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1. Ultracontinuous Single Haplotype Genome Assemblies for the Domestic Cat ( Felis catus ) and Asian Leopard Cat ( Prionailurus bengalensis )

   https://doi.org/10.1093/jhered/esaa057  

   Bredemeyer, Kevin R ; Harris, Andrew J ; Li, Gang ; Zhao, Le ; Foley, Nicole M ; Roelke-Parker, Melody ; O’Brien, Stephen J ; Lyons, Leslie A ; Warren, Wesley C ; Murphy, William J ( December 2020 , Journal of Heredity)

   Shapiro, Beth (Ed.)

   Abstract 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. 

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2. Comparison of Antimicrobial-Resistant Escherichia coli Isolates from Urban Raccoons and Domestic Dogs

   https://doi.org/10.1128/AEM.00484-21  

   Worsley-Tonks, Katherine E. ; Gehrt, Stanley D. ; Miller, Elizabeth A. ; Singer, Randall S. ; Bender, Jeff B. ; Forester, James D. ; McKenzie, Shane C. ; Travis, Dominic A. ; Johnson, Timothy J. ; Craft, Meggan E. ( July 2021 , Applied and Environmental Microbiology)

   Elkins, Christopher A. (Ed.)

   ABSTRACT Wildlife can be exposed to antimicrobial-resistant bacteria (ARB) via multiple pathways. Spatial overlap with domestic animals is a prominent exposure pathway. However, most studies of wildlife-domestic animal interfaces have focused on livestock and little is known about the wildlife-companion animal interface. Here, we investigated the prevalence and phylogenetic relatedness of extended-spectrum cephalosporin-resistant (ESC-R) Escherichia coli from raccoons ( Procyon lotor ) and domestic dogs ( Canis lupus familiaris ) in the metropolitan area of Chicago, IL, USA. To assess the potential importance of spatial overlap with dogs, we explored whether raccoons sampled at public parks (i.e., parks where people and dogs could enter) differed in prevalence and phylogenetic relatedness of ESC-R E. coli to raccoons sampled at private parks (i.e., parks where people and dogs could not enter). Raccoons had a significantly higher prevalence of ESC-R E. coli (56.9%) than dogs (16.5%). However, the richness of ESC-R E. coli did not vary by host species. Further, core single-nucleotide polymorphism (SNP)-based phylogenetic analyses revealed that isolates did not cluster by host species, and in some cases displayed a high degree of similarity (i.e., differed by less than 20 core SNPs). Spatial overlap analyses revealed that ESC-R E. coli were more likely to be isolated from raccoons at public parks than raccoons at private parks, but only for parks located in suburban areas of Chicago, not urban areas. That said, ESC-R E. coli isolated from raccoons did not genetically cluster by park of origin. Our findings suggest that domestic dogs and urban/suburban raccoons can have a diverse range of ARB, some of which display a high degree of genetic relatedness (i.e., differ by less than 20 core SNPs). Given the differences in prevalence, domestic dogs are unlikely to be an important source of exposure for mesocarnivores in urbanized areas. IMPORTANCE Antimicrobial-resistant bacteria (ARB) have been detected in numerous wildlife species across the globe, which may have important implications for human and animal health. Wildlife can be exposed to ARB via numerous pathways, including via spatial overlap with domestic animals. However, the interface with domestic animals has mostly been explored for livestock and little is known about the interface between wild animals and companion animals. Our work suggests that urban and suburban wildlife can have similar ARB to local domestic dogs, but local dogs are unlikely to be a direct source of exposure for urban-adapted wildlife. This finding is important because it underscores the need to incorporate wildlife into antimicrobial resistance surveillance efforts, and to investigate whether certain urban wildlife species could act as additional epidemiological pathways of exposure for companion animals, and indirectly for humans. 

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3. A predicted deleterious allele of the essential meiosis gene MND1, present in ~ 3% of East Asians, does not disrupt reproduction in mice

   https://doi.org/10.1093/molehr/gaz048  

   Tran, Tina N. ; Martinez, Julianna ; Schimenti, John C. ( August 2019 , Molecular Human Reproduction)

