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Two percentage of the cat genome is a repetitive, feline-specific satellite sequence (FA-SAT) of 483 bp and 65% guanine-cytosine content. Previous chromosomal localization of the satellite has demonstrated the satellite's presence on several discrete regions of the telomeres of chromosomes, predominately on the D, E, and F chromosome groups. The recent assembly of the 1.9 x whole-genome shotgun (WGS) sequence of cat illustrates the challenge of the assembly of these large numbers of relatively short, similar sequences. Clones with paired end reads that include FA-SAT sequence have a high level of assembly discrepancies compared with clones with other types of repetitive elements, such as short interspersed nuclear elements (SINEs) and long interspersed nuclear elements (LINEs). The influence of the presence of FA-SAT but not SINEs and LINEs on genome assembly may likely reflect the evolutionary emergence of FA-SAT, which has lead to an excess of FA-SAT copies with identical sequence, which is less an issue with older, more diverse SINE and LINE sequences. The FA-SATs are restricted to a few hundred discrete regions of the cat genome, and associated errors in the assembly seem to be restricted to these loci. The findings regarding the feline-specific sequence should be considered in the pending 8x assembly of the cat genome. [ABSTRACT FROM AUTHOR]

Annotation features from the 1.9-fold whole-genome shotgun (WGS) sequences of domestic cat have been organized into an interactive web application, Genome Annotation Resource Fields (GARFIELD) (http://lgd.abcc.ncifcrf.gov) at the Laboratory of Genomic Diversity and Advanced Biomedical Computing Center (ABCC) at The National Cancer Institute (NCI). The GARFIELD browser allows the user to view annotations on a per chromosome basis with unplaced contigs provided on placeholder chromosomes. Various tracks on the browser allow display of annotations. A Genes track on the browser includes 20 285 regions that align to genes annotated in other mammalian genomes: Homo sapiens, Pan troglodytes, Mus musculus, Rattus norvegicus, Bos taurus, and Canis familiaris. Also available are tracks that display the contigs that make up the chromosomes and representations of their GC content and repetitive elements as detected using the RepeatMasker (http://www.repeatmasker.org). Data from the browser can be downloaded in FASTA and GFF format, and users can upload their own data to the display. The Felis catus sequences and their chromosome assignments and additional annotations incorporate data analyzed and produced by a multicenter collaboration between NCI, ABCC, Agencourt Biosciences Corporation, Broad Institute of Harvard and Massachusetts Institute of Technology, National Human Genome Research Institute, National Center for Biotechnology and Information, and Texas A&M. [ABSTRACT FROM AUTHOR]

Documenting genome diversity is important for the local biomedical communities and instrumental in developing precision and personalized medicine. Currently, tens of thousands of whole-genome sequences from Europe are publicly available, but most of these represent populations of developed countries of Europe. The uneven distribution of the available data is further impaired by the lack of data sharing. Recent whole-genome studies in Eastern Europe, one in Ukraine and one in Russia, demonstrated that local genome diversity and population structure from Eastern Europe historically had not been fully represented. An unexpected wealth of genomic variation uncovered in these studies was not so much a consequence of high variation within their population, but rather due to the "pioneer advantage." We discovered more variants because we were the first to prospect in the Eastern European genome pool. This simple comparison underscores the importance of removing the remaining geographic genome deserts from the rest of the world map of the human genome diversity. [ABSTRACT FROM AUTHOR]

The Puma lineage within the family Felidae consists of 3 species that last shared a common ancestor around 4.9 million years ago. Whole-genome sequences of 2 species from the lineage were previously reported: the cheetah (Acinonyx jubatus) and the mountain lion (Puma concolor). The present report describes a whole-genome assembly of the remaining species, the jaguarundi (Puma yagouaroundi). We sequenced the genome of a male jaguarundi with 10X Genomics linked reads and assembled the whole-genome sequence. The assembled genome contains a series of scaffolds that reach the length of chromosome arms and is similar in scaffold contiguity to the genome assemblies of cheetah and puma, with a contig N50 = 100.2 kbp and a scaffold N50 = 49.27 Mbp. We assessed the assembled sequence of the jaguarundi genome using BUSCO, aligned reads of the sequenced individual and another published female jaguarundi to the assembled genome, annotated protein-coding genes, repeats, genomic variants and their effects with respect to the protein-coding genes, and analyzed differences of the 2 jaguarundis from the reference mitochondrial genome. The jaguarundi genome assembly and its annotation were compared in quality, variants, and features to the previously reported genome assemblies of puma and cheetah. Computational analyzes used in the study were implemented in transparent and reproducible way to allow their further reuse and modification. [ABSTRACT FROM AUTHOR]

