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Advisor(s)
Abstract(s)
This study aimed to identify genetic markers in the HBB Cluster; HBS1L-MYB intergenic region; and BCL11A, KLF1, FOX3, and ZBTB7A genes associated with the heterogeneous phenotypes of Sickle Cell Anemia (SCA) using the next-generation sequencing, as well as to assess their influence and prevalence in an Angolan population. Hematological, biochemical, and clinical data were considered to determine patients’ severity phenotypes. Samples from 192 patients were sequenced, and 5,019,378 variants of high quality were registered. A catalog of candidate modifier genes that clustered in pathophysiological pathways important for SCA was generated, and candidate genes associated with increasing vaso-occlusive crises (VOC) and with lower fetal hemoglobin (HbF) were identified. These data support the polygenic view of the genetic architecture of SCA phenotypic variability. Two single nucleotide polymorphisms in the intronic region of 2q16.1, harboring the BCL11A gene, are genome-wide and significantly associated with decreasing HbF. A set of variants was identified to nominally be associated with increasing VOC and are potential genetic modifiers harboring phenotypic variation among patients. To the best of our knowledge, this is the first investigation of clinical variation in SCA in Angola using a well-customized and targeted sequencing approach.
Description
This research was funded by FCT/Aga Khan (project nº330842553) and FCT/MCTES
(UIDB/05608/2020 and UIDP/05608/2020) – H&TRC.
Keywords
Sickle cell anemia Next-generation sequencing NGS Children Angola FCT/Aga Khan_Project nº 330842553 FCT_UIDB/05608/2020 FCT_UIDP/05608/2020
Citation
Ginete C, Delgadinho M, Santos B, Silva C, Guerreiro P, Brito M, et al. Genetic modifiers of sickle cell anemia phenotype in a cohort of Angolan children. Genes. 2024;15(4):469.
Publisher
MDPI