Detecting runs of homozygosity (ROH)

Runs of homozygosity, abbreviated ROH, are stretches of DNA where a person carries two identical haplotypes inherited from a common ancestor on both their maternal and paternal sides. Short ROH (under 1Mb) are common in everyone because of background population history. Long ROH (over 5-8Mb) are a direct genomic signature of recent consanguinity in the family pedigree.

Sliding-window detection

The Haeckel ROH detector slides a 50-SNP window along each chromosome. A window is classified as homozygous when fewer than 1 of its SNPs is heterozygous and at least 95% of its SNPs are called. Adjacent homozygous windows are merged, and the merged segment is reported as a candidate ROH if its physical length exceeds a configurable minimum (default 1Mb for short ROH detection, 5Mb for clinically relevant long ROH).

F_ROH: summarising the signal

F_ROH is the fraction of the autosomal genome covered by ROH segments above a length threshold. F_ROH for ROH > 1.5Mb is sensitive to remote consanguinity (great-great-grandparents and beyond). F_ROH for ROH > 5Mb is sensitive to recent consanguinity (parents are themselves first or second cousins). Both are reported separately so the user can interpret the time depth of any signal.

Population baselines for F_ROH > 5Mb run from near zero in outbred European cohorts up to 0.05-0.10 in populations with traditional consanguineous marriage practices. A reading above 0.0625 suggests parents at the level of first-cousin relatedness; above 0.125 suggests something closer than that.

Clinical implications

High F_ROH increases the per-individual risk of autosomal recessive disease by exposing rare deleterious variants in the homozygous state. The platform flags F_ROH > 0.025 (suggesting recent consanguinity) so the user and any partner-screening process can take into account the elevated background risk of recessive conditions.