International Registry of Werner Syndrome

维尔纳综合征国际登记处

基本信息

批准号：
8339584
负责人：
GEORGE M. MARTIN
金额：
$ 20万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-08-15 至 2015-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8339584
关键词：
Adult Affect Aging Alleles Appearance Area Atherosclerosis Bilateral Biochemical Genetics Biocompatible Materials Biological Biological Aging Blood specimen Boston Cancer Center Cataract Centenarian Clinical Clinical Data Code Collaborations Communities Complementary DNA Cultured Cells DNA Damage Development Diagnosis Disease Enhancers Epidemiologic Studies Epithelial Exonuclease Eye Development Family Family member Fibroblasts Funding General Population Genes Genetic Genetic Research Genome Genome Stability Genotype Germany Goals Human International Investigation Japan Japanese Population Longevity Maintenance Malignant Neoplasms Medicine Methodology Molecular Diagnosis Mutation Non-Insulin-Dependent Diabetes Mellitus Nonsense-Mediated Decay Octogenarian Osteoporosis Parents Pathway interactions Patients Phenotype Plasma Reagent Recruitment Activity Registries Research Research Institute Research Personnel Resistance Resources Sampling Siblings Skin Speed Stem cells Structure Surveys Syndrome Tissue Sample Universities WRN gene Washington Werner Syndrome Work age related aged base biological research college established cell line exome genetic linkage analysis genetic pedigree helicase human WRN protein interest lens lymphoblastoid cell line middle age novel null mutation peripheral blood senescence

项目摘要

Werner syndrome (WS) is the prototypic segmental progeroid syndrome. Started in 1988, the International Registry of Werner Syndrome has served as a resource to ascertain and genotype WS pedigrees, establish and cryopreserve biological materials from these pedigrees and provide these materials to investigators around the world. We also provide public information about WS to clinicians and to the general public. This network of resources led to the discovery of the WRN gene responsible for classical WS as well as novel LMNA mutations among patients with atypical Werner syndrome (AWS). As requested by the Japanese Werner Consortium (P.I. Koutaro Yokote, Chiba University, Japan), we assist in their nation-wide survey of WS and in collaborative epidemiological studies to evaluate the phenotypes of heterozygous carriers of WRN mutations (Keitaro Matsuo, Aichi Cancer Center Research Institute, Japan). The Registry has evolved to accept cases with a broader range of progeroid phenotypes in order to facilitate the discovery of new biochemical genetic pathways with the potential to modulate mechanisms of intrinsic biological aging. Examples include HapMap linkage analysis (P.I. Christian Kubisch, University of Ulm, Germany) and whole exome sequencing (P.I. Deborah Nickerson, University of Washington). We now propose to expand the scope of our Werner Registry to seek evidence for alleles at WRN and other loci that are associated with unusually enhanced functions. We will bring together two heretofore rather separate gerontologic communities: our colleagues who focus on deleterious mutations associated with progeroid syndromes and those interested in the genetic basis of unusually successful aging (Thomas Perls, Boston University, Nir Barzilai, Albert Einstein College of Medicine). The initial focus is to elucidate the functional significance of WRN SNPs in coding areas and putative cis-regulatory domains associated with exceptional longevity (Akira Yasui, Tohoku University, Japan; Lawrence A. Loeb, University of Washington). These studies will be extended to other relevant loci, including LMNA and newly identified AWS genes.

沃纳综合征 (WS) 是典型的节段性早衰综合征。维尔纳综合症国际登记处始于 1988 年，一直是确定 WS 谱系并对其进行基因分型、建立和冷冻保存这些谱系的生物材料并将这些材料提供给世界各地的研究人员的资源。我们还向临床医生和公众提供有关 WS 的公共信息。这个资源网络导致发现了导致经典 WS 的 WRN 基因以及非典型维尔纳综合征 (AWS) 患者中的新型 LMNA 突变。应日本 Werner 联盟（P.I. Koutaro Yokote，日本千叶大学）的要求，我们协助他们进行全国范围的 WS 调查和合作流行病学研究，以评估 WRN 突变杂合子携带者的表型（Keitaro Matsuo，爱知县癌症中心）日本研究所）。该登记处已发展到接受具有更广泛早衰表型的病例，以促进发现具有调节内在生物衰老机制潜力的新生化遗传途径。例子包括 HapMap 连锁分析（P.I. Christian Kubisch，德国乌尔姆大学）和全外显子组测序（P.I. Deborah Nickerson，华盛顿大学）。我们现在建议扩大 Werner 登记范围，以寻找 WRN 和其他与异常增强功能相关的基因座等位基因的证据。我们将汇集两个迄今为止相当独立的老年学社区：我们的同事专注于与早衰综合症相关的有害突变，而那些对异常成功衰老的遗传基础感兴趣的同事（托马斯·佩尔斯，波士顿大学，尼尔·巴齐莱，阿尔伯特·爱因斯坦医学院）。最初的重点是阐明 WRN SNP 在编码区和与超长寿命相关的推定顺式调控域中的功能意义（Akira Yasui，日本东北大学；Lawrence A. Loeb，华盛顿大学）。这些研究将扩展到其他相关基因座，包括 LMNA 和新发现的 AWS 基因。