Genetic Testing for Accurate Diabetes Differentiation in Nigeria

项目/摘要摘要 我之前的培训和与我的长期目标相关的曝光使K43成为全球新兴的 发展中国家是我实现作为一名独立研究员抱负的理想机会 非传染性疾病中的翻译基因组学领域。中国非传染性疾病领域的遗传学研究 一般情况下，但尤其是糖尿病在非洲非常稀少。然而，我很幸运地成为了唯一的 西非著名的糖尿病遗传项目，非洲美洲糖尿病研究，通过该研究， 我对基因研究感兴趣的种子就是培育出来的。最近，通过NIH D43合作 伊巴丹大学和芝加哥大学之间的研究培训计划，我被曝光了 此外，基因组学在提高糖尿病诊断精度方面取得了进展。为了 为了推进我作为独立调查员的职业生涯，我现在问一句，在诊断方面获得能力 非传染性疾病的分子基因组学及其在临床环境中的应用，可以转化为改进的诊断 糖尿病的精确度，特别是单基因糖尿病病因的检测作为测试案例。 糖尿病等非传染性疾病给非洲国家带来了毁灭性的后果 比如尼日利亚。造成这种情况的原因是很少获得基因检测，导致误诊或 一些病例，如单基因糖尿病(MD)，未诊断。因此，比例、光谱和 尼日利亚常见类型糖尿病患者中未诊断的MD模式仍不清楚。它 目前尚不清楚识别和解决医生对基因测试的相关障碍是否可以 促进尼日利亚MD的基因分型描述，作为将基因检测应用于其他疾病的原型 非传染性疾病。我这个K43应用程序的总体目标是描述基因的频率和频谱 尼日利亚的MD变种，同时我获得了诊断分子基因组学方面的培训和能力 以提高对这些疾病的诊断精度，从而使尼日利亚的伊巴丹成为 整个西非的转介中心。我的假设是，医生的相关因素构成了 在临床上应用和使用基因检测的重大障碍，从而导致未诊断或 尼日利亚糖尿病患者误诊为MD，他们可能有不同的基因型别 变种与其他种群相比。 在研究计划中，我描述了在尼日利亚背景下需要实现的三个具体目标 从临床上不应用基因检测转向用基因检测的结果来描述 以前未诊断出的疾病的基因型谱，例如尼日利亚的MD。这些知识和知识 然后，可以将获得的经验推广到其他非传染性疾病，并通过培训其他非传染性疾病患者来提高能力 并影响整个西非。首先，需要确定医生的相关障碍，通过 对在伊巴丹公共卫生机构执业的合格医生进行了调查。其次，我计划 制定和实施基因组学计划，通过以下方式在临床上诊断和分类糖尿病 为医生设计一个实用的、有背景的决策支持工具。最后，使用两步走战略 通过实用指南筛查可能的患者并对选定的患者进行DNA测序，然后我将 描述临床糖尿病患者中MD的频率、谱和基因型式。 为了在尼日利亚成功应用基因组学来提高非传染性疾病的诊断准确率，我 需要在基因组学、生物信息学以及领导技能方面进行进一步培训，以在 LMIC。我已经在这些领域确定并组建了一个指导委员会，我们共同拥有 我计划了一系列课程的培训计划，这将引导我实现这一目标。K43大奖将 使我有能力在非传染性疾病中独立进行表型-基因匹配， 并使伊巴丹成为西非其他地区的转介和培训中心。

PROJECT /SUMMARY ABSTRACT My prior training and exposures linked with my long-term goal makes this K43 Emerging Global Award for Developing Countries the ideal opportunity for me to realise my aspiration as an independent researcher in the field of translational genomics in non-communicable diseases. Genetic research in the area of NCDs in general, but particularly in diabetes is very sparse in Africa. I was however opportuned to be part of the only notable diabetes genetic project in West Africa, the Africa America Diabetes Mellitus Study, by which the seed of my interest in genetic research was cultivated. Recently, through the NIH D43 collaborative research-training programme between University of Ibadan and University of Chicago, I was exposed further to the impact of genomics advances in improving diagnostic precision of diabetes. In order to advance my career as independent investigator, I now ask whether acquisition of competency in diagnostic molecular genomics in NCDs, and its application in the clinic setting, can translate into improved diagnostic precision of diabetes, particularly detection of monogenic cause of diabetes as a test case. Non-communicable diseases (NCDs) such as diabetes have devastating consequences on African nations such as Nigeria. Contributing to this is very little access to genetic testing resulting in misdiagnosis or, in some cases like monogenic diabetes (MD), non-diagnosis. Consequently, the proportion, spectrum and pattern of undiagnosed MD among patients with commoner types of diabetes in Nigeria remain unknown. It is not known whether identifying and addressing physicians' related barriers to genetic testing could facilitate genotypic description of MD in Nigeria, as a prototype for application of genetic testing to other NCDs. My overall objective for this K43 application is to describe the frequency and spectrum of genetic variants of MD in Nigeria, while I obtain training and competency in diagnostic molecular genomics focused on NCDs, so as to improve diagnostic precision of these conditions and thereby make Ibadan, Nigeria, a referral center for the entire West Africa. My hypothesis is that physicians' related factors constitute significant barriers to application and utility of genetic testing in the clinic, with consequent undiagnosed or misdiagnosed MD among patients with diabetes in Nigerian, who are likely to have different genotypic variants compared to other population. In the research plan, I describe the three specific aims that need to be achieved in the Nigerian setting to move from non-application of genetic testing in the clinic to using the outcome of genetic testing to describe the genotypic spectrum of a previously undiagnosed condition such as MD in Nigeria. The knowledge and experience gained can then be extended to other NCDs and, through training of others, increase capacity and impact the whole of West Africa. First, there is need to identify physicians' related barriers by carrying out surveys among eligible doctors practicing in public health institutions in Ibadan. Secondly, I plan to develop and implement a genomics programme to diagnose and classify diabetes in the clinic through design of a practical, contextualised decision support tool for physicians. Lastly, using a two-step strategy of screening likely patients by a practical guideline and sequencing DNA of selected patients, I will then describe the frequency, spectrum and genotypic pattern of MD among clinic patients with diabetes. In order to be successful at application of genomics to improve diagnostic precision of NCDs in Nigeria, I need further training in genomics, bioinformatics as well as leadership skills required to build a RCE in a LMIC. I have identified and assembled a mentorship committee in these areas and together we have planned a curriculum of courses training programme that will lead me to this end. The K43 award will enable me to develop the competency to independently carry out phenotype-genotype matching in NCDs, and make Ibadan a referral and training centre for other parts of West Africa.