Deborah I. Ritter, PhD

Identifying De-novo and Inherited Variants associated with Cancer Predisposition

Individuals with early childhood cancers and familial history of cancer can be a resource for discovery of novel genes involved with cancer predisposition. Identifying rare germline variants is challenging, as there is an ever-growing number of predicted damaging variants, and variant functional predictors can be unreliable. To prioritize variant and gene discovery, I focus on integrating familial variants, control datasets from large external sources such as ExAC, 1K Genomes, Exome Variant Server, and from internal sequence and annotation-matched controls, along with gene functional analysis. Project Mentors: Drs. Sharon Plon, David Wheeler

Genomic Sensitivity to Ionizing Radiation

Ionizing radiation is used to treat tumors, but in rare cases individuals with constitutional damage to DNA repair pathways can experience ionizing radiation related adverse events. Through the Texas Children’s Cancer Center and Genetics Consult Service at Texas Children’s Hospital, Dr. Sharon Plon has identified three families with adverse events or cellular evidence of ionizing radiation sensitivity. We have identified candidate genes in these families and are staging laboratory experiments to understand and characterize their function, as well as expand the search for other individuals with adverse events of radiation treatment. Project Mentors: Drs. Sharon Plon, David Wheeler

Detecting Rare Structural Variation

Tumor and constitutional genomes can undergo large structural changes such as translocations, inversions, and large duplications, deletions and insertions. I have developed a practical method to identify rare structural variation from outputs of programs such as CREST and BreakDancer, using familial pedigree and un-related control sets, with pipelined annotation, filtering and imaging. We have discovered the breakpoint genes of constitutional balanced translocations (see publications). I plan to supplement the control set content with public databases, as well as focus on improved identification of inversions and constitutional translocations. Project Mentors: Drs. Sharon Plon, David Wheeler

Detecting Rare, Functionally and Clinically Important Coding and Noncoding Variant Events

With an estimate of ~98% of the genome in noncoding bases, variants (both structural and SNV/INDEL) in these regions need improved characterization. Highly conserved noncoding regions (such as enhancers) can drive tissue-specific expression and are known to regulate fine-control of developmental genes. I integrate known enhancer sites from a dataset I created in graduate school and other multiple experimental and predictive sources, as well as noncoding data from ENCODE datasets into whole genome SNV/INDEL and SV analysis to identify variants in candidate functional noncoding regions. I plan to develop this analysis and filtering approach, identify candidate sites from whole genome sequencing of individuals with developmental congenital anomalies, and validate/characterize the variant noncoding regions using zebrafish as a model organism. Project Mentors: Drs. Jeffrey Chuang, Sharon Plon, David Wheeler

Bioinformatics and Medical Genomics Education (Academic and Public)

I am continually learning and developing teaching and communication skills that aid in making bioinformatics concepts approachable and intriguing for students and for public audiences. With the advent of personalized medicine, it is more critical than ever that the public can understand how genomic data is created and analyzed, and the ethical questions involved. I am focusing my interests on introducing learners without a background in science or bioinformatics to biological and ethical concepts in genomic medicine. Mentors: Drs. Gloria Regisford, Debra Murray, Gayle Slaughter, Kim Worley, David Wheeler, Jeffrey Chuang, Gabor Marth

Working Groups & Expert Panels

• Ancestry and Diversity Working Group
• Biocurator
• Breast/Ovarian Cancer Gene Curation Expert Panel
• Cancer Variant Interpretation
• ClinGen Community Curation (C3)
• Clinical Domain Working Groups
• Colon Cancer Gene Curation Expert Panel
• Copy Number Variant Interpretation Guidelines
• Data Access, Protection, and Confidentiality
• DICER1 and miRNA-Processing Gene Variant Curation Expert Panel
• Education, Coordination and Training
• Hereditary Cancer CDWG
• Hereditary Cancer Gene Curation Expert Panel
• InSiGHT Hereditary Colorectal Cancer/Polyposis Variant Curation Expert Panel
• Justice, Equity, Diversity, and Inclusion (JEDI) Coordination Team
• Neurofibromatoses and Schwannomatosis Variant Curation Expert Panel
• Partnership
• Pediatric Cancer Taskforce
• Somatic Cancer CDWG
• Somatic/Germline Variant Curation
• Steering Committee
• TP53 Variant Curation Expert Panel
• VHL Variant Curation Expert Panel