2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Identification of molecular modifiers of disease in a group of systematically phenotyped patients with Cystic Fibrosis

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This study aimed to identify molecular modifiers of disease in patients with Cystic Fibrosis (CF). CF is caused by over 2,000 variants in the CFTR locus, resulting in variable phenotypes. The multisystem nature, chronicity of symptoms, and presence of numerous variations make understanding the disease and selecting therapies challenging. The researchers hypothesized that this complexity is partly due to the presence of trans-modifiers.<br /><br />The study found known modifiers (>50% of patients) and candidate variations in novel candidate loci. These modifiers were associated with various phenotypes, including susceptibility to infection, failure to thrive, and nutrition. In some cases, these modifiers may represent additional treatment pathways.<br /><br />The researchers are currently working on the creation of an externally queryable CF modifiers repository. They are also conducting variant association analysis using variant, gene, and pathway burden testing.<br /><br />The study was supported by the Cystic Fibrosis Foundation and The Legacy of Angels Foundation. The references cited include a paper on the genetics and genomics of CF and a framework for variation discovery and genotyping using next-generation DNA sequencing data.<br /><br />The figures included in the document show the variant prioritization and analysis approach used in the study, the distribution of shared and total variants in the CFTR gene and four modifier genes, and the functional characterization of candidate modifiers.<br /><br />Overall, this study provides insights into the molecular modifiers of CF and their associations with different phenotypes, potentially contributing to the development of personalized treatments for patients with CF.

Asset Subtitle

Presenting Author - Gurpreet Kaur, Ph.D.; Co-Author - Donna M. Brown, MS; Co-Author - Brandon M. Wilk, BS; Co-Author - Manavalan Gajapathy, PhD; Co-Author - Tarun Karthik K. Mamidi, MS; Co-Author - Shaurita D. Hutchins, MS; Co-Author - Camille L. Birch, PhD; Co-Author - Felipe Massicano, PhD; Co-Author - Jinmyung Choi, PhD; Co-Author - Sangita G. Murali, PhD; Co-Author - Huichuan J. Lai, PhD, RD; Co-Author - Philip M. Farrell, MD, PhD; Co-Author - Elizabeth A. Worthey, PhD;

Meta Tag

Bioinformatics

Genome sequencing

Genotype-Phenotype Correlations

Identification of Disease Genes

NextGen Sequencing

Respiratory System

Variant Detection

Co-Author Donna M. Brown, MS

Co-Author Brandon M. Wilk, BS

Co-Author Manavalan Gajapathy, PhD

Co-Author Tarun Karthik K. Mamidi, MS

Co-Author Shaurita D. Hutchins, MS

Co-Author Camille L. Birch, PhD

Co-Author Felipe Massicano, PhD

Co-Author Jinmyung Choi, PhD

Co-Author Sangita G. Murali, PhD

Co-Author Huichuan J. Lai, PhD, RD

Co-Author Philip M. Farrell, MD, PhD

Co-Author Elizabeth A. Worthey, PhD

Presenting Author Gurpreet Kaur, Ph.D.

Keywords

molecular modifiers

Cystic Fibrosis

CFTR locus

phenotypes

trans-modifiers

susceptibility to infection

failure to thrive

nutrition

CF modifiers repository

variant association analysis