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Study Description

The purpose of this study is to identify new genetic causes of neurodevelopmental diseases (NDDs) in the Joubert syndrome (JS) spectrum. Joubert syndrome is a recessive disease characterized by cerebellar vermis hypoplasia. Our currently funded NINDS award entitled "Molecular characterization of Joubert syndrome" seeks to identify new genetic causes through a variety of molecular strategies. Although our previous strategies involved whole genome SNP-scans, followed by candidate gene sequencing to arrive at identification of new JS causes, we have recently moved to Whole Exome Sequencing (WES) as a highly efficient methodology that is optimized for recessive disease. In this pilot project, CIDR has sequenced DNA on probands from 20 inbred families with JS spectrum disorders in which known causes have been excluded, that have not previously undergone genome-wide SNP scans. These paired end reads will be subject to our established bioinformatics pipeline including HOMOZGYOSITY, SNP and INDEL callers in our lab to identify potentially deleterious sequence changes (PDSC). This is followed by analysis to include testing each PDSC for segregation in the whole pedigree, for occurrence in a ethnically-matched cohort, as well as a defined patient cohort patients, in order to validate new NDD genes.

  • Study Types: Cohort, Family, Exome Sequencing
  • dbGaP estimated ancestry components using GRAF-pop
  • Number of study subjects that have individual level data available through Authorized Access: 106

Authorized Access
Publicly Available Data (Public ftp)

Connect to the public download site. The site contains release notes and manifests. If available, the site also contains data dictionaries, variable summaries, documents, and truncated analyses.

Study Inclusion/Exclusion Criteria

The inclusion criteria are these cases with likely inherited NDD for which the genetic cause is not known or is not obvious and falls within the Joubert syndrome spectrum to include the MESH terms listed. Parents must be consanguineous, and there must be more than one affected member per family. In some instances, these will be affected siblings and in other families this will be affected cousins. The exclusion criteria are those cases likely due to non-genetic factors such as environmental or pregnancy/labor/delivery issues, any cases with neurodegenerative components, or cases in which the genetic cause is obvious or already known.

Molecular Data
TypeSourcePlatformNumber of Oligos/SNPsSNP Batch IdComment
Whole Exome Sequencing Illumina HiSeq Platform (indexed, 75bp, paired-end runs) N/A N/A
Whole Exome Sequencing Agilent SureSelect Human All Exon 50Mb Target Enrichment Kit N/A N/A
Study History

In 2000, we began to recruit families from the Middle East. We have identified several genes for Joubert syndrome and related disorders (JSRD) using homozygosity mapping. We expect that exome sequencing will increase the efficiency of gene discovery in these families.

Selected publications
Diseases/Traits Related to Study (MESH terms)
Links to Related Resources
Authorized Data Access Requests
Study Attribution