System and method for the computational prediction of expression of single-gene phenotypes

A method of determining a probability of a virtual progeny having one or more phenotypes Phj each associated with a single gene Qj, the method implemented by a computer processor executing program instructions, the method comprising the steps of:

• a. generating a haplopath Hp={h1p, h2p, . . . , hNp} including a single allele hipε(1,2) at each of a plurality of loci (i=1, . . . , N) from a genome profile of a potential parent (p);
• b. assigning a variance score sip to each of a plurality of the alleles hip in the haplopath, each of the variance scores sip indicating a probability that the allele hip results in altering gene product from gene Qj in the progeny;
• c. associating each variant allele hip1, which has a variance score sip indicating a non-zero probability, with a corresponding one of a plurality of (k=1, . . . , Nj) variant alleles hkp known to alter the gene product from gene Qj;
• d. for each gene Qj, assigning a gene-specific penetrance score ŝj,kp to each of the (Nj) variant alleles hkp associated with the gene Qj;
• e. for each gene Qj, determining a probability of altering the gene product from gene Qj in the virtual progeny of the parent (p) based on the gene-specific penetrance scores ŝj,kp of the plurality of (Nj) variant alleles hkp;
• and
• f. for each gene Qj, outputting the probability of altering the gene product or a derivation of the probability of altering the gene product.

A method of determining a probability of having a phenotype in a virtual progeny, the method implemented by a computer processor executing program instructions, the method comprising the steps of:

• a. generating a virtual progeny genome sampling G, wherein at each of a plurality of genetic loci i=1, . . . , N the sampling comprises one allele hip1 from a first genome profile of a first potential parent (p1) and one allele hip2 from a second genome profile of a second potential parent (p2);
• b. using the processor, comparing genotypes of said virtual progeny genome sampling G to one or more databases of genotype-phenotype associations to determine a phenotype associated with database genotypes matching genotypes of said virtual progeny genome sampling G, wherein the phenotype is associated with a penetrance value;
• c. using the processor, generating a random number to determine if the virtual progeny is predicted to have the phenotype;
• d. wherein if the virtual progeny is predicted to have the phenotype, using the processor, associating the penetrance value with a degree of expressivity of the phenotype in the virtual progeny.