Genetic Contributions to Newborn RDS and Childhood Interstitial Lung Diseases
To discover genomic variants associated with neonatal respiratory distress syndrome and childhood interstitial lung diseases, we use candidate gene-focused (multiplexed direct genomic selection) and unbiased (exome sequencing and whole genome sequencing) next generation sequencing strategies and advanced computational quality, coverage, and filtering methods. To predict function of discovered variants, we use a suite of algorithms that incorporate evolutionary conservation and known regulatory motifs. Finally, we use human cell culture model systems to test biologic function of discovered variants.
Discovery of Novel Candidate Genes Associated with Rare, Diagnostically Challenging Birth Defects in Newborn Infants and Children
To discover genomic variants associated with rare, diagnostically challenging birth defects in newborn infants and children, we use next generation sequencing (exome or whole genome sequencing) of affected infant/parent trios. We computationally identify rare variants (minor allele frequency <0.01) and predict function with a suite of algorithms that incorporate evolutionary conservation and known regulatory motifs. To prove causality of discovered variants, we use model systems to demonstrate function and replication of candidate gene loci or pathways in unrelated infants with similar phenotypes.
Genetic Epidemiology of Surfactant Dysfunction Mutations -
For subjects who are referred to us for unexplained or otherwise unusual symptoms of respiratory distress, we use the clinical course to determine which surfactant related genes are the most likely candidates, and resequence ABCA3, SFTPB, SFTPC, or NKX2-1 to find mutations that may predict or correlate with the subject’s clinical phenotype.