Method and apparatus for parent-of-origin disease allele detection for the diagnosis and management of genetic diseases

A method of assigning parent-of-origin to a haplotype, sub-haplotype or an allele associated with the haplotype, the method comprising:

• generating haplotypes of a genome;
• determining a differential methylation status of at least one imprinted differentially methylated region (iDMR) associated with each one of the haplotypes;
• and
• correlating the determined differential methylation status of the at least one iDMR to each one of the haplotypes to assign a parent-of-origin for each one of the haplotypes.

An apparatus for determining parent-of-origin of a haplotype, sub-haplotype or an allele associated with the haplotype, the apparatus comprising:

• a first sequencing apparatus for conducting a first sequencing technique to provide long-range phase information;
• a second sequencing apparatus for conducting a second sequencing technique to provide differential methylation status of at least one iDMR associated with the haplotype;
• and
• a processor for analyzing the long-range phase information and the differential methylation status of the at least one iDMR to determine a parent-of-origin of the haplotype, sub-haplotype, or allele associated with the haplotype.

A kit for determining parent-of-origin of a haplotype, sub-haplotype or an allele associated with the haplotype, the kit comprising:

• instructions for conducting a first sequencing technique to provide long-range phase information;
• instructions for conducting a second sequencing technique to provide differential methylation status of at least one iDMR associated with the haplotype;
• and
• instructions for combining the long-range phase information and the differential methylation status of the at least one iDMR to determine a parent-of-origin of the haplotope, sub-haplotype, or allele associated with the haplotype.