Basic elements of gene mapping and identification.

The Human Genome Project has vastly facilitated the localization, identification, and characterization of disease-related genes by means of positional cloning. Application of this technique has elucidated the pathophysiology of several inheritable cardiovascular disorders and will ultimately change the clinical evaluation of and approach to these diseases. Over the next several years, efforts aimed at gene identification, DNA sequencing, correlation of genetic and physical maps, and manipulation of large segments of DNA will lead to identification of numerous candidate genes for positional analysis and will provide ample opportunity to identify the genetic abnormalities in other cardiovascular disorders. Because of the importance and clinical implications of these advances, a conceptual understanding of this methodology is essential to the practicing clinician

Search for somatic 22q11.2 deletions in patients with conotruncal heart defects

A wide range of clinical variability in patients with 22q11.2 deletions has been demonstrated in numerous studies. Nevertheless, it is still an open question if major genetic factors contribute to clinical expression. Therefore one aim of this study was to investigate, if patients with 22q11.2 deletion and conotruncal heart defects show a "second hit" somatic 22q11.2 deletion in tissue from the conotruncus, heart vessels or thymus. The second aim was to analyse patients with conotruncal heart defects without 22q11.2 deletion in blood cells for somatic deletion mosaicism. We were able to study tissue samples from heart surgery from 23 patients, 9 of whom had 22q11 deletions by FISH analysis on metaphase spreads from peripheral lymphocytes. Analysis of 18 polymorphic markers from the 22q11.2 region in DNA prepared from thymus and/or heart vessels and/or conotruncus tissue and peripheral lymphocytes in each patient did not show any allelic loss. Thus somatic 22q11.2 deletions apparently do not play a major role in conotruncal heart defects in patients with or without germ line 22q11.2 deletion