Translating knowledge into practice in the "post-genome" era.

Area of Science:

• Genomics and Human Health
• Biochemistry and Molecular Biology

Background:

• The Human Genome Project's completion marks a starting point for understanding genomic complexity.
• A
• human phenome project
• is needed to bridge the gap between genotype and phenotype.
• Genomic information requires biochemical and biological context to be clinically relevant.

Purpose of the Study:

• To highlight the complexity of genotype-phenotype relationships using phenylalanine hydroxylase (PAH) as an example.
• To emphasize the necessity of integrating biochemistry and biology for the advancement of genomic medicine.
• To advocate for the role of clinician scientists in translating genomic discoveries to clinical practice.

Main Methods:

• Analysis of genotype-phenotype correlations in phenylketonuria (PKU) and hyperphenylalaninemia.
• Conceptual framework for integrating genomic, biochemical, and clinical data.
• Discussion of the role of clinician scientists as intermediaries.

Main Results:

• Mutant PAH genotypes exhibit complex relationships with PKU/Hyperphenylalaninemia phenotypes.
• Genomics alone does not fully explain phenotypes; biochemical pathways are crucial.
• Clinician scientists are essential for implementing genomic medicine.

Conclusions:

• Translating genomic data into clinical applications requires a deep understanding of biochemistry and biology.
• The development of a "human phenome project" is crucial for advancing genomic medicine.
• Rebuilding the community of clinician scientists is vital for bridging the lab-to-bedside gap.