   Infertility is a major health problem affecting ~15% of couples worldwide. Except for cases involving readily detectable chromosome aberrations, confident identification of a causative genetic defect is problematic. Despite the advent of genome sequencing for diagnostic purposes, the preponderance of segregating genetic variants complicates identification of culprit genetic alleles or mutations. Many algorithms have been developed to predict the effects of ‘variants of unknown significance’, typically single nucleotide polymorphisms (SNPs), but these predictions are not sufficiently accurate for clinical action. As part of a project to identify population variants that impact fertility, we have been generating clustered regularly interspaced short palindromic repeats-Cas9 edited mouse models of suspect SNPs in genes that are known to be required for fertility in mice. Here, we present data on a non-synonymous (amino acid altering) SNP (rs140107488) in the meiosis gene Mnd1, which is predicted bioinformatically to be deleterious to protein function. We report that when modeled in mice, this allele (MND1K85M), which is present at an allele frequency of ~ 3% in East Asians, has no discernable effect upon fertility, fecundity or gametogenesis, although it may cause sex skewing of progeny from homozygous males. In sum, assuming the mouse model accurately reflects the impact of this variant in humans, rs140107488 appears to be a benign allele that can be eliminated or de-prioritized in clinical genomic analyses of infertility patients.

    

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4. The genome of the black-footed cat: Revealing a rich natural history and urgent conservation priorities for small felids

   https://doi.org/10.1073/pnas.2310763120  

   Yuan, Jiaqing ; Kitchener, Andrew C. ; Lackey, Laurie Bingaman ; Sun, Ting ; Jiangzuo, Qigao ; Tuohetahong, Yilamujiang ; Zhao, Le ; Yang, Peng ; Wang, Guiqiang ; Huang, Chen ; et al ( January 2024 , Proceedings of the National Academy of Sciences)

   Habitat degradation and loss of genetic diversity are common threats faced by almost all of today’s wild cats. Big cats, such as tigers and lions, are of great concern and have received considerable conservation attention through policies and international actions. However, knowledge of and conservation actions for small wild cats are lagging considerably behind. The black-footed cat,Felis nigripes, one of the smallest felid species, is experiencing increasing threats with a rapid reduction in population size. However, there is a lack of genetic information to assist in developing effective conservation actions. A de novo assembly of a high-quality chromosome-level reference genome of the black-footed cat was made, and comparative genomics and population genomics analyses were carried out. These analyses revealed that the most significant genetic changes in the evolution of the black-footed cat are the rapid evolution of sensory and metabolic-related genes, reflecting genetic adaptations to its characteristic nocturnal hunting and a high metabolic rate. Genomes of the black-footed cat exhibit a high level of inbreeding, especially for signals of recent inbreeding events, which suggest that they may have experienced severe genetic isolation caused by habitat fragmentation. More importantly, inbreeding associated with two deleterious mutated genes may exacerbate the risk of amyloidosis, the dominant disease that causes mortality of about 70% of captive individuals. Our research provides comprehensive documentation of the evolutionary history of the black-footed cat and suggests that there is an urgent need to investigate genomic variations of small felids worldwide to support effective conservation actions.

    

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5. Germline landscape of RPA1, RPA2 and RPA3 variants in pediatric malignancies: identification of RPA1 as a novel cancer predisposition candidate gene

   https://doi.org/10.3389/fonc.2023.1229507  

   Sharma, Richa ; Oak, Ninad ; Chen, Wenan ; Gogal, Rose ; Kirschner, Martin ; Beier, Fabian ; Schnieders, Michael J. ; Spies, Maria ; Nichols, Kim E. ; Wlodarski, Marcin ( October 2023 , Frontiers in Oncology)

   Replication Protein A (RPA) is single-strand DNA binding protein that plays a key role in the replication and repair of DNA. RPA is a heterotrimer made of 3 subunits – RPA1, RPA2, and RPA3. Germline pathogenic variants affectingRPA1were recently described in patients with Telomere Biology Disorders (TBD), also known as dyskeratosis congenita or short telomere syndrome. Premature telomere shortening is a hallmark of TBD and results in bone marrow failure and predisposition to hematologic malignancies. Building on the finding that somatic mutations in RPA subunit genes occur in ~1% of cancers, we hypothesized that germline RPA alterations might be enriched in human cancers. Because germlineRPA1mutations are linked to early onset TBD with predisposition to myelodysplastic syndromes, we interrogated pediatric cancer cohorts to define the prevalence and spectrum of rare/novel and putative damaging germlineRPA1,RPA2, andRPA3variants. In this study of 5,993 children with cancer, 75 (1.25%) harbored heterozygous rare (non-cancer population allele frequency (AF) < 0.1%) variants in the RPA heterotrimer genes, of which 51 cases (0.85%) had ultra-rare (AF < 0.005%) or novel variants. Compared with Genome Aggregation Database (gnomAD) non-cancer controls, there was significant enrichment of ultra-rare and novelRPA1, but notRPA2orRPA3, germline variants in our cohort (adjusted p-value < 0.05). Taken together, these findings suggest that germline putative damaging variants affectingRPA1are found in excess in children with cancer, warranting further investigation into the functional role of these variants in oncogenesis.

    

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