Genomic medicine and gene function implementation for an underserved population

PROJECT SUMMARY
Here we propose to advance the goal of NHGRI to implement genomic medicine and focus on individuals
who have not been able to afford DNA testing. The research takes place in the Department of Molecular and
Human Genetics at Baylor College of Medicine (BCM) and Texas Childrens Hospital (TCH). Our team of
clinicians, geneticists, computer scientists, genomicists and model organism researchers has had a five-year
term of success with the Undiagnosed Diseases Network (UDN) Model Organisms Screening Center (MOSC).
This has included successfully identifying a number of new disease genes such as EBF3, IRF2BPL, NACC1,
TBX2, TOMM70, CDK19, ACOX1, WDR37, and ATP5F1D. We propose to recruit 100 individuals from an
underserved population in Houston, Texas with suspected rare disease and without the means to pay for
DNA sequencing through insurance. We will provide whole-exome sequencing which will generate a CAP/CLIA
report that we anticipate could diagnose 35-40 individuals per year. The remaining individuals will then be
converted to a family-based trio exome design. All the sequencing costs of this project will be covered by
philanthrophic donation to our hospital and are not budgeted to the grant. We will make every effort to
diagnose the remaining 60 individuals per year through machine learning and informatics using the MARRVEL
platform, Drosophila functional studies of candidate genes and through ongoing 6 month, 12 month and 2 year
follow-up with the patients where we will use matchmaking efforts such as GeneMatcher and Matchmaker
exchange as well as our own genomic databases from the UDN and other studies to come to a genetic
diagnosis. All subjects will receive genetic counseling from a trained team and will provide us with valuable
medical, psychological and social data to guide how genomic implementation in an underserved population
is perceived, impacts care and impacts the family. This work will not only produce novel insights into rare
disease, diagnosis for undiagnosed families and an expanded role for genomics, it will guide us in the future
to provide genomics and functional research to serve all individuals regardless of their ability to pay.

Grant Number: 5R01HG011795-05
NIH Institute/Center: NIH
Principal Investigator: HUGO BELLEN