Towards genomic medicine: a tailored next-generation sequencing panel for hydroxyurea pharmacogenomics in Tanzania.

IF 2.1 4区 医学 Q3 GENETICS & HEREDITY BMC Medical Genomics Pub Date : 2024-07-18 DOI:10.1186/s12920-024-01924-5
Siana Nkya, Collin Nzunda, Emmanuel Saukiwa, Frida Kaywanga, Eliud Buberwa, David Solomon, Heavenlight Christopher, Doreen Ngowi, Julieth Johansen, Florence Urio, Josephine Mgaya, Salman Karim, Mohamed Zahir Alimohamed, Raphael Z Sangeda, Clara Chamba, Emile R Chimusa, Enrico Novelli, Julie Makani
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Abstract

Background: Pharmacogenomics of hydroxyurea is an important aspect in the management of sickle cell disease (SCD), especially in the era of genomic medicine. Genetic variations in loci associated with HbF induction and drug metabolism are prime targets for hydroxyurea (HU) pharmacogenomics, as these can significantly impact the therapeutic efficacy and safety of HU in SCD patients.

Methods: This study involved designing of a custom panel targeting BCL11A, ARG2, HBB, HBG1, WAC, HBG2, HAO2, MYB, SAR1A, KLF10, CYP2C9, CYP2E1 and NOS1 as potential HU pharmacogenomics targets. These genes were selected based on their known roles in HbF induction and HU metabolism. The panel was designed using the Illumina Design Studio (Illumina, San Diego, CA, USA) and achieved a total coverage of 96% of all genomic targets over a span of 51.6 kilobases (kb). This custom panel was then sequenced using the Illumina MiSeq platform to ensure high coverage and accuracy.

Results: We are reporting a successfully designed Illumina (MiSeq) HU pharmacogenomics custom panel encompassing 51.6 kilobases. The designed panel achieved greater than 1000x amplicon coverage which is sufficient for genomic analysis.

Conclusions: This study provides a valuable tool for research in HU pharmacogenomics, especially in Africa where SCD is highly prevalent, and personalized medicine approaches are crucial for improving patient outcomes. The custom-designed Illumina (MiSeq) panel, with its extensive coverage and high sequencing depth, provides a robust platform for studying genetic variations associated with HU response. This panel can contribute to the development of tailored therapeutic strategies, ultimately enhancing the management of SCD through more effective and safer use of hydroxyurea.

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迈向基因组医学:为坦桑尼亚羟基脲药物基因组学量身定制的下一代测序面板。
背景:羟基脲的药物基因组学是镰状细胞病(SCD)治疗的一个重要方面,尤其是在基因组医学时代。与 HbF 诱导和药物代谢相关的基因位点的遗传变异是羟基脲(HU)药物基因组学研究的主要目标,因为这些位点会显著影响 HU 在 SCD 患者中的疗效和安全性:这项研究包括设计一个定制的基因组,将 BCL11A、ARG2、HBB、HBG1、WAC、HBG2、HAO2、MYB、SAR1A、KLF10、CYP2C9、CYP2E1 和 NOS1 作为潜在的 HU 药物基因组学靶点。选择这些基因的依据是它们在 HbF 诱导和 HU 代谢中的已知作用。面板是使用 Illumina Design Studio(Illumina,美国加利福尼亚州圣迭戈)设计的,在 51.6 千碱基(kb)的跨度内,所有基因组靶标的总覆盖率达到 96%。然后使用 Illumina MiSeq 平台对这一定制面板进行测序,以确保高覆盖率和准确性:我们报告了一个成功设计的Illumina(MiSeq)HU药物基因组学定制面板,涵盖51.6千碱基。所设计的面板实现了超过 1000 倍的扩增子覆盖率,足以进行基因组分析:这项研究为HU药物基因组学研究提供了宝贵的工具,尤其是在SCD高发的非洲地区,个性化医疗方法对改善患者预后至关重要。定制设计的Illumina(MiSeq)面板覆盖面广、测序深度高,为研究与HU反应相关的基因变异提供了一个强大的平台。该研究小组有助于开发量身定制的治疗策略,通过更有效、更安全地使用羟基脲,最终提高 SCD 的治疗效果。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
BMC Medical Genomics
BMC Medical Genomics 医学-遗传学
CiteScore
3.90
自引率
0.00%
发文量
243
审稿时长
3.5 months
期刊介绍: BMC Medical Genomics is an open access journal publishing original peer-reviewed research articles in all aspects of functional genomics, genome structure, genome-scale population genetics, epigenomics, proteomics, systems analysis, and pharmacogenomics in relation to human health and disease.
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