A genome-wide library of CB4856/N2 introgression lines of Caenorhabditis elegans

Abstract

Recombinant inbred lines (RILs) derived from Caenorhabditis elegans wild-type N2 and CB4856 are increasingly being used for mapping genes underlying complex traits. To speed up mapping and gene discovery, introgression lines (ILs) offer a powerful tool for more efficient QTL identification. We constructed a library of 90 ILs, each carrying a single homozygous CB4856 genomic segment introgressed into the genetic background of N2. The ILs were genotyped by 123 single-nucleotide polymorphism (SNP) markers. The proportion of the CB4856 segments in most lines does not exceed 3%, and together the introgressions cover 96% of the CB4856 genome. The value of the IL library was demonstrated by identifying novel loci underlying natural variation in two ageing-related traits, i.e. lifespan and pharyngeal pumping rate. Bin mapping of lifespan resulted in six QTLs, which all have a lifespan-shortening effect on the CB4856 allele. We found five QTLs for the decrease in pumping rate, of which four colocated with QTLs found for average lifespan. This suggests pleiotropic or closely linked QTL associated with lifespan and pumping rate. Overall, the presented IL library provides a versatile resource toward easier and efficient fine mapping and functional analyses of loci and genes underlying complex traits in C. elegans.

Figure 1.

Genotypes of the N2 x CB4856 introgression line (IL) population showing genome-wide coverage (Supplementary Table 1). The CB4856 introgressions depicted in green and light blue indicate the position of the crossover. Chromosomes are indicated next to the axes.

Figure 2.

Decrease in pumping rate over time and lifespan. (A) Distribution of the pumping rate averages per IL on Days 4, 6, 8 and 10. (B) Regression lines of pumping rate over time of the individual ILs (grey lines), CB4856 and N2 (black lines). (C) ILs ordered by average lifespan and the average lifespan of CB4856 and N2 (grey horizontal lines).

Figure 3.

Bin mapping of QTLs for average lifespan (A) and pumping rate (B) in the N2 x CB4856 IL population. Significance of a bin locus is indicated by the black line. QTLs determined by the bin with the ILs significantly different from N2 are indicated by the grey areas. Threshold (P = 0.001) is indicated by the red horizontal line. Individual ILs are shown by the green, blue or red horizontal lines that indicate their CB4856 introgression position. The thin black lines at the end of each introgression are the regions between the CB4856 and N2 marker and harbour the crossover. Green lines indicate the ILs with the trait values significantly lower than N2 (P < 0.01) and red lines show which ILs showed higher trait values than N2 (P < 0.01).