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1.
R Soc Open Sci ; 11(3): 231388, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38571912

RESUMO

Criollo cattle, the descendants of animals brought by Iberian colonists to the Americas, have been the subject of natural and human-mediated selection in novel tropical agroecological zones for centuries. Consequently, these breeds have evolved distinct characteristics such as resistance to diseases and exceptional heat tolerance. In addition to European taurine (Bos taurus) ancestry, it has been proposed that gene flow from African taurine and Asian indicine (Bos indicus) cattle has shaped the ancestry of Criollo cattle. In this study, we analysed Criollo breeds from Colombia and Venezuela using whole-genome sequencing (WGS) and single-nucleotide polymorphism (SNP) array data to examine population structure and admixture at high resolution. Analysis of genetic structure and ancestry components provided evidence for African taurine and Asian indicine admixture in Criollo cattle. In addition, using WGS data, we detected selection signatures associated with a myriad of adaptive traits, revealing genes linked to thermotolerance, reproduction, fertility, immunity and distinct coat and skin coloration traits. This study underscores the remarkable adaptability of Criollo cattle and highlights the genetic richness and potential of these breeds in the face of climate change, habitat flux and disease challenges. Further research is warranted to leverage these findings for more effective and sustainable cattle breeding programmes.

2.
Antiviral Res ; 221: 105793, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38184111

RESUMO

CD163 expressed on cell surface of porcine alveolar macrophages (PAMs) serves as a cellular entry receptor for porcine reproductive and respiratory syndrome virus (PRRSV). The extracellular portion of CD163 contains nine scavenger receptor cysteine-rich (SRCR) and two proline-serine-threonine (PST) domains. Genomic editing of pigs to remove the entire CD163 or just the SRCR5 domain confers resistance to infection with both PRRSV-1 and PRRSV-2 viruses. By performing a mutational analysis of CD163, previous in vitro infection experiments showed resistance to PRRSV infection following deletion of exon 13 which encodes the first 12 amino acids of the 16 amino acid PSTII domain. These findings predicted that removal of exon 13 can be used as a strategy to produce gene-edited pigs fully resistant to PRRSV infection. In this study, to determine whether the deletion of exon 13 is sufficient to confer resistance of pigs to PRRSV infection, we produced pigs possessing a defined CD163 exon 13 deletion (ΔExon13 pigs) and evaluated their susceptibility to viral infection. Wild type (WT) and CD163 modified pigs, placed in the same room, were infected with PRRSV-2. The modified pigs remained PCR and serologically negative for PRRSV throughout the study; whereas the WT pigs supported PRRSV infection and showed PRRSV related pathology. Importantly, our data also suggested that removal of exon 13 did not affect the main physiological function associated with CD163 in vivo. These results demonstrate that a modification of CD163 through a precise deletion of exon 13 provides a strategy for protection against PRRSV infection.


Assuntos
Síndrome Respiratória e Reprodutiva Suína , Vírus da Síndrome Respiratória e Reprodutiva Suína , Suínos , Animais , Vírus da Síndrome Respiratória e Reprodutiva Suína/genética , Síndrome Respiratória e Reprodutiva Suína/genética , Macrófagos Alveolares , Edição de Genes/métodos , Éxons
3.
Front Genet ; 14: 1200770, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37745840

RESUMO

Introduction: The African Goat Improvement Network Image Collection Protocol (AGIN-ICP) is an accessible, easy to use, low-cost procedure to collect phenotypic data via digital images. The AGIN-ICP collects images to extract several phenotype measures including health status indicators (anemia status, age, and weight), body measurements, shapes, and coat color and pattern, from digital images taken with standard digital cameras or mobile devices. This strategy is to quickly survey, record, assess, analyze, and store these data for use in a wide variety of production and sampling conditions. Methods: The work was accomplished as part of the multinational African Goat Improvement Network (AGIN) collaborative and is presented here as a case study in the AGIN collaboration model and working directly with community-based breeding programs (CBBP). It was iteratively developed and tested over 3 years, in 12 countries with over 12,000 images taken. Results and discussion: The AGIN-ICP development is described, and field implementation and the quality of the resulting images for use in image analysis and phenotypic data extraction are iteratively assessed. Digital body measures were validated using the PreciseEdge Image Segmentation Algorithm (PE-ISA) and software showing strong manual to digital body measure Pearson correlation coefficients of height, length, and girth measures (0.931, 0.943, 0.893) respectively. It is critical to note that while none of the very detailed tasks in the AGIN-ICP described here is difficult, every single one of them is even easier to accidentally omit, and the impact of such a mistake could render a sample image, a sampling day's images, or even an entire sampling trip's images difficult or unusable for extracting digital phenotypes. Coupled with tissue sampling and genomic testing, it may be useful in the effort to identify and conserve important animal genetic resources and in CBBP genetic improvement programs by providing reliably measured phenotypes with modest cost. Potential users include farmers, animal husbandry officials, veterinarians, regional government or other public health officials, researchers, and others. Based on these results, a final AGIN-ICP is presented, optimizing the costs, ease, and speed of field implementation of the collection method without compromising the quality of the image data collection.

