood Cell Disorders – A Computational Approach

A major area of effort in current genomics is to distinguish mutations that are functionally neutral from those that contribute to disease. Single Nucleotide Polymorphisms (SNPs) are amino acid substitutions that currently account for approximately half of the known gene lesions responsible for human inherited diseases. As a result, the prediction of non-synonymous SNPs (nsSNPs) that affect protein functions and relate to disease is an important task.In this study, we performed a comprehensive analysis of deleterious SNPs at both functional and structural level in the respective genes associated with red blood cell metabolism disorders using bioinformatics tools. We analyzed the variants in Glucose-6-phosphate dehydrogenase (G6PD) and isoforms of Pyruvate Kinase (PKLR & PKM2) genes responsible for major red blood cell disorders. Deleterious nsSNPs were categorized based on empirical rule and support vector machine based methods to predict the impact on protein functions. Furthermore, we modeled mutant proteins and compared them with the native protein for evaluation of protein structure stability.We argue here that bioinformatics tools can play an important role in addressing the complexity of the underlying genetic basis of Red Blood Cell disorders. Based on our investigation, we report here the potential candidate SNPs, for future studies in human Red Blood Cell disorders. Current study also demonstrates the presence of other deleterious mutations and also endorses with in vivo experimental studies. Our approach will present the application of computational tools in understanding functional variation from the perspective of structure, expression, evolution and phenotype

Mild clinical expression of S-beta thalassemia in a Brazilian patient with the beta(+) IVS-I-6 (T -> C) mutation

We report on an eight-year-old Brazilian girl with S-beta(+) thalassemia. The patient had a steady 10.1 g/dl hemoglobin with 57% HbS. Direct sequence analysis of beta-globin gene showed her to be heterozygous for the IVS-I-6 (T-->C) mutation. This beta(+) thalassemia mutation, sometimes referred to as the Portuguese type, was found to be associated with the C-->T polymorphism at codon 2. In combination with the beta(S) gene, this mutation results in very mild sickle cell disease symptoms.21443143

Mild Clinical Expression Of S-β Thalassemia In A Brazilian Patient With The β+ Ivs-i-6 (t→c) Mutation

We report on an eight-year-old Brazilian girl with S-β+ thalassemia. The patient had a steady 10.1 g/dl hemoglobin with 57% HbS. Direct sequence analysis of β-globin gene showed her to be heterozygous for the IVS-I-6 (T→C) mutation. This β+ thalassemia mutation, sometimes referred to as the Portuguese type, was found to be associated with the C→T polymorphism at codon 2. In combination with the β(s) gene, this mutation results in very mild sickle cell disease symptoms.214431433Antonarakis, S.E., Orkin, S.H., Cheng, T.C., Scott, A.F., Sexton, J.P., Trusko, S., Charache, S., Kazazian Jr., H.H., β Thalassemia in American blacks: Novel mutations in the "TATA" box and an acceptor splice site (1984) Proc. Natl. Acad. Sci. USA, 81, pp. 1154-1158Atweh, G., Forget, B.G., Identification of a β-thalassemia mutation associated with a novel haplotype of RFLPs (1986) Am. J. Hum. Genet., 38, pp. 855-859Baysal, E., Huisman, T.H.J., Detection of common deletional α-thalassemia-2 determinants by PCR (1994) Am. J. Hematol., 46, pp. 208-213Bunn, H.F., Forget, B.G., (1986) Hemoglobin: Molecular, Genetic and Clinical Aspects, , W.B. Saunders Company, PhiladelphiaMartins, C.S.B., Ramalho, A.S., Sonati, M.F., Gonçalves, M.S., Costa, F.F., Molecular characterisation of β thalassaemia heterozygotes in Brazil (1993) J. Med. Genet., 30, pp. 797-798Orkin, S.H., Kazazian Jr., H.H., Antonarakis, S.E., Goff, S.C., Boehm, C.D., Sexton, J.P., Waber, P.G., Giardina, P.J.V., Linkage of β-thalassemia mutations and β-globin gene polymorphisms with DNA polymorphisms in human β-globin gene cluster (1982) Nature, 296, pp. 627-631Treisman, R., Orkin, S.H., Maniatis, T., Specific transcription and RNA splicing defects in five cloned β-thalassaemia genes (1983) Nature, 302, pp. 591-596Weatherall, D.J., Clegg, J.B., (1981) The Thalassaemia Syndromes. 3rd Edn., , Blackwell Scientific Publications, OxfordZago, M.A., Costa, F.F., Freitas, T.C., Bottura, C., Clinical, hematological and genetic features of sickle cell anemia and sickle cell-beta thalassemia in a Brazilian population (1980) Clin. Genet., 18, pp. 58-6

Mild clinical expression of S-b thalassemia in a Brazilian patient with the b+ IVS-I-6 (T®C) mutation

We report on an eight-year-old Brazilian girl with S-b+ thalassemia. The patient had a steady 10.1 g/dl hemoglobin with 57% HbS. Direct sequence analysis of b-globin gene showed her to be heterozygous for the IVS-I-6 (T®C) mutation. This b+ thalassemia mutation, sometimes referred to as the Portuguese type, was found to be associated with the C®T polymorphism at codon 2. In combination with the bS gene, this mutation results in very mild sickle cell disease symptoms.Nós caracterizamos a base molecular da talassemia b em uma paciente negra brasileira, de 8 anos de idade, com um quadro clínico extremamente benigno de S-b+ talassemia. A paciente tinha uma hemoglobina total de 10,1 g/dl, com 57% de HbS. O sequenciamento direto do DNA, amplificado por PCR, revelou que a paciente é heterozigota da mutação b+ IVS-I-6 (T®C). Esta mutação, algumas vezes referida como o tipo português de talassemia, foi encontrada em associação com o polimorfismo C®T no codon 2 do gene b e, de nosso conhecimento, não havia sido previamente descrita na população negra brasileira.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

AFTER 16 YEARS: AN UPDATE CHECKLIST OF HERPETOFAUNA ON THE NATUNA ISLANDS, INDONESIA

Since the last list of amphibians and reptiles of the Natuna Islands was published nearly 20 years ago, here we provide an updated species list of the herpetofauna of these remote Indonesian islands. We compiled and summarized data from the available literature, and from our own studies conducted in 2011, 2012, 2013, 2017, and 2019. In total, 120 species of amphibians and reptiles were recorded for the Natuna Islands, which included 28 new records and six endemics. Over the past eight years, four species new to science were described from these islands, and they are: Cnemaspis mumpuniae, Cnemaspis sundainsula, Cyrtodactylus hikidai, and Cyrtodactylus rosichonariefi