International Registry of Werner Syndrome

维尔纳综合征国际登记处

基本信息

批准号：
8521042
负责人：
GEORGE M. MARTIN
金额：
$ 18.9万
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 2015-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8521042
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 sequencing 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.

Werner综合征（WS）是原型节段性后代综合征。始于1988年，Werner综合征国际注册表已成为确定和基因型WS谱系，从这些谱系中建立和冷冻水果生物材料的资源，并向世界各地的研究人员提供这些材料。我们还向临床医生和公众提供有关WS的公共信息。这种资源网络导致了导致经典WS以及非典型Werner综合征患者（AWS）患者的新型LMNA突变的发现。按照日本Werner联盟（日本千叶大学的P.I. Koutaro Yokote）的要求，我们协助他们在全国范围内对WS的调查以及合作的流行病学研究，以评估WRN突变的杂合子载体的表型日本研究所）。该注册中心已经演变为接受具有更广泛的后代体表型的病例，以促进发现新的生化遗传途径，并可能调节内在生物学衰老的机制。例子包括HAPMAP链接分析（P.I. Christian Kubisch，德国乌尔姆大学）和整个外显子序（P.I. Deborah Nickerson，华盛顿大学）。现在，我们建议扩大Werner注册表的范围，以寻求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独立的老年学界：我们的同事专注于与雌新综合症相关的有害突变，以及那些对异常成功衰老的遗传基础感兴趣的人（波士顿大学，尼尔·巴尔西莱，艾伯特·艾伯特·爱因斯坦医学院）。最初的重点是阐明WRN SNP在编码区域以及与特殊寿命相关的假定顺式调节领域的功能重要性（Akira Yasui，日本Tohoku University，日本Tohoku University;华盛顿大学Lawrence A. Loeb）。这些研究将扩展到其他相关基因座，包括LMNA和新鉴定的AWS基因。