Look Over the Horizon - Chicken Linkage Disequilibrium is Much More Complex Over Much Longer Distance than Previously Appreciated

Abstract BackgroundAppreciable Linkage Disequilibrium (LD) is commonly found between pairs of loci close to one another, decreasing rapidly with distance between the loci. This provides the basis studies to map Quantitative Trait Loci Regions (QTLRs), where it is custom to assume that the closest sites to a significant markers are the prime candidate to be the causative mutation. Nevertheless, Long-Range LD (LRLD) can also be found among well-separated sites. LD blocks are runs of genomic sites all having appreciable LD with one another. High LD and LRLD are often separated by genomic sites with which they have practically no LD. Thus, not only can LD be found among distant loci, but also its pattern may be complex, comprised of fragmented blocks. Here, chicken LRLD and LD blocks, and their relationship with previously described Marek’s Disease (MD) QTLRs, were studied in an F6 population from a full-sib advanced intercross line, and in eight commercial pure layer lines. Genome wide LRLD was studied in the F6 population by random samples of non-syntenic and syntenic marker pairs. To illustrate the relationship with QTLRs, LRLD and LD blocks in and between the MD QTLRs were studied by all possible marker pairs.Results LRLD was defined as r2 ≥ 0.7 over a distance ≥ 1 Mb, and 1.5% of all syntenic marker pairs were classified as LRLD. Complex fragmented and interdigitated LD blocks were found, ranging over distances from a few hundred to a few millions bases. Vast high, long-range, and complex LD was found between two of the MD QTLRs. Cross QTLRs STRING networks and gene interactions suggested possible origins of the exceptional LD between these two QTLRs.ConclusionsAll sites with high LD with a significant marker should be considered as candidate for the causative mutation, but, unlike the custom assumption, the causative mutation is not necessarily the one closest to the significant marker. Rather, the present results show that it can be located at a much larger distance from a significant marker than previously appreciated, beyond closer mutations. Thus, LRLD range and LD block complexity must be accounted for while interpreting genetic mapping studies.