A High-Resolution SNP Array-Based Linkage Map Anchors a New Domestic Cat Draft Genome Assembly and Provides Detailed Patterns of Recombination

Abstract

High-resolution genetic and physical maps are invaluable tools for building accurate genome assemblies, and interpreting results of genome-wide association studies (GWAS). Previous genetic and physical maps anchored good quality draft assemblies of the domestic cat genome, enabling the discovery of numerous genes underlying hereditary disease and phenotypes of interest to the biomedical science and breeding communities. However, these maps lacked sufficient marker density to order thousands of shorter scaffolds in earlier assemblies, which instead relied heavily on comparative mapping with related species. A high-resolution map would aid in validating and ordering chromosome scaffolds from existing and new genome assemblies. Here, we describe a high-resolution genetic linkage map of the domestic cat genome based on genotyping 453 domestic cats from several multi-generational pedigrees on the Illumina 63K SNP array. The final maps include 58,055 SNP markers placed relative to 6637 markers with unique positions, distributed across all autosomes and the X chromosome. Our final sex-averaged maps span a total autosomal length of 4464 cM, the longest described linkage map for any mammal, confirming length estimates from a previous microsatellite-based map. The linkage map was used to order and orient the scaffolds from a substantially more contiguous domestic cat genome assembly (Felis catus v8.0), which incorporated ∼20 × coverage of Illumina fragment reads. The new genome assembly shows substantial improvements in contiguity, with a nearly fourfold increase in N50 scaffold size to 18 Mb. We use this map to report probable structural errors in previous maps and assemblies, and to describe features of the recombination landscape, including a massive (∼50 Mb) recombination desert (of virtually zero recombination) on the X chromosome that parallels a similar desert on the porcine X chromosome in both size and physical location.

RADseq provides unprecedented insights into molecular ecology and evolutionary genetics: comment on Breaking RAD by Lowry et al. (2016)

“…; Li et al . ). Finally, reduced recombination has been observed across several Mb sections of multiple chromosomes in collared flycatchers (Burri et al .…”

“…Recombination deserts spanning 50 Mb have been observed in cats (Li et al . ); 34 Mb recombination deserts have been found in pigs (Ai et al . ; Li et al .…”

“…In zebra finch, 'recombination deserts' have been observed to extend for over 100 Mb on multiple chromosomes and 90% of the total recombination in zebra finch is concentrated in only 23% of the genome (Backstrom et al 2010). Recombination deserts spanning 50 Mb have been observed in cats ; 34 Mb recombination deserts have been found in pigs (Ai et al 2015;Li et al 2016). Finally, reduced recombination has been observed across several Mb sections of multiple chromosomes in collared flycatchers (Burri et al 2015) and mouse (Shifman et al 2006).…”

A Beautiful Life: High Risk–High Payoff in Genetic Science

“…We constructed several panels of cat-rodent somatic cell hybrids and began mapping the cat genome (18). We built a linkage map with a breeding pedigree between house cats and a related species, leopard cats (Prionailurus bengalensis), developed at the NIH Animal Breeding facility in Poolesville, Maryland (19). This was exciting to me and sparked a career-long fascination (indeed, obsession) with the biology, evolutionary genetics, and medicine of cats (20)(21)(22)(23).…”

Recombination-aware phylogenomics unravels the complex divergence of hybridizing species.

“…To more thoroughly understand the interplay between local recombination rates, inferred interspecies gene flow and phylogenomic resolution in the cat family, we analyzed the distribution of phylogenetic signal across the genomes of 27 felid species in the context of recombination rates inferred from high-resolution linkage maps for the domestic cat (Menotti-Raymond et al 1999;Menotti-Raymond et al 2003;Li, Hillier, et al 2016). We found that phylogenomic signal is strongly influenced by ancient admixture, that it is partitioned within the nuclear genome by local recombination rates, and that the inferred species branching events are enriched on the X chromosome.…”