A method of determining a causative mutation of a disease or condition in one or more subjects affected by the disease or condition comprising: (a) screening a genome, optionally the whole genome of a subject affected by the disease or condition with an assay to provide information on one or more copy number variants (CNVs); (b) comparing via a computer, the information on the one or more CNVs from the subject's genome to a compilation of data comprising frequencies of CNVs in at least 100, 200, 500, 1,000, 2,000, 3,000, 5,000 or 10,000 subjects unaffected by the disease or condition, wherein said computer comprises computer executable logic that provides instructions for executing said comparison; (c) determining a statistical significance of the one or more CNVs to a disease or condition associated with a genotype from the comparison of step (b), or determining whether the one or more CNVs is present in the subject's genome but not present in the compilation of data from the comparison of step (b); (d) sequencing the one or more CNVs or genome regions encompassing the one or more CNVs determined to be statistically significant or present in the genome of the subject affected by the disease or condition but absent or present at lower frequency in subjects unaffected by the disease or condition according to step (c), in one or more subjects affected by the disease or condition, to identify a first set of one or more genetic variants; (e) sequencing the one or more CNVs or one or more genome regions encompassing the one or more CNVs determined to be statistically significant or present in the genome of the subject affected by the disease or condition but absent or present at lower frequency in subjects unaffected by the disease or condition according to step (c), in at least 100 subjects unaffected by the disease or condition, to identify a second set of one or more genetic variants; (f) determining a statistical significance of the first set of one or more genetic variants by comparing the sequencing information of step (d) to the sequencing information of step (e). (a) screening a genome, optionally the whole genome of a subject affected by the disease or condition with an assay to provide information on one or more copy number variants (CNVs); (b) comparing via a computer, the information on the one or more CNVs from the subject's genome to a compilation of data comprising frequencies of CNVs in at least 100, 200, 500, 1,000, 2,000, 3,000, 5,000 or 10,000 subjects unaffected by the disease or condition, wherein said computer comprises computer executable logic that provides instructions for executing said comparison; (c) determining a statistical significance of the one or more CNVs to a disease or condition associated with a genotype from the comparison of step (b), or determining whether the one or more CNVs is present in the subject's genome but not present in the compilation of data from the comparison of step (b); (d) sequencing the one or more CNVs or genome regions encompassing the one or more CNVs determined to be statistically significant or present in the genome of the subject affected by the disease or condition but absent or present at lower frequency in subjects unaffected by the disease or condition according to step (c), in one or more subjects affected by the disease or condition, to identify a first set of one or more genetic variants; (e) sequencing the one or more CNVs or one or more genome regions encompassing the one or more CNVs determined to be statistically significant or present in the genome of the subject affected by the disease or condition but absent or present at lower frequency in subjects unaffected by the disease or condition according to step (c), in at least 100 subjects unaffected by the disease or condition, to identify a second set of one or more genetic variants; (f) determining a statistical significance of the first set of one or more genetic variants by comparing the sequencing information of step (d) to the sequencing information of step (e).