Case Studies In Genetics

遗传学案例研究

• 批准号: 6988469
• 负责人: Alejandro A Schaffer
• 金额: --
• 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/6988469
• 关键词: Mennonite; Parkinson' s disease; animal genetic material tag; animal population genetics; autosomal recessive trait; biotechnology; case history; cats; clinical research; comparative genomic hybridization; congenital oral /facial /cranial defect; family genetics; genetic disorder; genetic susceptibility; glaucoma; human genetic material tag; human population genetics; human subject; immunoglobulin E; linkage mapping; melanoma; micrencephaly; microarray technology; neoplasm /cancer classification /staging; neoplasm /cancer genetics; neutropenia

Dr. Agarwala and I continue collaborations with L. Biesecker (NHGRI) and the group of A.Shuldiner and B. Mitchell (U. Maryland Medical School) in development and usages of the Anabaptist Genealogy Database (AGDB), a large computer-searchable genealogy of North American Anabaptists, which was constructed in previous years. The main advance during the past year was that Dr. Agarwala, summer student Joshua Rosenthal, and I enlarged the database from over 295,000 individuals (version 3, finished in 2000) to over 417,000 individuals (now called AGDB, version 4). We also added several new queries and other features to our PedHunter software that is used by us to search AGDB and by other groups to search their own genealogy databases. Drs. Agarwala, Biesecker and I continued a collaboration with D. Marchuk (Duke University) hunting for one or more genes associated with venous malformations in the Amish. During this past year the collaboration with Drs. Shuldiner and Mitchell yielded one manuscript on incidence of hip fractures and osteoporosis published in Journal of Bone and Mineral Research. I continue to collaborate with Dr. B. Grimbacher (U. Freiburg) and Dr. J. Puck (NHGRI) to hunt genes for hyperIgE syndrome, common variable immune deficiency (CVID), neutropenia, and other disorders related to the immune system. During the past 12 months: Dr. Grimbacher and I published one reviewe article on common variable immune deficiency Dr. Grimbacher identified strong evidence for a gene causing neutropenia, based on a list of candidate genes I derived last year; Dr. Grimbacher identified mutations in two new candidate genes for common variable immune deficiency, in some families we are also studying by linkage analysis; In those same families I reanalyzed previously published genotype data in a new way, and identified 3 genomic regions worthy of fine fine mapping and further analysis. Dr. Puck and I studied analyzed some genes that are good candidates to modify the severity of the ALPS phenotype. My collaboration with Dr. S. Holland (NIAID) on studies to characterize polymorphisms and haplotypes in two human genes of interest in host defense against infection yielded two published papers: one on promoter polymorphisms of the INFNGR1 gene and the other on an intronic polymorphism of the TLR2 gene. I continue to collaborate with P. Henthorn (U. Penn) and J. Fyfe (Michigan State) on a linkage study of a large canine pedigree that has multiple occurrences of three autosomal recessive traits. During the past 12 months a paper on linkage for a vitamin B12 malabsorption trait was published for publication in Mammalian Genome. We continued to hunt genes for the other two traits, but have not found linkage yet. My collaboration with Dr. Fyfe was expanded and coalesced with the cat map work described below to also include genetic studies of a cat pedigree with numerous cases of spinal muscular atrophy, not caused by disruptions of the SMN gene (which is the principal cause of spinal muscular atrophy in humans). Dr. Agarwala I continue to collaborate with M. Mennoti-Raymond(NCI) and W. J. Murphy (was at NC, moved to Texas A&M) on construction of maps for use in genetics. In the past 12 months we: published a third-generation radiation hybrid map of the cat in Cytogenetic and Genome Research, completed computation of a first radiation hybrid map of the macaque made numerous improvements to our rh_tsp_map software, which is used both by us in these projects and independently by other groups computing radiation hybrid maps. Dr. Richard Desper and I completed our collaboration with with Z. Huang and K. Yao (Guangzhou, China) on a study of comparative genomic hybridization data from nasopharygeal cancer. We revised a manuscript summarizing our findings, and it was published in Genes, Chromosomes & Cancer. Dr. Desper and I continued collaborating with Dr. Javed Khan (NICHD) on a new method of tumor classificaation from microarray data. During the past 12 months we refined the method and revised a manuscript describing the method and published it in Journal of Theoretical Biology. Dr. Desper and I collaborated with the group of Dr. Thomas Ried (NCI) on two problems in modeling aneuploidy in cancer cells. For a problem concerning modeling of possible mitotic advantage conferred by a genomic mutation, we completed both analytic work leading to closed-fom solutions as well as a simulation program. We wrote a manuscript on the mitotis modeling problem and submitted it for publication. Dr. Robert Nussbaum (NHGRI) invited me to resume our collaboration on hunting genes for Parkinson's disease, now joined by Dr. Andrew Singleton (NINDS). I had done the genetic linkage analysis computations for the first two Parkinson's disease loci in 1996. During the past year, I analyzed genome scan genotype data for two new large Parkinson's pedigrees. One pedigree shows dominant inheritance, and the other pedigree probably has recessive inheritance. In each case, we have identified at least one genomic region that looks very promising, and fine mapping of those regions is underway.

