We used the Bowtie short-read alignment program [11] to screen all sequence reads against the BRCA1 and BRCA2 regions (located on chromosomes 17 and 13, respectively) and against a set of 68 known mutations from the Online Mendelian Inheritance in Man (OMIM) database (see Methods). The size of the datasets ranged from 2.8 to 4.1 billion reads for each genome, with most reads being 35–36 bp. The BRCA genomic regions are each about 80–90 kb; with these small target sequences Bowtie is extremely fast. Using only a single 2.4 GHz processor, Bowtie aligned reads at 127 million reads per hour, and alignment of the largest of our datasets took about 8 hours. Thus despite the enormous number of reads for each genome, screening was relatively fast.

In the Asian and African males, we found no evidence for any of the 68 deleterious mutations in BRCA1 and BRCA2. The Caucasian female had no mutations at 67 of the 68 sites, but she has a heterozygous mutation at one site in BRCA2. At this location, 26 reads match the mutant base (C) and 24 reads match the normal base (A). This A-C mutation causes a single amino acid change, N372 H, in exon 10, which in homozygous form was originally reported to carry a 30-40% increased risk of breast cancer [12, 13], although a subsequent study reported no increased cancer risk [14].

Note that the 68 mutations used in this proof-of-concept assay do not represent a comprehensive list of BRCA mutations. We used OMIM as our primary source, but other databases have much larger lists of BRCA mutations (for example the Human Gene Mutation Database [15] lists 1,215 mutations for BRCA1 and 966 for BRCA2). Most of these additional mutations could easily be added to our test, simply by incorporating them in the sequence index file described below. The software can be extended to other genes by creating new index files for those genes.

If free software can be used to diagnose human genetic mutations, then individuals will be able to run their own tests in the privacy of their own homes. Fundamentally, this seems no different from measuring one's temperature or blood pressure, but because of gene patents, the act of reading one's own genome may require the permission of a private company. It is hard to envision how the patent holders can enforce their claims in this scenario. Our contention is that these patents never should have been awarded, and that no private entity should have rights to the naturally occurring gene sequences in every human individual.