4.
Front Genet ; 14: 1183240, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37712066

RESUMO

The African Goat Improvement Network (AGIN) is a collaborative group of scientists focused on genetic improvement of goats in small holder communities across the African continent. The group emerged from a series of workshops focused on enhancing goat productivity and sustainability. Discussions began in 2011 at the inaugural workshop held in Nairobi, Kenya. The goals of this diverse group were to: improve indigenous goat production in Africa; characterize existing goat populations and to facilitate germplasm preservation where appropriate; and to genomic approaches to better understand adaptation. The long-term goal was to develop cost-effective strategies to apply genomics to improve productivity of small holder farmers without sacrificing adaptation. Genome-wide information on genetic variation enabled genetic diversity studies, facilitated improved germplasm preservation decisions, and provided information necessary to initiate large scale genetic improvement programs. These improvements were partially implemented through a series of community-based breeding programs that engaged and empowered local small farmers, especially women, to promote sustainability of the production system. As with many international collaborative efforts, the AGIN work serves as a platform for human capacity development. This paper chronicles the evolution of the collaborative approach leading to the current AGIN organization and describes how it builds capacity for sustained research and development long after the initial program funds are gone. It is unique in its effectiveness for simultaneous, multi-level capacity building for researchers, students, farmers and communities, and local and regional government officials. The positive impact of AGIN capacity building has been felt by participants from developing, as well as developed country partners.

6.
BMC Genomics ; 24(1): 313, 2023 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-37308830

RESUMO

BACKGROUND: Rewriting the genomes of living organisms has been a long-standing aim in the biological sciences. The revelation of the CRISPR/Cas9 technology has revolutionized the entire biological field. Since its emergence, this technology has been widely applied to induce gene knockouts, insertions, deletions, and base substitutions. However, the classical version of this system was imperfect for inducing or correcting desired mutations. A subsequent development generated more advanced classes, including cytosine and adenine base editors, which can be used to achieve single nucleotide substitutions. Nevertheless, these advanced systems still suffer from several limitations, such as the inability to edit loci without a suitable PAM sequence and to induce base transversions. On the other hand, the recently emerged prime editors (PEs) can achieve all possible single nucleotide substitutions as well as targeted insertions and deletions, which show promising potential to alter and correct the genomes of various organisms. Of note, the application of PE to edit livestock genomes has not been reported yet. RESULTS: In this study, using PE, we successfully generated sheep with two agriculturally significant mutations, including the fecundity-related FecBB p.Q249R and the tail length-related TBXT p.G112W. Additionally, we applied PE to generate porcine blastocysts with a biomedically relevant point mutation (KCNJ5 p.G151R) as a porcine model of human primary aldosteronism. CONCLUSIONS: Our study demonstrates the potential of the PE system to edit the genomes of large animals for the induction of economically desired mutations and for modeling human diseases. Although prime-edited sheep and porcine blastocysts could be generated, the editing frequencies are still unsatisfactory, highlighting the need for optimizations in the PE system for efficient generation of large animals with customized traits.


Assuntos
Blastocisto , Mutação Puntual , Humanos , Animais , Suínos , Ovinos , Mutação , Gado , Nucleotídeos , Canais de Potássio Corretores do Fluxo de Internalização Acoplados a Proteínas G
7.
PNAS Nexus ; 2(5): pgad125, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37181049

RESUMO

Bovine viral diarrhea virus (BVDV) is one of the most important viruses affecting the health and well-being of bovine species throughout the world. Here, we used CRISPR-mediated homology-directed repair and somatic cell nuclear transfer to produce a live calf with a six amino acid substitution in the BVDV binding domain of bovine CD46. The result was a gene-edited calf with dramatically reduced susceptibility to infection as measured by reduced clinical signs and the lack of viral infection in white blood cells. The edited calf has no off-target edits and appears normal and healthy at 20 months of age without obvious adverse effects from the on-target edit. This precision bred, proof-of-concept animal provides the first evidence that intentional genome alterations in the CD46 gene may reduce the burden of BVDV-associated diseases in cattle and is consistent with our stepwise, in vitro and ex vivo experiments with cell lines and matched fetal clones.

