Studies of linkage disequilibrium (LD) and its variation in the genome are of central importance for understanding evolutionary history, population structure, and selective sweeps. Extreme forms of the latter may result in runs of homozygosity (ROH). In human gene mapping, long ROHs are the basis for homozygosity mapping (HM) with length measured in terms of Mb (106 base pairs physical distance). LD varies greatly over the human genome so that long ROHs tend to occur preferentially in regions of high LD and ROHs of the same length in different regions are not strictly comparable. Thus, in human gene mapping, LD appears as a confounder that needs to be taken into account in the interpretation of ROHs. The effect of varying LD can be mitigated by working on a scale of centimorgans (cM, genetic distance) instead of Mb. We demonstrate this effect for HapMap 3 data on chromosome 19 and show examples with different ROH lengths depending on whether physical or genetic lengths are used. These results suggest that HM should preferably be done on genetic rather than physical distances.
Keywords: Homozygosity mapping; linkage disequilibrium; recombination.
© 2015 John Wiley & Sons Ltd/University College London.