BAK1 Gene Variation: the doubts remain

Introduction Since Gottlieb et al. [2009] published some intriguing sequence differences between DNA obtained from abdominal aortic (AA) tissue and blood, the scientific community has been attempting to understand their findings. Dr. Gottlieb’s group was primarily interested in performing case-control association analyses in abdominal aortic aneurysm (AAA) patients. However, instead of obtaining a significant association, they realized that both diseased and nondiseased AA tissues contained polymorphisms which were not observed in the matching blood samples. Dr. Hatchwell [2010] has proposed that the BAK1 gene variants were likely due to sequencing of a processed gene on chromosome 20. However, in response, Dr. Gottlieb and coauthors [2010] have argued that “some but not all of the sequence changes present in the BAK1 sequence of our abdominal aorta samples are also present in the chromosome 20 BAK1 sequence. However, all the AAA and AA cDNA samples are identical to each other and different from chromosome 20 BAK1 sequence at amino acids 2 and 145”. I have been following this discussion because I have independently reached almost the same conclusion as Dr. Hatchwell did [Yamagishi, 2009], and, unfortunately, the response from Dr. Gottlieb and his co-authors seems to me to be unsatisfactory for the reasons listed below.