Chapter 2 - Clinical Applications of Genetics

Abstract

Researchers have been shifting the focus of genetic testing from Mendelian disorders towards identifying susceptibility alleles that predispose individuals to developing complex traits, such as diabetic nephropathy, and incorporating pharmacogenomic testing to predict drug-genome interactions. Genetic testing involves the analysis of chromosomes, deoxyribonucleic acid (DNA), ribonucleic acid (RNA), or specific metabolites in order to detect variants that are associated with human disease or a pharmacological response. Direct testing refers to gene-specific evaluation of a DNA and/or RNA sample. The linkage-based testing is an indirect method that examines the segregation of genetic markers located near or within the disease-causing gene with disease phenotypes within a family. Genetic testing increasingly holds the potential to inform clinical practice and impact the outcomes of patients with the disorders that disrupt the structure, function, and/or developmental patterning of the glomerulus, tubules, and urogenital tract, and those that predispose to renal cell tumors. One area where the use of genetic testing has increased rapidly is in the area of hereditary cancer, particularly in relation to hereditary breast/ovarian and hereditary bowel cancer syndromes. Genetic screening may also be of help in determining the chance of developing renal tumors in these disorders. Molecular diagnostic laboratories have developed numerous methods to scan DNA and/or RNA for mutations in specific disease genes or, in certain disorders such as cystic fibrosis, to screen for specific known mutations that cause disease in a high percentage of affected individuals. The current mainstay for molecular diagnosis involves sequence-based protocols that examine the exons and adjacent intronic regions of specific genes.