Version 1
: Received: 28 February 2021 / Approved: 2 March 2021 / Online: 2 March 2021 (12:30:36 CET)
Version 2
: Received: 1 January 2023 / Approved: 3 January 2023 / Online: 3 January 2023 (08:28:50 CET)
How to cite:
Saha, D.; Pal, D.; Chowdhury, P.K.; Nayek, K.; Chakraborty, G.; Basu, S.; BASU, A. A Family Based Whole Exome Sequence Study to Identify Modifier Genes for Phenotype Heterogeneity Between Severe and Non-Severe Thalassemia Patients. Preprints2021, 2021030088. https://doi.org/10.20944/preprints202103.0088.v2
Saha, D.; Pal, D.; Chowdhury, P.K.; Nayek, K.; Chakraborty, G.; Basu, S.; BASU, A. A Family Based Whole Exome Sequence Study to Identify Modifier Genes for Phenotype Heterogeneity Between Severe and Non-Severe Thalassemia Patients. Preprints 2021, 2021030088. https://doi.org/10.20944/preprints202103.0088.v2
Saha, D.; Pal, D.; Chowdhury, P.K.; Nayek, K.; Chakraborty, G.; Basu, S.; BASU, A. A Family Based Whole Exome Sequence Study to Identify Modifier Genes for Phenotype Heterogeneity Between Severe and Non-Severe Thalassemia Patients. Preprints2021, 2021030088. https://doi.org/10.20944/preprints202103.0088.v2
APA Style
Saha, D., Pal, D., Chowdhury, P.K., Nayek, K., Chakraborty, G., Basu, S., & BASU, A. (2023). A Family Based Whole Exome Sequence Study to Identify Modifier Genes for Phenotype Heterogeneity Between Severe and Non-Severe Thalassemia Patients. Preprints. https://doi.org/10.20944/preprints202103.0088.v2
Chicago/Turabian Style
Saha, D., Surupa Basu and ANUPAM BASU. 2023 "A Family Based Whole Exome Sequence Study to Identify Modifier Genes for Phenotype Heterogeneity Between Severe and Non-Severe Thalassemia Patients" Preprints. https://doi.org/10.20944/preprints202103.0088.v2
Abstract
Thalassemia is a common monogenic autosomal disorder prevalent in India. HbE beta thalassemia is a compound heterozygous state of two different beta globin mutations (HBB), predominant in the Eastern India. In HbE-beta thalassemia (β+/β°) patients, one HBB mutation does not produce any functional protein (β°); another mutation produces a structural altered haemoglobin, variant E (β+). It has been observed that in HbE-beta thalassemia patients with same type of HBB mutations, there exist diverse phenotypic presentation ranging from very severe, with regular transfusion-dependence to clinically non severe requiring very less transfusion or no transfusion. To explore this phenotypic mystery, we performed trio based expanded whole exome sequencing (WES) of two extreme phenotypes of HbE beta thalassemia subjects with similar HBB genotype and their parents. For WES library preparation, Agilent Sure select V6+UTR kit was used and sequencing was done through the Illumina HiSeq 2500 platform. This study aimed to search for de novo or inherited variants associated with the clinical severity. Six significant inherited variants were found in the genes, ATOH8, TTLL4, P2RX7, PRSS54, SLC9C2 and VRK2 in severe subject, however only one significant inherited variant in MTRR gene was found in non-severe subject. Bioinformatic analysis also confirms that each variant significantly changes in respective protein structure. The identified genes were either associated with iron absorption, oxidative stress, hematopoietic stem cell differentiation, structural organization of RBC cytoskeleton or regulating anemia. No significant de novo variant were identified associated with clinical severity. The finding of this study indicates that the combined effect of mutation load in major pathways may responsible for severe phenotype.
Keywords
WES; Thalassemia; phenotype
Subject
Biology and Life Sciences, Biochemistry and Molecular Biology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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Commenter: ANUPAM BASU
Commenter's Conflict of Interests: Author