The multi-disciplinary research team will apply positional cloning and/or high-throughput sequencing techniques to DNA samples from several families with heritable myelodysplastic syndrome (MDS) to identify novel disease-associated loci. Novel image analysis software will be introduced to assess the feasibility of this technology to obtain objective measurements Indicative of dysplasia in histological specimens of pediatric patients with MDS.

SA1. IDENTIFY THE GENETIC LOCI RESPONSIBLE FOR FAMILIAL MDS

1. Use positional cloning, copy number variation and whole genome sequencing techniques to identify the loci responsible for familial pediatric MDS
2. Perform genome-wide single nucleotide polymorphism genotyping to map and clone novel MDS loci by using linkage mapping, homozygosity mapping, and copy number variation techniques
3. Sequence whole genomes, or exomes in order to identify novel MDS genes in heritable and apparently sporadic pediatric MDS

SA2. FURTHER DEVELOP PEDIATRIC MDS AND BMF PATIENT SAMPLE RESOURCES AND PERFORM PRELIMINARY ANALYSIS OF PATIENT CHARACTERISTICS, OUTCOMES AND HISTOLOGICAL FINDINGS

1. Grow existing tissue resources in the Pediatric MDS and BMF Registry and Tissue Repository by expanding to collection on a national level
2. Perform first interim data analysis of pediatric MDS to gather data to direct future clinical and translational studies
3. Determine feasibility of the use of advanced imaging analysis and machine learning as a more objective diagnostic tool in the morphological identification of MDS