DIVERGENT MEIOTIC RECOMBINATION IN BIPOLAR DISORDER

双相情感障碍中不同的减数分裂重组

基本信息

批准号：
8797263
负责人：
Art Petronis
金额：
$ 24.64万
依托单位：
CENTRE FOR ADDICTION AND MENTAL HEALTH
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-09-26 至 2018-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8797263
关键词：
Accounting Address Affect Agreement Algorithms Attention Biology Biomedical Research Bipolar Disorder Brain Diseases Cells Chromosome Mapping Chromosomes Complex DNA DNA Markers Data Detection Development Diabetes Mellitus Disease Distant Epigenetic Process Event Family Generations Genes Genetic Genetic Markers Genetic Recombination Genome Germ Cells Goals Haploidy Haplotypes Hereditary Disease Heritability Human Huntington Disease Individual Inherited Investigation Life Linkage Disequilibrium Maps Measurement Meiosis Meiotic Recombination Mental disorders Methodology Modification Molecular Molecular Genetics Myotonic Dystrophy Organism Pathologic Processes Patients Pattern Population Psychotic Disorders Recording of previous events Reporter Research Research Personnel Rest Risk Risk Factors Science Somatic Cell Test Result Testing Therapeutic Tissues Uncertainty Variant base case control cost disorder risk epigenome genetic pedigree genetic risk factor genome sequencing genome-wide human disease innovation insight interest male malignant breast neoplasm men novel novel diagnostics offspring prognostic public health relevance sperm cell success transmission process

项目摘要

DESCRIPTION (provided by applicant): The ultimate goal of biomedical research is to identify the underlying causes of human disease. Traditional approaches for identify disease-associated genes either track multiple DNA markers through large disease-affected family pedigrees, or perform large-scale genome-wide searches for loci that are differentiated between cases and controls. Despite the success of these approaches for simple disorders, identification of genetic risk factors in complex non-Mendelian diseases such as bipolar disorder remains challenging. We examined old genetics studies of human diseases and serendipitously noticed that genetic recombination appears to occur at different rates between cases and controls in the regions containing disease genes; this effect was seen in simple genetic diseases such as Huntington's disease and myotonic dystrophy, as well as in several complex diseases such as major psychosis, breast cancer, and diabetes. If real, such an effect would point to unknown biology associated with disease. Following this observation, we have developed a strategy for the systematic investigation of this phenomenon. Our hypothesis is that recombination shows localized difference at disease-associated loci in affected individuals compared to controls. As such, the main goal of this project is to map large numbers of the recombination events occurring in males affected with bipolar disorder via high throughput single cell sequencing of sperm, and compare this to the maps from unaffected subjects. The project may uncover indicators of diseases that have previously been overlooked, and therefore provide new insight into disease biology.

描述（由适用提供）：生物医学研究的最终目标是确定人类疾病的根本原因。传统的方法，用于通过大型疾病影响的家族谱系来鉴定与疾病相关的基因跟踪多个DNA标记，或者对全基因组进行大规模的大规模基因组搜索，这些搜索在病例和对照组之间有区别。尽管这些方法成功地用于简单疾病，但鉴定出复杂的非蒙德氏疾病（例如双相情感障碍）中遗传危险因素仍然受到挑战。我们检查了对人类疾病的旧遗传学研究，并偶然发现，遗传重组似乎以不同的病例和对照组的速率发生在含有疾病基因的区域的情况下。在简单的遗传疾病（例如亨廷顿氏病和肌营养不良症）以及多种复杂疾病（例如重大精神病，乳腺癌和糖尿病）中可以看出这种作用。如果真实，这种影响将指出与疾病相关的未知生物学。在观察之后，我们制定了一种对该现象进行系统投资的策略。我们的假设是，与对照组相比，重组在受影响的个体中显示出与疾病相关的地方的局部差异。因此，该项目的主要目标是绘制通过精子的高吞吐量单细胞测序受到双相情感障碍的男性发生的大量重组事件，并将其与未受影响的受试者的地图进行比较。该项目可能会发现以前被忽视的疾病的指标，因此为疾病生物学提供了新的见解。