Jump to: Authorized Access | Attribution | Authorized Requests

Study Description

The Centers for Mendelian Genomics project uses next-generation sequencing and computational approaches to discover the genes and variants that underlie Mendelian conditions. By discovering genes that cause Mendelian conditions, we will expand our understanding of their biology to facilitate diagnosis and new treatments.

Authorized Access
Publicly Available Data (Public ftp)
Study Inclusion/Exclusion Criteria

Prioritization Criteria:

  1. Likely Mendelian cause: The family has a highly penetrant severe and/or early onset phenotype, including those families with phenotypes matching a known but unsolved genetic condition. Families with multiple affected individuals, particularly cases that are consanguineous or large enough to obtain a significant LOD score through linkage, will be prioritized.
  2. Pre-screened for known genetic causes: For diseases with known genes, sample has undergone either targeted testing for the major genetic contributors to the phenotype, or exome sequencing.
  3. Likely recessive or de novo dominant genetic cause: Families with multiple affected siblings with unaffected parents, or with a known consanguineous relationship, will be favored over inherited dominant conditions. Probands with a strong suspicion of a de novo cause of disease (embryonic lethal/severe neonatal/pediatric disease) will also be prioritized if parental samples are available for trio analysis.
  4. Multiple cases: We will favor submissions for which there are multiple independent cases with the same rare phenotype.
  5. Detailed clinical data and additional samples are available: We will favor cases obtained by clinicians in active contact with the patient, for whom detailed medical records are available, and where obtaining additional clinical specimens and data are feasible.
  6. DNA and consent are available from multiple family members: We will prioritize cases where DNA samples from additional family members, especially parents and affected relatives, are available for study.
  7. Samples from a disease-relevant tissue are available for RNA-seq: We will prioritize cases when patient samples from a tissue known to be impacted by the disease phenotype, or a relevant cell line (such as differentiated iPS cells), are available for transcriptome analysis.
  8. Resources are available for detailed follow-up analyses: We will favor phenotypes for which there is clinical and biological/laboratory expertise available for the phenotype, and a clear path to targeted testing of candidate genes in other patients with similar phenotypes through local or international collaborations.

Molecular Data
TypeSourcePlatformNumber of Oligos/SNPsSNP Batch IdComment
Whole Exome Sequencing Illumina Rapid Capture Exome Enrichment Kit N/A N/A
Whole Exome Sequencing Illumina TruSeq Rapid Exome Library Prep Kit N/A N/A
Targeted Genotyping Illumina iSelect Custom Panel 7100 N/A Custom iSelect HTS Kit - Version 1.0
RNA Sequencing Illumina TruSeq RNA Library Preparation Kit V2 N/A N/A
RNA Sequencing Illumina TruSeq Stranded mRNA Sample Prep Kit N/A N/A
Whole Genome Sequencing KAPA Biosystems KAPA Library Preparation Kit N/A N/A KK8202 - KAPA Biosystems
Selected Publications
Diseases/Traits Related to Study (MeSH terms)
Links to Related Resources
Authorized Data Access Requests
Study Attribution
  • Principal
    • Daniel G. MacArthur. Broad Institute, Cambridge, MA, USA.
  • Principal Investigators
    • Heidi L. Rehm. Broad Institute, Cambridge, MA, USA.
  • Funding Sources
    • 1UM1HG008900-01 (Joint Center for Mendelian Genomics). National Institutes of Health, Bethesda, MD, USA.