我和Agarwala博士继续与L. Biesecker（NHGRI）合作 以及A.Shuldiner和B. Mitchell（美国马里兰州医学院）的小组 洗礼家谱数据库（AGDB）的开发和用法，这是一种大型的北美洗礼式的可计算机研究的家谱 昔年。过去一年的主要进步是 Agarwala博士，夏季学生Joshua Rosenthal，我扩大了 来自295,000多人（第3版，2000年完成）的数据库至 超过417,000个人（现在称为AGDB，版本4）。 我们还为我们的Pedhunter软件添加了一些新的查询和其他功能，我们将我们用来搜索AGDB和其他组来搜索自己的家谱数据库。 博士。 Agarwala，Biesecker和我继续与D. Marchuk合作 （杜克大学）寻找与静脉相关的一个或多个基因 阿米什人的畸形。在过去的一年中 与博士。 Shuldiner和Mitchell在髋关节发生率时产生了一个手稿 骨折和骨质疏松症发表在骨骼和 矿物研究。 我继续与B. Grimbacher博士（U. Freiburg）和J. Puck博士（NHGRI）合作 为了狩猎Hyperige综合征的基因，常见的可变免疫缺陷（CVID）， 中性粒细胞减少症和与免疫系统有关的其他疾病。 在过去的12个月中： 我和Grimbacher博士发表了一篇有关常见可变免疫缺陷的评论文章 格里姆巴赫博士确定了引起中性粒细胞减少基因的有力证据，基于 我去年得出的候选基因列表； 格林巴赫博士确定了两个新候选基因的突变 免疫缺陷，在某些家庭中，我们还通过连锁分析学习； 在那些相同的家庭中，我以新的方式重新分析了以前发布的基因型数据，并且 确定了3个值得精细映射和进一步分析的基因组区域。 我和Puck博士研究了一些分析的基因，这些基因是修改该基因 阿尔卑斯表型的严重程度。 我与S. Holland博士（NIAID）在研究方面的合作，以表征 在两个宿主感兴趣的人类基因中的多态性和单倍型 针对感染的防御产生了两篇已发表的论文：一篇关于发起人的论文 Infngr1基因的多态性，另一个是内含子的 TLR2基因的多态性。 我继续与P. Henthorn（U. Penn）和J. Fyfe合作（密歇根州 状态）在一项具有多个大型犬科的连锁研究中 出现三个常染色体隐性特征。在 过去12个月的一篇关于维生素B12连接的论文 发表不良特征出版 在哺乳动物基因组中。我们继续为其他两个特征寻找基因， 但尚未找到联系。我与Fyfe博士的合作 扩展并与下面描述的猫地图工作合并 还包括对猫血统的遗传研究 脊柱肌肉萎缩的病例，不是由 SMN基因（这是脊柱肌肉萎缩的主要原因 在人类中）。 Agarwala博士一世继续与M. Mennoti-Raymond（NCI）和W. J. Murphy合作 （曾在NC，移至德克萨斯A＆M）在构造地图上用于遗传学。在过去的12个 我们几个月： 在细胞遗传学和基因组研究中发表了CAT的第三代辐射杂种图， 完成了猕猴的第一辐射混合图 对我们的RH_TSP_MAP软件进行了大量改进，这两者在这些项目中都使用 并独立于其他计算辐射杂种图的组。 理查德·佩斯特（Richard Desper）博士和我完成了与Z. Huang和K. Yao的合作 （中国广州）对比较基因组杂交数据的研究 鼻咽癌。我们修改了一个汇总我们发现的手稿，这是 发表在基因，染色体和癌症上。 佩尔斯和我继续与Javed Khan博士（NICHD）合作 从微阵列数据中的一种新的肿瘤分类方法。期间 在过去的12个月中，我们完善了该方法并修改了手稿 描述该方法并将其发表在理论生物学杂志上。 我和Dell博士与Thomas Ried博士（NCI）合作了两个 在癌细胞中建模非整倍性的问题。关于问题 通过基因组突变赋予的可能有丝分裂优势的建模，我们 还完成了两项分析工作，还可以实现封闭解决方案 作为模拟程序。我们在Mitotis建模上写了一个手稿 问题并提交出版。 罗伯特·努斯鲍姆（Robert Nussbaum）博士（NHGRI）邀请我恢复我们在狩猎方面的合作 帕金森氏病基因，现已由安德鲁·辛格尔顿（Andrew Singleton）博士（Ninds）加入。 我已经完成了前两个帕金森氏症的遗传连锁分析计算 1996年疾病基因座。在过去的一年中，我分析了基因组扫描基因型 两个新的大型帕金森氏菌的数据。一种血统表现出主导性继承， 另一种血统可能具有隐性继承。在每种情况下，我们 已经确定了至少一个看起来非常有前途的基因组区域，并进行了精细的映射 这些地区正在进行中。