Improving Diagnosis of Congenital Genitourinary Anomalies

改善先天性泌尿生殖系统异常的诊断

基本信息

批准号：
9126564
负责人：
Dolores Jean Lamb
金额：
$ 34.04万
依托单位：
BAYLOR COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-09-15 至 2017-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9126564
关键词：
Affect Area Arts Back Benign Birth Bladder Bladder Exstrophy Candidate Disease Gene Caring Cell Line Child Childhood Chromosomal Duplication Chromosomal Rearrangement Chromosome Deletion Chromosome Structures Chromosome abnormality Chromosomes Clinical Complex Congenital Abnormality Copy Number Polymorphism Cryptorchidism Cytogenetic Analysis Defect Detection Development Developmental Delay Disorders Diagnosis Disease Early Diagnosis Epispadias Etiology Exhibits Failure Family Funding Future Gametogenesis Gene Dosage Gene Expression Generations Genes Genetic Genetic Counseling Genitourinary system Genome Genomics Goals Gonadal Dysgenesis Human Hypospadias In Vitro Intervention Intestines Investigation Karyotype Medical Medical Genetics Mental Retardation Modeling Molecular Molecular Abnormality Molecular Diagnosis Morphogenesis Neonatal Newborn Infant Operative Surgical Procedures Parents Patient Care Patients Physicians Population Pregnancy Process Recurrence Resolution Risk Estimate Role Scrotum Series Signal Pathway Structure Syndrome Techniques Technology Tissues Urethra Urologist Urology Work ambiguous genitalia base boys carcinogenesis comparative genomic hybridization gene discovery gene function homologous recombination improved in vivo male malformation microdeletion mouse model novel novel strategies penis psychologic psychosocial research study sex social urinary urologic

项目摘要

DESCRIPTION (provided by applicant): A challenge for pediatric urology is the surgical treatment of birth defects of the lower urinary and genitourinary tract in boys. While genitourinary birth defects are among the most common diagnosed, the molecular basis of these defects is lacking. This application seeks support to continue our investigations into the genomic basis of these birth defects. We used state-of-the-art technology, comparative genomic hybridization microarray (aCGH), to identify submicroscopic gains or losses on chromosomes in children with congenital genitourinary defects. This work identified chromosomal regions where unrelated patients with the same birth defect exhibited de novo structural chromosomal duplications or deletions too small to be seen on a karyotype. A clinically validated aCGH identified structural chromosome defects in about 20% of children with genitourinary birth defects-an advance that can be used today by pediatric urologists. Thus our first hypothesis is proven: we improved the diagnosis of these children with aCGH. We seek to continue to identify genetic hotspots for congenital genitourinary defects. Importantly, the work identified a number of candidate genes for both normal human genitourinary development and birth defects. Based upon the current studies, we have a number of candidate genes for human urogenital tract development remaining to be analyzed and our aCGH studies continue to be informative and to suggest new areas for investigation. Accordingly, our specific aims remain similar to our currently funded proposal. We seek to identify the genetic and genomic defects that underlie these common birth defects. We will continue to show gene specific causality, beyond simple association with a birth defect, through generation of mouse models and definition of gene function during tissue morphogenesis. The long-term goal of this study is to improve the diagnosis of congenital genitourinary defects and to define the genetic basis for the failure of this key biologic process for children with birth defects of the urogenital tract. Although most urogenital tract defects are surgically corrected in children by the pediatric urologist, we seek t understand the cause of the birth defect and to know the likelihood whether any future children will be similarly afflicted. This proposal uses novel approaches to improve both our understanding of the molecular basis and to improve our ability to diagnose these common birth defects of the lower urinary and genitourinary tracts.

描述（由申请人提供）：小儿泌尿科的挑战是男孩中尿和泌尿生殖道的先天缺陷的手术治疗。虽然生殖器出生缺陷是最常见的诊断之一，但缺乏这些缺陷的分子基础。该申请寻求支持，以继续我们对这些先天缺陷的基因组基础的调查。我们使用最先进的技术，比较基因组杂交微阵列（ACGH）来识别先天性泌尿生殖器缺陷儿童的染色体上的微观显微镜收益或损失。这项工作确定了染色体区域，其中相同的先天缺陷的无关患者表现出从头结构的染色体复制或缺失，或缺失太小，无法在核型上看到。经过临床验证的ACGH鉴定出约20％的患有泌尿生殖力的儿童的结构性染色体缺陷，这是小儿泌尿科医师今天可以使用的。因此，我们的第一个假设得到了证明：我们改善了这些ACGH儿童的诊断。我们试图继续鉴定先天性泌尿生殖器缺陷的遗传热点。重要的是，这项工作确定了许多候选基因，用于正常的人类泌尿生殖力发育和先天缺陷。基于当前的研究，我们有许多用于人类泌尿生殖道发育的候选基因尚待分析，我们的ACGH研究继续提供信息，并提出了新的研究领域。因此，我们的具体目标仍然与我们当前资助的提案相似。我们试图确定这些常见先天缺陷的基础的遗传和基因组缺陷。通过小鼠模型的产生和组织形态发生过程中的基因功能的定义，我们将继续展示基因特异性因果关系，而不仅仅是与先天缺陷的简单关联。这项研究的长期目标是改善先天性泌尿生殖缺陷的诊断，并确定泌尿生殖器遗迹儿童这种关键生物学过程失败的遗传基础。尽管大多数泌尿生殖道缺陷在儿童中被小儿泌尿科医生在手术中纠正，但我们寻求了解出生缺陷的原因，并知道是否有类似儿童会受到类似的困扰。该提案使用新颖的方法来提高我们对分子基础的理解，并提高我们诊断下尿和泌尿生殖器的常见出生缺陷的能力。