Case Studies In Genetics

遗传学案例研究

• 批准号: 9160917
• 负责人: Alejandro A Schaffer
• 金额: $ 32.72万
• 依托单位: NATIONAL LIBRARY OF MEDICINE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9160917
• 关键词: Affect; Bioinformatics; Biological; CSF3 gene; Cancer Model; Carcinoid Tumor; Case Study; Chromosomes; Clinical; Collaborations; Computer software; Data; Databases; Disease; Filgrastim; First Degree Relative; Gastroenterology; Gene Dosage; Genealogy; Genes; Genetic; Genetic study; Genome; Germany; Goals; Human; Individual; Inherited; Intervention; Maps; Methods; Modeling; Molecular; Mutation; National Human Genome Research Institute; National Institute of Diabetes and Digestive and Kidney Diseases; Nature; Neutropenia; Operative Surgical Procedures; Patients; Predisposition; Publications; Publishing; Recombinants; Research Personnel; Scientist; Software Tools; United States National Institutes of Health; Universities; Work; cancer genetics; career; meetings; precision medicine; screening; standard care

During my career I have worked on several projects creating software (FASTLINK, CASPAR, rh_tsp_map, PedHunter, etc.) and a database (Anabaptist Genealogy database) for genetic studies. My association with this software and a past track record of effective collaboration with wet lab scientists leads to more such collaborations. Three highlights from my publications of the past year are: -- characterization of a previously unrecognized form of severe congenital neutropenia (SCN), due to mutations in JAGN1. This is a clinically important example of precision medicine because recombinant human G-CSF (a.k.a. filgrastim, neupogen) is a standard treatment for neutropenia patients, but these patients with biallelic mutations in JAGN1 do not respond to this treatment. This finding was published in Nature Genetics. -- molecular characterization of the first hereditary form of susceptibility to carcinoid tumors, due to a mutation in IPMK. This is clinically important because it provides the strongest proof to date that carcinoid tumors can be familial and therefore first-degree relatives of affected individuals should be screened. The clinical/surgical part of the study showed that early screening and surgery is curative. This work was published in Gastroenterology. -- completion of a new version of the cancer genetics software FISHtrees including new methods to model simultaneously single-gene copy number changes, single chromosome copy-number changes, and genome duplications. This work was selected for presentation at the highly selective (< 20% acceptance rate) ISMB 2015 meeting and published in the associated issue of Bioinformatics. The work on JAGN1 mutations was done in collaboration with the group of Christoph Klein (Munich, Germany). The work on the IPMK mutation was done in collaboration with the groups of Stephen Wank (NIDDK/NIH) and Joan Bailey-Wilson (NHGRI/NIH) The work on the FISHtrees software was done in collaboration with the groups of Russell Schwartz (Carnegie Mellon University) and Thomas Ried (NCI/NIH).

在我的职业生涯中，我从事多个项目（FastLink，caspar，rh_tsp_map，pedhunter等）和一个数据库（Anabaptist家谱数据库）进行遗传研究。 我与该软件的关联以及有效协作的过去记录 凭借湿实验室的科学家，可以进行更多此类合作。 我过去一年的出版物的三个亮点是： - 表征先前未知的严重形式 由于JAGN1突变，先天性中性粒细胞减少症（SCN）。 这是临床上重要的精确例子 医学是因为重组人G-CSF（又名Filgrastim，Neupogen）是 中性粒细胞减少患者的标准治疗方法，但这些患者 JAGN1中的双重突变不反应 这种处理。这一发现发表在自然遗传学中。 - 第一种遗传形式的分子表征 由于突变中的类癌肿瘤的敏感性 IPMK。这在临床上很重要，因为它提供了 迄今为止最有力的证据表明类癌肿瘤可以 是家族性的，因此是一级亲戚 应筛选受影响的人。临床/手术 研究的一部分表明，早期筛查和手术是 治愈性。这项工作发表在胃肠病学上。 - 完成新版本的癌症遗传学软件 钓树包括同时建模的新方法 单基因拷贝数更改，单染色体拷贝数 变化和基因组重复。选择了这项工作 以高度选择性的介绍（<20％的接受率） ISMB 2015会议，并在相关问题上发表 生物信息学。 JAGN1突变的工作是与 克里斯托夫·克莱因（Christoph Klein）（德国慕尼黑）。 IPMK突变的工作是与小组合作完成的 Stephen Wank（Niddk/NIH）和Joan Bailey-Wilson（NHGRI/NIH） Fishtrees软件上的工作是与 罗素·施瓦茨（Carnegie Mellon University）和Thomas Ried团体 （NCI/NIH）。