Pronounced inter- and intrachromosomal variation in linkage disequilibrium across the zebra finch genome

Abstract

The extent of nonrandom association of alleles at two or more loci, termed linkage disequilibrium (LD), can reveal much about population demography, selection, and recombination rate, and is a key consideration when designing association mapping studies. Here, we describe a genome-wide analysis of LD in the zebra finch (Taeniopygia guttata) using 838 single nucleotide polymorphisms and present LD maps for all assembled chromosomes. We found that LD declined with physical distance approximately five times faster on the microchromosomes compared to macrochromosomes. The distribution of LD across individual macrochromosomes also varied in a distinct pattern. In the center of the macrochromosomes there were large blocks of markers, sometimes spanning tens of mega bases, in strong LD whereas on the ends of macrochromosomes LD declined more rapidly. Regions of high LD were not simply the result of suppressed recombination around the centromere and this pattern has not been observed previously in other taxa. We also found evidence that this pattern of LD has remained stable across many generations. The variability in LD between and within chromosomes has important implications for genome wide association studies in birds and for our understanding of the distribution of recombination events and the processes that govern them.

Figure 1.

Mean r² for distance bins of 1 Mb for macrochromosomes and microchromosomes plotted against physical distance (Mb).

Figure 2.

The extent of useful LD was negatively related to chromosome length and positively related to recombination rate. Observed and fitted relationship between the swept radius and recombination rate (left) and chromosome length (right).

Figure 3.

LD maps (LDU) and genetic maps (cM) plotted against physical distance along four macrochromosomes (Tgu1, Tgu2, Tgu4, and Tgu5) and four microchromosomes (Tgu15, Tgu17, Tgu19, and Tgu20). (Solid circles and black lines) LD map; (open gray squares and gray lines) genetic map. This figure demonstrates large regions of extended LD on the macrochromosomes, corresponding to low recombination in the center and high recombination at the ends. In contrast, this pattern is not consistently evident on the microchromosomes, where the relationship between LD and physical distance is mostly linear. See Supplemental Figs. S5.1–S5.4 for all chromosomes.

Figure 4.

Observed (filled circles) and fitted (lines) relationship of LD distance between adjacent markers and standardized distance from the center of the chromosome (Mb). Recombination is localized on the ends of the macrochromosomes, whereas it is more uniformly distributed on the microchromosomes.

Figure 5.

The total number of linkage disequilibrium units (LDU), GC content, number of genes, and heterozygosity per megabase (Mb) for two macrochromosomes (Tgu2, Tgu3) and two microchromosomes (Tgu12, Tgu13). See Supplemental Figs. S7.1–S7.3 for all chromosomes.