Li Gang, Hillier LaDeana W, Grahn Robert A, Zimin Aleksey V, David Victor A, Menotti-Raymond Marilyn, Middleton Rondo, Hannah Steven, Hendrickson Sher, Makunin Alex, O'Brien Stephen J, Minx Pat, Wilson Richard K, Lyons Leslie A, Warren Wesley C, Murphy William J
Department of Veterinary Integrative Biosciences, Interdisciplinary Program in Genetics, Texas A&M University, College Station, Texas 77843.
McDonnell Genome Institute, Washington University School of Medicine, St. Louis, Missouri 63108.
G3 (Bethesda). 2016 Jun 1;6(6):1607-16. doi: 10.1534/g3.116.028746.
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.
高分辨率遗传图谱和物理图谱是构建精确基因组组装以及解读全基因组关联研究（GWAS）结果的宝贵工具。先前的遗传图谱和物理图谱为家猫基因组高质量草图组装提供了锚定，使得人们能够发现众多与遗传性疾病以及生物医学和育种领域感兴趣的表型相关的基因。然而，这些图谱缺乏足够的标记密度来对早期组装中的数千个较短支架进行排序，早期组装严重依赖与相关物种的比较图谱。高分辨率图谱将有助于验证和排列现有及新基因组组装中的染色体支架。在此，我们基于对来自多个多代家系的453只家猫在Illumina 63K SNP芯片上进行基因分型，描述了家猫基因组的高分辨率遗传连锁图谱。最终图谱包含相对于6637个具有唯一位置的标记放置的58,055个SNP标记，分布在所有常染色体和X染色体上。我们最终的两性平均图谱的常染色体总长度为4464厘摩，这是所描述的任何哺乳动物中最长的连锁图谱，证实了先前基于微卫星图谱的长度估计。该连锁图谱用于对来自一个连续性显著更高的家猫基因组组装（Felis catus v8.0）的支架进行排序和定向，该组装纳入了约20倍覆盖度的Illumina片段 reads。新的基因组组装在连续性方面有显著改进，N50支架大小几乎增加了四倍，达到18 Mb。我们利用这张图谱报告先前图谱和组装中可能存在的结构错误，并描述重组景观的特征，包括X染色体上一个巨大的（约50 Mb）重组荒漠（几乎零重组），其大小和物理位置与猪X染色体上的类似荒漠相似。
