IDENTIFICATION OF GENES PREDISPOSING TO PELVIC FLOOR DISORDERS

盆底疾病易感基因的鉴定

• 批准号: 8486463
• 负责人: Lisa Cannon Albright
• 金额: $ 64.49万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-15 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8486463
• 关键词: Affect; Age; BRCA1 gene; BRCA2 gene; Candidate Disease Gene; Chromosome Arm; Chromosome Mapping; Chromosomes, Human, Pair 1; Chromosomes, Human, Pair 9; Clinical; Code; Collaborations; Complex; Computer software; Computerized Medical Record; DNA; Data; Data Analyses; Databases; Development; Diagnosis; Disease; Frequencies; Funding; Genealogy; Genes; Genetic; Genetic Heterogeneity; Genotype; Health; Healthcare Systems; Hospitals; Inbreeding; Individual; Intervention; Link; Malignant Neoplasms; Medical; Medical Record Linkage; Methodology; Methods; Mutation; Operative Surgical Procedures; Organ; Patients; Pelvic Floor Disorders; Pelvis; Population; Population Database; Predisposition; Prevention; Procedures; Ptosis; Public Health; Recruitment Activity; Recurrence; Research; Research Personnel; Resources; Risk; Risk Factors; SNP genotyping; Sampling; Scientist; Shipping; Ships; Specificity; Staging; Susceptibility Gene; System; United States National Institutes of Health; Utah; Variant; Woman; abstracting; case control; computerized; density; experience; genetic analysis; genetic linkage analysis; genetic pedigree; genetic resource; genome wide association study; genome-wide; genome-wide analysis; genome-wide linkage; high risk; interest; novel strategies; population based; screening; sex; success

Abstract The investigators propose a unique and powerful collaboration between basic and clinical scientists in Utah to identify genes affecting predisposition to pelvic organ prolapse (POP). The co-PIs both have significant experience, Dr. Norton in Pelvic Floor Disorder (PFD) genetics and Dr. Cannon-Albright in predisposition gene identification. The investigators will access the Utah Population Database, a computerized genealogy of Utah combined with decades of medical data from the two largest healthcare systems in Utah (serving 90% of the state), to identify and recruit surgically treated cases of POP (1,250 cases in 5 years). All POP cases sampled will be genotyped with the Illumina 610Q SNP marker set. The PIs will apply multiple different genetic analyses to this resource of genotyped POP cases to aid in the identification of predisposition genes. The record linkage of medical procedure codes (identifying surgeries performed on each patient) to individual genealogy data allows us to identify all genetic relationships among the POP cases. We will perform genome-wide association analysis, using software we have developed which allows inclusion of both independent and related cases. We will identify all genetic relationships between the sampled POP cases and perform linkage analysis in informative, high-risk POP pedigrees. We will identify chromosomal regions shared Identical by Descent (IBD) in very distantly related cases in these pedigrees, and we will identify IBD sharing within the small subset of POP cases (2%) who are inbred. Initial collaborative analysis of data obtained by Dr. Norton's NIH funded study of affected PFD sib-ships has already provided significant evidence for a predisposition gene localization on chromosome arm 9q, and suggestive evidence for at least one other locus on chromosome 1. In summary, we will create a population-based resource of surgically treated POP cases, we will pursue established and new methods to identify and localize predisposition genes affecting POP, and we will begin a detailed search for the chromosome 9 gene we have localized.

摘要 研究人员建议在犹他州的基础和临床科学家之间进行独特而有力的合作 目的确定影响盆腔器官脱垂(POP)易感性的基因。共同采购经理人都有显著的 经验，诺顿博士研究盆底疾病(PFD)遗传学，坎农-奥尔布赖特博士研究易感性 基因鉴定。调查人员将访问犹他州人口数据库，这是一个计算机化的家谱 结合来自犹他州两个最大的医疗保健系统的数十年医疗数据(服务 90%的州)，以确定和招募经手术治疗的持久性有机污染物病例(5年内1,250例)。全是流行音乐 样本病例将使用Illumina 610Q SNP标记集进行基因分型。PI将应用多个 对这一基因分型的流行病例来源进行不同的基因分析以帮助鉴定 易感基因。医疗程序代码的记录链接(识别在 每个患者)到个人家谱数据，使我们能够识别POP之间的所有遗传关系 案子。我们将使用我们开发的软件进行全基因组关联分析，该软件允许 包括独立案件和相关案件。我们将确定所有的遗传关系之间的关系 抽样流行病例，并在信息量大、风险高的流行家系中进行连锁分析。我们将确定 在这些家系中，在非常遥远的亲缘关系的病例中，通过下降(IBD)共享相同的染色体区域， 我们将确定在近亲繁殖的POP病例的一小部分(2%)中共享IBD。首字母 对诺顿博士资助的受影响的PFD同胞研究获得的数据进行协作分析 已经为易感基因在染色体9q上的定位提供了重要证据，并且 至少在1号染色体上还有一个其他基因座的提示性证据。总而言之，我们将创建一个 以人口为本的外科治疗的POP病例资源，我们将寻求既有的和新的方法来 识别和定位影响持久性有机污染物的易感基因，我们将开始详细寻找 我们已经定位了9号染色体基因。

项目成果

Identification of six loci associated with pelvic organ prolapse using genome-wide association analysis.

• DOI: 10.1097/aog.0b013e318236f4b5
• 发表时间: 2011-12
• 期刊: Obstetrics and gynecology
• 影响因子: 7.2
• 作者: Allen-Brady K;Cannon-Albright L;Farnham JM;Teerlink C;Vierhout ME;van Kempen LCL;Kluivers KB;Norton PA
• 通讯作者: Norton PA

Molecular Landscape of Pelvic Organ Prolapse Provides Insights into Disease Etiology.

• DOI: 10.3390/ijms24076087
• 发表时间: 2023-03-23
• 期刊: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
• 影响因子: 5.6
• 作者: Kluivers, Kirsten B.;Lince, Sabrina L.;Ruiz-Zapata, Alejandra M.;Post, Wilke M.;Cartwright, Rufus;Kerkhof, Manon H.;Widomska, Joanna;De Witte, Ward;Pecanka, Jakub;Kiemeney, Lambertus A.;Vermeulen, Sita H.;Goeman, Jelle J.;Allen-Brady, Kristina;Oosterwijk, Egbert;Poelmans, Geert
• 通讯作者: Poelmans, Geert

The familiality of pelvic organ prolapse in the Utah Population Database.

犹他州人口数据库中盆腔器官脱垂的家族性。

• DOI: 10.1007/s00192-012-1866-0
• 发表时间: 2013
• 期刊: International urogynecology journal
• 影响因子: 1.8
• 作者: Norton,PeggyA;Allen-Brady,Kristina;Cannon-Albright,LisaA
• 通讯作者: Cannon-Albright,LisaA