Positional Cloning of the Gene(s) Responsible for Alagille Syndrome

Conditions

Alagille Syndrome

Keywords

Chromosomal Deletion, Mutations, Paucity of Bile Ducts, Physical Map, Transcript Identification, Alagille Syndrome, Syndromic Bile Duct Paucity

Brief summary

The goal of the project is to identify and clone the gene(s) responsible for the Alagille Syndrome (AGS) by a positional cloning approach. The first step towards this goal is to define the smallest genomic candidate region for AGS at 20p12 and to begin to identify genes within this region which are, by definition, candidate genes for the disease. In a collaborative effort with clinician-investigators studying the Alagille syndrome, metaphase chromosomes and genomic DNA from affected individuals will be studied for subchromosomal deletions and for mutations in the candidate genes. Characterization of genes involved in Alagille syndrome could provide important insight into the pathophysiology of the disease, the development of normal liver and treatment of this disease. Recently, we and others found that mutations in Jagged1, a Notch1 receptor are responsible for Alagille Syndrome.

Detailed description

The goal of the project is to identify and clone the gene(s) responsible for the Alagille Syndrome (AGS) by a positional cloning approach. The first step towards this goal is to define the smallest genomic candidate region for AGS at 20p12 and to begin to identify genes within this region which are, by definition, candidate genes for the disease. In a collaborative effort with clinician-investigators studying the Alagille syndrome, metaphase chromosomes and genomic DNA from affected individuals will be studied for subchromosomal deletions and for mutations in the candidate genes. Characterization of genes involved in Alagille syndrome could provide important insight into the pathophysiology of the disease, the development of normal liver and treatment of this disease.

Related papers

No related papers found yet.

Interventions

None listed

Eligibility

Sex/Gender

ALL

Healthy volunteers

No

Inclusion criteria

All enrolled affected subjects, whose samples will be analyzed in this study, must meet the criteria for the clinical diagnosis of Alagille Syndrome (Syndromic Bile Duct Paucity) which include liver biopsy findings consistent with Alagille Syndrome and at least 3 of the 5 primary clinical criteria: cholestasis, characteristic face, posterior embryotoxon, butterfly vertebrae and cardiac findings.

Countries

United States

Outcome results