A reliable big data-based computational toolset for efficiently manipulating genome-wide variants, annotations and every-site coverage in NGS studies. SeqHBase uses a heuristic framework of inheritance information for detecting de novo, inherited homozygous or compound heterozygous mutations that may be disease-contributing in trios, nuclear families and/or extended families. It shows very good performance on three different examples of family based sequencing data and is scalable by virtue of its basis on MapReduce framework.