In addition to including one of the most popular companion animals, species from the cat family Felidae serve as a powerful system for genetic analysis of inherited and infectious disease, as well as for the study of phenotypic evolution and speciation. Previous diploid-based genome assemblies for the domestic cat have served as the primary reference for genomic studies within the cat family. However, these versions suffered from poor resolution of complex and highly repetitive regions, with substantial amounts of unplaced sequence that is polymorphic or copy number variable. We sequenced the genome of a female F1 Bengal hybrid cat, the offspring of a domestic cat (Felis catus) x Asian leopard cat (Prionailurus bengalensis) cross, with PacBio long sequence reads and used Illumina sequence reads from the parents to phase >99.9% of the reads into the 2 species' haplotypes. De novo assembly of the phased reads produced highly continuous haploid genome assemblies for the domestic cat and Asian leopard cat, with contig N50 statistics exceeding 83 Mb for both genomes. Whole-genome alignments reveal the Felis and Prionailurus genomes are colinear, and the cytogenetic differences between the homologous F1 and E4 chromosomes represent a case of centromere repositioning in the absence of a chromosomal inversion. Both assemblies offer significant improvements over the previous domestic cat reference genome, with a 100% increase in contiguity and the capture of the vast majority of chromosome arms in 1 or 2 large contigs. We further demonstrated that comparably accurate F1 haplotype phasing can be achieved with members of the same species when one or both parents of the trio are not available. These novel genome resources will empower studies of feline precision medicine, adaptation, and speciation. [ABSTRACT FROM AUTHOR]

A diverse group of genes are involved in the tooth development of mammals. Several studies, focused mainly on mice and rats, have provided a detailed depiction of the processes coordinating tooth formation and shape. Here we surveyed 236 tooth-associated genes in 39 mammalian genomes and tested for signatures of selection to assess patterns of molecular adaptation in genes regulating mammalian dentition. Of the 236 genes, 31 (~13.1 %) showed strong signatures of positive selection that may be responsible for the phenotypic diversity observed in mammalian dentition. Mammalian-specific tooth-associated genes had accelerated mutation rates compared with older genes found across all vertebrates. More recently evolved genes had fewer interactions (either genetic or physical), were associated with fewer Gene Ontology terms and had faster evolutionary rates compared with older genes. The introns of these positively selected genes also exhibited accelerated evolutionary rates, which may reflect additional adaptive pressure in the intronic regions that are associated with regulatory processes that influence tooth-gene networks. The positively selected genes were mainly involved in processes like mineralization and structural organization of tooth specific tissues such as enamel and dentin. Of the 236 analyzed genes, 12 mammalian-specific genes (younger genes) provided insights on diversification of mammalian teeth as they have higher evolutionary rates and exhibit different expression profiles compared with older genes. Our results suggest that the evolution and development of mammalian dentition occurred in part through positive selection acting on genes that previously had other functions. [ABSTRACT FROM AUTHOR]

A recent genome-wide study showed that the single nucleotide polymorphisms (SNPs) in the HLA-DP region were associated with chronic hepatitis B virus (HBV) infection in Japanese and Thai persons. We tested the effects of HLA-DP SNPs for all major HBV outcomes in Han Chinese (n = 1742): HBV resistance, clearance, chronic infection, cirrhosis, and hepatocellular carcinoma. HLA - DPA1 rs3077 T was strongly associated with decreased risk of chronic HBV infection (odds ratio, .62; P = .001), consistent with the previous report. We showed for the first time to our knowledge that it is a predictor for HBV clearance (odds ratio, 2.41; P < .001). However, rs3077 was not associated with the development of cirrhosis or hepatocellular carcinoma. [ABSTRACT FROM PUBLISHER]

The SILVER locus has been mapped in the domestic cat, identifying a unique genomic location distinct from that of any known reported gene associated with silver or hypopigmentation in mammals. A demonstrated lack of linkage to SILV, the strong candidate gene for silver, led to the initiation of a genome scan utilizing 2 pedigrees segregating for silver coat color. Linkage mapping defined a genomic region for SILVER as a 3.3-Mb region, (95.87-99.21 Mb) on chromosome D2, (peak logarithm of the odds = 10.5, θ = 0), which displays conserved synteny to a genomic interval between 118.58 and 121.85 Mb on chromosome 10 in the human genome. In the domestic cat, mutations at the SILVER locus suppress the development of pigment in the hair, but in contrast to other mammalian silver variants, there is an apparently greater influence on the production of pheomelanin than eumelanin pigment. The mapping of a novel locus for SILVER offers much promise in identifying a gene that may help elucidate aspects of pheomelanogenesis, a pathway that has been very elusive, and illustrates the promise of the cat genome project in increasing our understanding of basic biological processes of general relevance for mammals. [ABSTRACT FROM AUTHOR]

