Reconstructing parent genomes using siblings and other relatives.

Area of Science:

• Genetics and Genomics
• Bioinformatics
• Population Genetics

Background:

• Reconstructing ancestral DNA from descendants offers significant potential for phenotypic analyses, including association and genetic nurture studies.
• Accurate reconstruction of ancestral genotypes can improve pedigree analysis and provide insights into ancestral populations and their phenotypes.

Approach:

• HAPI-RECAP leverages HAPI2's sibling phasing output to infer parent haplotypes.
• It combines Identity by Descent (IBD) between reconstructed parents and relatives to resolve segment origins.
• The method utilizes inherited crossovers and sex-specific genetic maps to infer parental sexes.

Key Points:

• HAPI2 reconstructs substantial fractions of missing parent DNA (average 90.3% in 3-4 child families).
• HAPI-RECAP infers 33.2%-96.6% of parental genotypes (average 70.6% in 4-child families) with error rates comparable to direct genotyping (<10^-3).
• Parental sexes are inferred with 100% accuracy using IBD-linked segments, and reconstruction is possible even without IBD.

Conclusions:

• HAPI-RECAP enables high-quality parent genotype reconstruction from sibling data.
• This method holds promise for leveraging large, implicitly collected family datasets in genetic research.
• The ability to reconstruct ancestral DNA opens new avenues for genetic association and nurture studies.