whole Exome Sequencing Of A Family With 3 Sibling Affected By Bicuspid Aortic Valve Disease

Background: Bicuspid aortic valve (BAV) is the most common cardiac malformation affecting 1-2% people worldwide. Despite its high prevalence, the pathogenesis of BAV is largely undetermined, although gene mutations leading to alterations in cell migration and signal transduction, in conjunction with non-genetic factors such as blood flow during valvulogenesis, may contribute to its formation prenatally. Objective: The determination of genetic factors contributing to the presentation of BAV in a family with three affected daughters. Methods: We applied next generation whole exome sequencing (>3Gigabases per individual) to high quality DNA from the blood samples of the three affected daughters and their unaffected parents. The >36.000.000 reads of each of the 5 individuals were analyzed with the bioinformatics tools Burrow-Wheeler Aligner, SOAPsnp, Sam tools, Varscan, and GATK to identify single nucleotide polymorphisms and insertions/deletions. Results: We identified over 38,000 SNPs and 3,400 Indels in ea...