A comprehensive genetic linkage map of the domestic cat X chromosome was generated with the goal o localizing the genomic position of the classic X-linked orange (O) locus. Microsatellite markers with an average spacing of 3 Mb were selected from sequence traces of the cat 1.9X whole genome sequence (WGS), including the pseudoautosomal region 1 (PAR1). Extreme variation in recombination rates (centimorgans per megabase) was observed along the X chromosome, ranging from a virtual absence of recombination events in a region estimated to he >30 Mb to recombination frequencies of 15.7 cM/Mb in a segment estimated to be <0.3 Mb. This detailed linkage map was applied to position the X-linked orange gene, placing this locus on the q arm of the X chromosome, as opposed to a previously reported location on the p arm. Fine mapping placed the locus between markers at positions 106 and 116.8 Mb in the current 1.9X-coverage sequence assembly of the cat genome. Haplotype analysis revealed potential recombination events that could reduce the size of the candidate region to 3.5 Mb and suggested multiple origins for the orange phenotype in the domestic cat. Furthermore, epistasis of orange over nonagouti was demonstrated at the genetic level. [ABSTRACT FROM AUTHOR]

Translocation of mtDNA into the nuclear genome, also referred to as numt, was first reported in the domestic cat (Felis catus) by Lopez et al. (1994). The Lopez-numt consisted of a translocation of 7.9 kbp of mtDNA that inserted into the domestic cat chromosome D2 around 1.8 million years ago. More than a decade later, the release of the domestic cat whole-genome shotgun sequences (1.9 x coverage) provides the resource to obtain more comprehensive insight into the extent of mtDNA transfer over time in the domestic cat genome. MegaBLAST searches revealed that the cat genome harbors a wide variety of numts (298 320 bp), one-third of which likely correspond to the Lopez-numt tandem repeat, whereas the remaining numts are probably derived from multiple independent insertions, which in some cases were followed by segmental duplication after insertion in the nucleus. Numts were detected across most cat chromosomes, but the number of numts assigned to chromosomes is underestimated due to the relatively high number of numt sequences with insufficient flanking sequence to map. The catalog of cat numts provides a valuable resource for future studies in Felidae species, including its use as a tool to avoid numt contaminations that may confound population genetics and phylogenetic studies. [ABSTRACT FROM AUTHOR]

Comparisons of the genomic structure of 3 mammalian major histocompatibility complexes (MHCs), human HLA, canine DLA, and feline FLA revealed remarkable structural differences between HLA and the other 2 MHCs. The 4.6-Mb HLA sequence was compared with the 3.9-Mb DLA sequence from 2 supercontigs generated by 7x whole-genome shotgun assembly and 3.3-Mb FLA draft sequence. For FLA, we confirm that 1) feline FLA was split into 2 pieces within the TRIM (member of the tripartite motif) gene family found in human HLA, 2) class II, III, and I regions were placed in the pericentromeric region of the long arm of chromosome B2, and 3) the remaining FLA was located in subtelomeric region of the short arm of chromosome B2. The exact same chromosome break was found in canine DLA structure, where class II, III, and I regions were placed in a pericentromeric region of chromosome 12 whereas the remaining region was located in a subtelomeric region of chromosome 35, suggesting that this chromosome break occurred once before the split of felid and canid more than 55 million years ago. However, significant differences were found in the content of genes in both pericentromeric and subtelomeric regions in DLA and FLA, the gene number, and amplicon structure of class 1 genes plus 2 other class 1 genes found on 2 additional chromosomes; canine chromosomes 7 and 18 suggest the dynamic nature in the evolution of MHC class 1 genes. [ABSTRACT FROM AUTHOR]

Topical literature and Web site databases provide genome sizes for ∼4,000 animal species, invertebrates and vertebrates, 330 of which are mammals. We provide the genome size for 67 mammalian species, including 51 never reported before. Knowledge of genome size facilitates sequencing projects. The data presented here encompassed 5 Metatheria (order Didelphimorphia) and 62 Eutheria: 15 Xenarthra, 24 Euarchontoglires (Rodentia), as well as 23 Laurasiatheria (22 Chiroptera and 1 species from Perissodactyla). Already available karyotypes supplement the haploid nuclear DNA contents of the respective species. Thus, we established the first comprehensive set of genome size measurements for 15 Xenarthra species (armadillos) and for 12 house-mouse species; each group was previously represented by only one species. The Xenarthra exhibited much larger genomes than the modal 3 pg DNA known for mammals. Within the genus Mus, genome sizes varied between 2.98 pg and 3.68 pg. The 22 bat species we measured support the low 2.63 pg modal value for Chiroptera. In general, the genomes of Euarchontoglires and Laurasiatheria were found being smaller than those of (Afrotheria and) Xenarthra. Interspecific variation in genome sizes is discussed with particular attention to repetitive elements, which probably promoted the adaptation of extant mammals to their environment. [ABSTRACT FROM AUTHOR]