Case Studies In Genetics

遗传学案例研究

• 批准号: 7148045
• 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/7148045
• 关键词: Parkinson' s disease; aneuploidy; animal genetic material tag; animal population genetics; autosomal recessive trait; biotechnology; cats; clinical research; comparative genomic hybridization; dogs; family genetics; gene mutation; genetic susceptibility; glaucoma; horses; human genetic material tag; human subject; immune system; immunodeficiency; immunogenetics; linkage mapping; microarray technology; neoplasm /cancer genetics; neutropenia; progressive spinal muscular atrophy; vitamin B12 deficiency

Dr. Agarwala and I continue a collaborations with the group of A.Shuldiner and B. Mitchell (U. Maryland Medical School) in development and usages of the Anabaptist Genealogy Database (AGDB) During the past year, we completed a manuscript relating lifespan to number of children and maternal age at last birth. This is submitted for publication. 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 article showing that mutations in TNFRSF13B are associated with common variable immunodeficiency. Dr. Grimbacher and I prepared two more manuscripts on linkage results for common variable immunodeficiency. Dr. Grimbacher identified mutations in two genes that cause different forms of syndromic neutropenia Dr. Puck and I studied analyzed some genes that are good candidates to modify the severity of the ALPS phenotype, and prepared two manuscripts on this topic. 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, we prepared a manuscript, subsequently published in Blood on mutations in the AMN gene occuring in two dog pedigrees with vitamin B12 malabsorption. 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. During the past year, we found genetic linkage and the causative gene. A manuscript is in preparation. Dr. Agarwala I continue to collaborate with M. Mennoti-Raymond(NCI) and W. J. Murphy (was at NCI, moved to Texas A&M) on construction of maps for use in genetics. In the past 12 months we publishd the first radiation hybrid map of rhesus macaque. My collaboration with Dr. Mennoti-Raymond also included hunting various genes of interest in cats using the previously built maps. During the past year, we: found genetic linkage and the gene for a cat form of spinal muscular atrophy, found gentic linkage for a cat form of retinal atrophy, found genetic linkage for three different coat color traits, and began builidng a denser genetic map of the cat The mapping work with Dr. Agarwala was expanded to include a collaboration with Prof. B. P. Chwodhary (Texas A &M) on building dense maps of the horse. So far, we have computed maps of for 4 sets of markers corresponding to 4 different human chromosomes. The first set of maps for the horse chromosomes corresponding to HSA19 is accepted for publication in Mammalian Genome. The second set of maps for the horse chromosomes corresponding to HSA2 is submitted for publication. Dr. Desper and I completed our collaboration 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 published a paper in Mathematical Biosciences. During the past year, I analyzed genome scan genotype data for two new large Parkinson's pedigrees in collaboration with Dr. Robert Nussbaum (NHGRI) and Dr. Andy Singleton(NIA) . One pedigree shows dominant inheritance and has mutation in lRRK2 for which we published a paper in Annals of Neurology. The other pedigree is still under investigation.

我和Agarwala博士继续与A.Shuldiner和B. Mitchell（美国马里兰州医学院）进行合作，从而开发和用途。 在过去的一年中，我们完成了与儿童数量有关的手稿 和孕产妇终于出生。这是提交出版的。 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： 我和格里姆巴赫博士发表了一篇文章，显示TNFRSF13B中的突变是 与常见的可变免疫缺陷有关。 我和格里姆巴赫博士准备了又有两个有关连锁结果的手稿 常见的可变免疫缺陷。 格林巴赫博士鉴定了两个引起不同形式的基因的突变 综合症中性粒细胞减少症 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，并在此主题上准备了两个手稿。 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，我们准备了一个手稿，随后 发表在两者中的AMN基因中的突变中发表 维生素B12吸收不良的狗血统。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。在过去的一年中，我们发现了遗传 链接和因果基因。手稿正在准备。 Agarwala博士一世继续与M. Mennoti-Raymond（NCI）和W. J. Murphy合作 （位于NCI，移至德克萨斯A＆M）用于构造遗传学的地图。在过去的12个 几个月，我们发布了恒河猕猴的第一辐射混合图。 我与Mennoti-Raymond博士的合作还包括狩猎的各种基因 使用先前建造的地图对猫的兴趣。在过去的一年中，我们： 发现遗传连锁和脊柱肌肉萎缩的CAT形式的基因， 找到了视网膜萎缩的猫形式的绅士联系， 找到了三种不同外套颜色特征的遗传联系， 和 开始建造猫的密集遗传图 与Agarwala博士的映射工作进行了扩展，包括与 B. P. Chwodhary教授（德克萨斯州A＆M）在建造马的密集地图上。迄今为止， 我们已经计算出与4种不同不同标记的4组标记的地图 人类染色体。与对应的马染色体的第一组地图 HSA19被接受在哺乳动物基因组中发表。第二组地图 与HSA2相对应的马染色体已提交出版。 我和Del. Deld博士完成了我们与Thomas Ried博士（NCI）的合作 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 发表了数学生物科学论文。 在过去的一年中，我分析了基因组扫描基因型 与罗伯特·努斯鲍姆（Robert Nussbaum）博士（NHGRI）合作的两个新大型帕金森的血统书的数据 和安迪·辛格尔顿（NIA）博士。一种谱系显示出主要的遗传，并在LRRK2中具有突变 为此，我们在神经病学史上发表了一篇论文。另一个血统是 仍在调查中。