Genetic Modifiers of Liver Disease Severity in Alagille Syndrome
阿拉吉尔综合征肝病严重程度的基因修饰
基本信息
- 批准号:8090799
- 负责人:
- 金额:$ 15.51万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2009
- 资助国家:美国
- 起止时间:2009-07-01 至 2014-06-30
- 项目状态:已结题
- 来源:
- 关键词:AffectAlagille SyndromeAttentionBiochemicalCandidate Disease GeneCardiacCholestasisClinicalCollaborationsCopy Number PolymorphismDatabasesDevelopmentDiseaseDisease ProgressionEnzymesFamilyGenesGeneticGenomicsHepaticHousingIndividualInternationalIntrahepatic bile ductItalyLaboratoriesLeadLiverLiver diseasesMethodologyMorbidity - disease rateMutationNotch Signaling PathwayOnline Mendelian Inheritance In ManPathway interactionsPatientsPatternPolandRecordsRecruitment ActivityResearch PersonnelSeveritiesSeverity of illnessSignaling Pathway GeneSpainStagingStratificationSystemTechniquesTestingTransplantationVariantbaseclinically relevantcohortdisease phenotypegenome wide association studygenome-wideimprovedkidney vascular structureliver transplantationmalformationmortalityoutcome forecast
项目摘要
PROJECT SUMMARY
This is a proposal to identify clinically relevant modifiers of the severity of hepatic disease in patients with
Alagille Syndrome (AGS) AGS is an autosomal dominant, multi-system, variably expressed disorder caused by
mutations in one of two Notch Signaling Pathway genes. Mutations in Jagged1 (JAG1) are found in 95% of
patients and mutations in Notch2 in less than 1%. AGS causes significant morbidity associated with liver,
cardiac, renal and vascular malformations. The liver disease in AGS is characterized pathologically by
intrahepatic bile duct paucity, with resulting cholestasis, and ranges from very mild (sub-clinical with only
biochemical abnormalities of liver enzymes) to severe, in which case liver damage is extensive and a
transplant is required. Mortality due to liver disease is about 5%. The highly variable expressivity is consistent
with the presence of modifying factors that contribute to expressivity. We hypothesize that there are genetic
modifiers of the severity of liver disease. We propose a multi-pronged approach to the identification of these
genetic modifiers. Using our well-characterized cohort of patients with AGS and JAG1 mutations, we will
compare patients with mild liver disease to patients with severe liver disease to look for evidence of genomic
differences between the two groups. Recognizing the importance of attaining adequate power for the proposed
studies, we will aggressively recruit additional patients. We will use multiple techniques to look for genetic
differences between the patients with mild liver disease versus those with severe liver disease. We will test for
association of copy number variants with liver disease severity. We will carry out a genome-wide association
study using random tagSNPs and SNPs in specific genomic regions (candidate genes). We anticipate that
identification of modifying factors for liver disease severity will have implications beyond Alagille syndrome
patients, and may point to modifiers of liver disease severity in other disorders associated with cholestasis.
项目总结
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Nancy Bettina Spinner其他文献
Nancy Bettina Spinner的其他文献
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{{ truncateString('Nancy Bettina Spinner', 18)}}的其他基金
Resolving Uncertainty in Alagille Syndrome Diagnostics
解决阿拉吉尔综合征诊断中的不确定性
- 批准号:
10734881 - 财政年份:2023
- 资助金额:
$ 15.51万 - 项目类别:
Training Program in the Genetic Basis of Pediatric Gastrointestinal Disorders
儿科胃肠道疾病遗传基础培训计划
- 批准号:
8883521 - 财政年份:2014
- 资助金额:
$ 15.51万 - 项目类别:
Training Program in the Genetic Basis of Pediatric Gastrointestinal Disorders
儿科胃肠道疾病遗传基础培训计划
- 批准号:
8666845 - 财政年份:2014
- 资助金额:
$ 15.51万 - 项目类别:
Genetic Modifiers of Liver Disease Severity in Alagille Syndrome
阿拉吉尔综合征肝病严重程度的基因修饰
- 批准号:
8502652 - 财政年份:2009
- 资助金额:
$ 15.51万 - 项目类别:
Genetic Modifiers of Liver Disease Severity in Alagille Syndrome
阿拉吉尔综合征肝病严重程度的基因修饰
- 批准号:
7883529 - 财政年份:2009
- 资助金额:
$ 15.51万 - 项目类别:
Genetic Modifiers of Liver Disease Severity in Alagille Syndrome
阿拉吉尔综合征肝病严重程度的基因修饰
- 批准号:
7661203 - 财政年份:2009
- 资助金额:
$ 15.51万 - 项目类别:
Genetic Modifiers of Liver Disease Severity in Alagille Syndrome
阿拉吉尔综合征肝病严重程度的基因修饰
- 批准号:
8097573 - 财政年份:2009
- 资助金额:
$ 15.51万 - 项目类别:
Genetic Modifiers of Liver Disease Severity in Alagille Syndrome
阿拉吉尔综合征肝病严重程度的基因修饰
- 批准号:
8306850 - 财政年份:2009
- 资助金额:
$ 15.51万 - 项目类别:
NOTCH SIGNALING PATHWAY LIGANDS IN CARDIOVASCULAR DISEASE
心血管疾病中的 NOTCH 信号通路配体
- 批准号:
6565108 - 财政年份:2002
- 资助金额:
$ 15.51万 - 项目类别:
NOTCH SIGNALING PATHWAY LIGANDS IN CARDIOVASCULAR DISEASE
心血管疾病中的 NOTCH 信号通路配体
- 批准号:
6302546 - 财政年份:2000
- 资助金额:
$ 15.51万 - 项目类别:
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