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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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Background: Fetal haemoglobin (HbF) remains a major sickle cell disease modifier. The mechanism of HbF synthesis has been studied for several decades with the intention of increasing interventions for sickle cell disease (SCD), including drugs. However, the complex mechanism of HbF synthesis is influenced by multiple genetic factors interacting with environmental factors. In order to capture useful genetic information, especially with limited resources, one has to carefully design the study. This includes choosing the relevant participants, the correct phenotyping, the choice of samples, and the right genomic assays. This paper describes the approach undertaken as part of preparations for a reticulocyte transcriptome study intended to discover genes associated with HbF decline in newborns in Tanzania. Results: Of the 152 newborns enrolled in the larger study, 40 babies were selected for the reticulocyte transcriptome study based on their HbF levels at birth and later stage of life. Of these, 30 individuals were included under the category of high HbF levels ranging from 72.6-90% and the remaining 10 under the category of low HbF levels ranging from 5.9 - 10.3%. The reticulocyte enrichment recovery purity ranged from 85% - 97%. The total RNA concentrations obtained were >250 ng total RNA, with the average purity of 1.9 (A 260/280) respectively. The total concentration obtained was sufficient for the transcriptome and other downstream assays. Conclusion: We have documented important steps and factors to consider in identifying the relevant participants and required laboratory sample processes prior to the final stage, which involves total reticulocyte RNA sequencing.

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A rare disease is generally defined as a condition which affects about 1 among 2000 people and currently, there are approximately 5000-8000 rare diseases (RDs) affecting over 400 million people world-wide. Although RDs may arise from different causes such as infections and environmental factors, about 80% are caused by genetic abnormalities. In Tanzania, there are no reports of the types of RDs, their incidence, distribution and numbers of individuals affected. In addition, there have been no strategies to map RDs in the country and develop a definition that fits the local context. Public awareness and understanding of RDs are very limited, and these lead to poor management and stigmatisation of patients. To address the ongoing problems, Tanzania joined other countries world-wide and global partners to commemorate the rare diseases day (RDD) for the first time in 2016 and subsequently every year. Unlike previous years where the RDD was organised by Ali Kimara Rare Diseases Foundation (AKRDF) with few partners, in 2020, a bigger event was co-hosted by Ali AKRDF and Tanzania Human Genetics Organization together with government representatives and other multiple partners. The organisers, government representatives and participants proposed a national "Call for Action" with the overall goal of improving the lives of patients/individuals with RDs. The call focuses and aims to address 17 strategic issues that are broadly categorised into four areas. These include generating demographic data of individuals with RDs; advocating for policies and guidelines for diagnosis, care, treatment and health financing; developing policies supporting public education, awareness and advocacy; and strengthening research, innovation and public-private partnerships. If adopted and implemented, the potential impacts of these recommendations will include improved access to adequate and high-quality health and education services, and policies and guidelines to address the current and future challenges facing individuals with RDs and their families.

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BACKGROUND: Sickle cell disease (SCD) is an important cause of <5 mortality. In Tanzania, it is estimated up to 11 000 children are born with SCD annually, making this the fifth country with the highest SCD annual births worldwide. The biggest challenge of expanding the service of newborn screening for SCD as the national health intervention in Tanzania is due to the high cost of the currently used assays and lack of rapid screening methods. Therefore, in this study, we assessed the diagnostic accuracy of point-of-care tests for SCD diagnosis in newborns. AIM: To evaluate the sensitivity and specificity of HemotypeSC™ and sickle SCAN® in diagnosing SCD in newborns. METHODS: Diagnostic accuracy of HemotypeSC™ and sickle SCAN® were evaluated in comparison to isoelectric focusing as a confirmatory method. RESULTS: A total of 706 newborns were enrolled in the study. The sensitivity and specificity of HemotypeSC in detecting Hb SS, Hb AS and Hb AA phonotypes was 100%. The sensitivity and specificity of sickle SCAN® in detecting Hb SS, Hb AS and Hb AA phenotypes were 100%, 97% and 100% respectively. CONCLUSION: Both POC tests displayed high accuracy in detecting SCD, we believe the introduction of either of these tests in health facilities will help in the early detection and management of SCD. In addition, the margin of cost per test is relatively affordable (1.4$ per test for HemotypeSC™ and 4.75$ for sickle SCAN®).

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Human genetics research and applications are rapidly growing areas in health innovations and services. African populations are reported to be highly diverse and carry the greatest number of variants per genome. Exploring these variants is key to realize the genomic medicine initiative. However, African populations are grossly underrepresented in various genomic databases, which has alerted scientists to address this issue with urgency. In Tanzania, human genetics research and services are conducted in different institutions on both communicable and noncommunicable diseases. However, there is poor coordination of the research activities, often leading to limited application of the research findings and poor utilization of available resources. In addition, contributions from Tanzanian human genetics research and services are not fully communicated to the government, national, and international communities. To address this scientific gap, the Tanzania Society of Human Genetics (TSHG) has been formed to bring together all stakeholders of human genetics activities in Tanzania and to formally bring Tanzania as a member to the African Society of Human Genetics. This article describes the inauguration event of the TSHG, which took place in November 2019. It provides a justification for its establishment and discusses presentations from invited speakers who took part in the inauguration of the TSHG.

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