A computer-implemented method for determining a likelihood of a presence or absence of a genetic variation in a gene of interest in a genome of a subject where the genome also contains one or more counterpart genes to the gene of interest in the genome of the subject and the one or more counterpart genes in the genome of the subject are at least 80% identical to the gene of interest in the genome in the subject, comprising the steps of: (a) providing a modified reference genome comprising (i) the gene of interest and (ii) the one or more counterpart genes to the gene of interest, wherein at least 30% of nucleotides of the one or more counterpart genes of the modified reference genome are deleted or substituted with different nucleotides; (b) mapping sequence reads obtained from the subject to the modified reference genome, wherein (i) the sequence reads are obtained from a sample obtained from the subject, wherein the subject is diploid, using a massively parallel sequencing method, (ii) a subset of the sequence reads are obtained from the gene of interest in the genome of the subject and the one or more counterpart genes in the genome of the subject, and (iii) the subset of sequence reads map to the gene of interest of the modified reference genome and not to the one or more counterpart genes of the modified reference genome; and (c) determining the likelihood of a presence or absence of a genetic variation in the gene of interest in the genome of the subject according to the subset of sequence reads mapped to the gene of interest of the modified reference genome, wherein the absence of the genetic variation indicates the genetic variation is in neither the gene of interest in the genome of the subject nor the one or more counterpart genes in the genome of the subject, and the presence of the genetic variation indicates that the genetic variation is present in the gene of interest in the genome of the subject or the one or more counterpart genes in the genome of the subject, or both. (a) providing a modified reference genome comprising (i) the gene of interest and (ii) the one or more counterpart genes to the gene of interest, wherein at least 30% of nucleotides of the one or more counterpart genes of the modified reference genome are deleted or substituted with different nucleotides; (b) mapping sequence reads obtained from the subject to the modified reference genome, wherein (i) the sequence reads are obtained from a sample obtained from the subject, wherein the subject is diploid, using a massively parallel sequencing method, (ii) a subset of the sequence reads are obtained from the gene of interest in the genome of the subject and the one or more counterpart genes in the genome of the subject, and (iii) the subset of sequence reads map to the gene of interest of the modified reference genome and not to the one or more counterpart genes of the modified reference genome; and (c) determining the likelihood of a presence or absence of a genetic variation in the gene of interest in the genome of the subject according to the subset of sequence reads mapped to the gene of interest of the modified reference genome, wherein the absence of the genetic variation indicates the genetic variation is in neither the gene of interest in the genome of the subject nor the one or more counterpart genes in the genome of the subject, and the presence of the genetic variation indicates that the genetic variation is present in the gene of interest in the genome of the subject or the one or more counterpart genes in the genome of the subject, or both.