Genomic Analysis of Schizophrenia in Consanguineous Palestinian Families

描述（由申请人提供）：这个FIRCA的目标是在巴勒斯坦近亲家庭中识别负责精神分裂症的基因。该项目的基本原理是，精神分裂症可能是由参与神经发育的基因中罕见的严重突变引起的，而患有精神分裂症的近亲，严重受影响的家庭可能携带这种隐性等位基因突变。FIRCA的父母资助是“精神分裂症的基因组方法”（1 R01 MH083989）。FIRCA的巴勒斯坦PI是伯利恒大学生物科学助理教授Hashem Shahin博士。作为与King实验室在巴勒斯坦家族遗传性听力损失基因组分析方面10年合作的结果，Shahin博士在使用纯合子作图、CNV分析以及最近的下一代测序进行基因发现方面经验丰富。这次FIRCA是Shahin博士第一次申请研究经费。FIRCA项目有三个目标。目的1。沙欣博士将与伯利恒精神病院院长Issam Bannoura博士一起，确定并登记患有严重精神分裂症的家庭。目标2。在伯利恒大学，沙欣博士将使用Affymetrix平台进行纯合子映射和纯合子拷贝数变异分析。在华盛顿大学的King实验室，他将对纯合性扫描确定的连接区域进行下一代测序，并使用定制阵列捕获。目标3。同样在伯利恒大学，沙欣博士将验证和描述候选突变。每一步，新技术都将被转移到伯利恒。FIRCA的支持将使约15个多路家庭得以评估。如果这种基于纯合子定位的基因发现方法揭示了精神分裂症的新基因，FIRCA的结果将用于提出更广泛的项目。

DESCRIPTION (provided by applicant): The goal of this FIRCA is to identify genes responsible for schizophrenia in consanguineous Palestinian families. The rationale for the project is that schizophrenia may be caused by rare severe mutations in genes involved in neurodevelopment, and that individuals with schizophrenia in consanguineous, severely affected families may harbor such mutations as recessive alleles. The parent grant of the FIRCA is "A Genomic Approach to Schizophrenia" (1 R01 MH083989). The Palestinian PI of the FIRCA is Hashem Shahin, PhD, Assistant Professor of Biological Sciences at Bethlehem University. As the result of ten years collaboration with the King lab on genomic analysis of inherited hearing loss in Palestinian families, Dr Shahin is experienced with gene discovery using homozygosity mapping, CNV analysis, and, most recently, next generation sequencing. This FIRCA is Dr Shahin's first application for a research grant. The FIRCA project has three aims. Aim 1. With Dr Issam Bannoura, Director of the Bethlehem Mental Hospital, Dr. Shahin will ascertain and enroll families severely affected with schizophrenia. Aim 2. At Bethlehem University, Dr. Shahin will carry out homozygosity mapping and analysis of homozygous copy number variants, both using the Affymetrix platform. In the King lab at University of Washington, he will carry out next generation sequencing of linked regions identified by the homozygosity scans and captured using custom arrays. Aim 3. Again at Bethlehem University, Dr. Shahin will validate and characterize candidate mutations. At each step, new technology will be transferred to Bethlehem. FIRCA support will enable ~15 multiplex families to be evaluated. If this homozygosity mapping-based approach to gene discovery reveals new genes for schizophrenia, FIRCA results will be used to propose a project of wider scope. PUBLIC HEALTH RELEVANCE: The goal of this proposal for a Fogarty International Research Collaboration Award (FIRCA) is to identify genes responsible for schizophrenia in consanguineous Palestinian families. The rationale for the project is that schizophrenia may be caused by rare severe mutations in genes involved in neurodevelopment, and that individuals with schizophrenia in consanguineous, severely affected families may harbor such mutations as recessive alleles. If this project reveals new genes for schizophrenia, the results will be used to propose a project of wider scope.