Tool for Rapid, Automated Phenotype Assignment of CYP2D6, CYP2C9, CYP2C19, and other highly polymorphic genes

A novel, automated system and method for deriving diploid functional haplotypes from phased or unphased genomic sequence information. The diploytpes can be used to predict the biological impact or phenotype of the individual. Proof of concept has been …
  • A novel, automated system, and method for deriving diploid functional haplotypes from phased or unphased genomic sequence information. The haplotypes can be used to predict the biological impact or phenotype of the individual.
  • Proof of concept has been shown utilizing the CYP2D6 gene, a highly polymorphic gene that also features diverse structural variations, including gene deletion, duplication, multiplication events, and rearrangements with the nonfunctional, neighboring CYP2D7 and CYP2D8 genes.
  • In addition to CYP2D6, the system has been validated with CYP2C9, CYP2C19, SLOC1B1, CYP2C8, DPYD, and CYP4F2genes and is extensible to any polymorphic locus in which a comprehensive library of functionally relevant haplotypes and defining variant sets can be determined, and for which paired short reads align unambiguously.

Website

https://cmh.flintbox.com/technologies/6B37A37C455547F5AFD4D959C722FB6D

Advantages

  • Uses NextGen sequencing to query the genome, unlike micro-array based services which rely on a subset of known variants
  • Independent in silicio evaluation shows 100% accuracy rate for CYP2C9 and CYP2C19 and 95% accuracy rate for CYP2D6
  • Can be used with whole-genome sequence data as well as reduced representation sequencing that can be generated at a fraction of the cost
  • May be able to detect or predict the consequences of novel variants

Potential Applications

  • Predict the activity of genes involved in drug Absorption, Distribution, Metabolism, Excretion, and Response (ADMER)activity for an individual
    • Use by caregivers to guide the selection of pharmaceuticals and the initial dose
    • Pharmacogenomic research in the development of psychotropic, cancer, pain and cardiovascular, and other drugs
  • Impute Human Leukocyte Antigen diplotypes to ensure proper matching in the transplant setting
  • Diagnosis of Autoimmune disease disorders such as Rheumatoid Arthritis, Diabetes Mellitus type 1, and Celiac disease
  • Deriving diploid function of other polymorphic haplotypes

Contact Information

Name: Marcia Molina

Email: mimolina@cmh.edu

Phone: 785-341-8112 (mobile)