Molecular Genetic Etiology of Craniosynostosis among Ghanaians (MoGECaG)

加纳人颅缝早闭的分子遗传学病因学 (MoGECaG)

• 批准号: 10238146
• 负责人: MICHAEL L CUNNINGHAM
• 金额: $ 16.26万
• 依托单位: KWAME NKRUMAH UNIVERSITY/SCIENCE/TECH
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-01 至 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10238146
• 关键词: 12 year old; Affect; Africa; Africa South of the Sahara; African; Applications Grants; Basic Science; Bioinformatics; Bone Tissue; Calvaria; Caring; Cell Line; Cephalic; Child; Clinic; Clinical; Cluster Analysis; Collaborations; Computer software; Congenital Abnormality; Country; Coupled; Craniosynostosis; DNA; Data; Defect; Environmental Risk Factor; Esthetics; Etiology; Family; Financial Hardship; Functional disorder; Future; Genes; Genetic Counseling; Genetic Predisposition to Disease; Genetic Research; Genetic Risk; Genetic Variation; Genetic study; Genome; Ghana; Goals; Growth; Haplotypes; Human; Individual; Infrastructure; Institution; Intracranial Hypertension; Iowa; Joint structure of suture of skull; Knowledge; Life; Live Birth; Metabolic Pathway; Molecular Genetics; Mutation; Neonatal Screening; Ontology; Operative Surgical Procedures; Oral; Osteoblasts; Parents; Patients; Play; Politics; Polymerase Chain Reaction; Population; Principal Investigator; Process; RNA; RNA analysis; Research; Research Infrastructure; Research Institute; Research Personnel; Research Project Grants; Reverse Transcription; Role; Saliva; Sampling; Science; Surgeon; Susceptibility Gene; Syndrome; Technology; Tissue Culture Techniques; Tissue-Specific Gene Expression; Tissues; Training; Trauma; Universities; Variant; Visit; Washington; arm; bone; case control; craniofacial; cranium; differential expression; established cell line; exome; exome sequencing; feasibility research; gene discovery; genetic testing; genetic variant; high risk; low and middle-income countries; maxillofacial; multidisciplinary; next generation; orofacial cleft; premature; psychosocial; recruit; saliva sample; skills; skull abnormality; transcriptome sequencing

Craniosynostosis is the second most common craniofacial birth defect after orofacial clefts (OFCs) affecting 1 in 2000 to 2,500 live births. The condition has a multifactorial etiology, with both genetic and environmental risk factors playing crucial roles. Approximately 90% of craniosynostosis cases are non-familial and about 15% of cases are syndromic, presenting with other extra-cranial anomalies in about 180 syndromes. The defect emanates from premature fusion of one or more cranial sutures culminating in abnormal skull growth and increased intracranial pressure. Just like other craniofacial birth defects, craniosynostosis has life-long psychosocial, esthetic, clinical and financial burden on affected individuals and families. As is common with many genetic studies, sub-Saharan African is conspicuously missing in genetic etiologic studies aimed at elucidating the pathophysiology of craniosynostosis. This notwithstanding, the vast genetic diversity of the sub- Saharan African genome, coupled with its shorter haplotype block offer a great potential for etiologic variant and/or gene discovery for craniosynostosis. To the best of our knowledge, we are proposing the first ever genetic research project on craniosynostosis among sub-Saharan Africans. The specific aims of this collaborative research project are threefold: (a) to build research capacity in craniosynostosis in Ghana, with a long term goal to extend to other African countries, (b) to carry out differential gene expression between nonsyndromic craniosynostosis cases and controls, and (c) to carry out whole exome sequencing of syndromic and nonsyndromic craniosynostosis cases. Specific aim 1 will hone the knowledge and skill of the Ghanaian team in craniosynostosis research whereas specific aims 2 and 3, inter alia, will build research infrastructure in Ghana. These are necessary for the Ghanaian team to transition into independent investigators in craniosynostosis research in the future. These specific aims will be achieved through the collaborative efforts of three Principal Investigators: Drs. Lord Jephthah Joojo Gowans and Solomon Obiri-Yeboah of Kwame Nkrumah University of Science and Technology, Ghana, and Michael L. Cunningham of Seattle Children’s Craniofacial Center and the University of Washington, USA. Dr. Peter Donkor, an Oral and Maxillofacial Surgeon, educator and researcher, will serves as the consultant on the project. The proposed project has the potential of revealing population-specific genetic variants and/or genes that may predispose individuals to craniosynostosis. The project also has translational potential as it will identify high risk families – a necessity for genetic counselling. This is particularly important in a Lower and Middle Income Country like Ghana, where genetic tests and newborn screening is almost non-existent.

颅缝早闭是第二个最常见的颅面出生缺陷后，口面裂（OFCs） 影响到2000至2，500名活产婴儿中的1人。这种情况有一个多因素的病因，既遗传 环境风险因素起着关键作用。大约90%的颅缝早闭病例 是非家族性的，约15%的病例是综合征，表现为其他颅外 约180种综合征的异常。缺陷源于一个或多个 颅缝导致颅骨异常生长和颅内压升高。就像 其他颅面出生缺陷，颅缝早闭具有终身的社会心理，美学，临床和 对受影响的个人和家庭造成经济负担。正如许多遗传学研究所常见的那样， 撒哈拉以南非洲人在遗传病因学研究中明显缺失，旨在阐明 颅缝早闭的病理生理学尽管如此，亚- 撒哈拉非洲基因组，加上其较短的单倍型块提供了一个巨大的潜力， 病因变异和/或基因发现。据我们所知， 提出了第一个关于撒哈拉以南非洲人颅缝早闭症的基因研究项目。 这一合作研究项目的具体目标有三个：（a）建立研究能力 在加纳的颅缝早闭症中，长期目标是扩展到其他非洲国家，（B）携带 在非综合征性颅缝早闭症病例和对照之间的差异基因表达， (c)对综合征型和非综合征型颅缝早闭病例进行全外显子测序。 具体目标1将磨练加纳团队在颅缝早闭方面的知识和技能 具体目标2和3除其他外将在加纳建立研究基础设施。 这些是加纳小组过渡到独立调查员所必需的。 颅缝早闭症的研究。这些具体目标将通过 三位主要研究者的合作努力：Drs. Lord Jephthah Joojo Gowans和 加纳Kwame Nkrumah科技大学的所罗门奥比里-耶博阿， Michael L.坎宁安的西雅图儿童颅面中心和大学 美国华盛顿。Peter Donkor博士，口腔颌面外科医生，教育家和研究员， 威尔是这个项目的顾问。该项目有可能揭示 群体特异性遗传变异和/或可能使个体易患 颅缝早闭该项目还具有转化潜力，因为它将确定高风险家庭- 遗传咨询的必要性这在中低收入国家尤为重要。 像加纳这样的国家，基因检测和新生儿筛查几乎不存在。