8.
Mol Biol Evol ; 39(12)2022 12 05.
Artigo em Inglês | MEDLINE | ID: mdl-36382357

RESUMO

Understanding the genetic mechanism of how animals adapt to extreme conditions is fundamental to determine the relationship between molecular evolution and changing environments. Goat is one of the first domesticated species and has evolved rapidly to adapt to diverse environments, including harsh high-altitude conditions with low temperature and poor oxygen supply but strong ultraviolet radiation. Here, we analyzed 331 genomes of domestic goats and wild caprid species living at varying altitudes (high > 3000 m above sea level and low < 1200 m), along with a reference-guided chromosome-scale assembly (contig-N50: 90.4 Mb) of a female Tibetan goat genome based on PacBio HiFi long reads, to dissect the genetic determinants underlying their adaptation to harsh conditions on the Qinghai-Tibetan Plateau (QTP). Population genomic analyses combined with genome-wide association studies (GWAS) revealed a genomic region harboring the 3'-phosphoadenosine 5'-phosphosulfate synthase 2 (PAPSS2) gene showing strong association with high-altitude adaptability (PGWAS = 3.62 × 10-25) in Tibetan goats. Transcriptomic data from 13 tissues revealed that PAPSS2 was implicated in hypoxia-related pathways in Tibetan goats. We further verified potential functional role of PAPSS2 in response to hypoxia in PAPSS2-deficient cells. Introgression analyses suggested that the PAPSS2 haplotype conferring the high-altitude adaptability in Tibetan goats originated from a recent hybridization between goats and a wild caprid species, the markhor (Capra falconeri). In conclusion, our results uncover a hitherto unknown contribution of PAPSS2 to high-altitude adaptability in Tibetan goats on QTP, following interspecific introgression and natural selection.


Assuntos
Estudo de Associação Genômica Ampla , Cabras , Animais , Cabras/genética , Raios Ultravioleta , Genômica
9.
PLoS One ; 17(10): e0275821, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36227957

RESUMO

Computer vision is a tool that could provide livestock producers with digital body measures and records that are important for animal health and production, namely body height and length, and chest girth. However, to build these tools, the scarcity of labeled training data sets with uniform images (pose, lighting) that also represent real-world livestock can be a challenge. Collecting images in a standard way, with manual image labeling is the gold standard to create such training data, but the time and cost can be prohibitive. We introduce the PreciseEdge image segmentation algorithm to address these issues by employing a standard image collection protocol with a semi-automated image labeling method, and a highly precise image segmentation for automated body measurement extraction directly from each image. These elements, from image collection to extraction are designed to work together to yield values highly correlated to real-world body measurements. PreciseEdge adds a brief preprocessing step inspired by chromakey to a modified GrabCut procedure to generate image masks for data extraction (body measurements) directly from the images. Three hundred RGB (red, green, blue) image samples were collected uniformly per the African Goat Improvement Network Image Collection Protocol (AGIN-ICP), which prescribes camera distance, poses, a blue backdrop, and a custom AGIN-ICP calibration sign. Images were taken in natural settings outdoors and in barns under high and low light, using a Ricoh digital camera producing JPG images (converted to PNG prior to processing). The rear and side AGIN-ICP poses were used for this study. PreciseEdge and GrabCut image segmentation methods were compared for differences in user input required to segment the images. The initial bounding box image output was captured for visual comparison. Automated digital body measurements extracted were compared to manual measures for each method. Both methods allow additional optional refinement (mouse strokes) to aid the segmentation algorithm. These optional mouse strokes were captured automatically and compared. Stroke count distributions for both methods were not normally distributed per Kolmogorov-Smirnov tests. Non-parametric Wilcoxon tests showed the distributions were different (p< 0.001) and the GrabCut stroke count was significantly higher (p = 5.115 e-49), with a mean of 577.08 (std 248.45) versus 221.57 (std 149.45) with PreciseEdge. Digital body measures were highly correlated to manual height, length, and girth measures, (0.931, 0.943, 0.893) for PreciseEdge and (0.936, 0. 944, 0.869) for GrabCut (Pearson correlation coefficient). PreciseEdge image segmentation allowed for masks yielding accurate digital body measurements highly correlated to manual, real-world measurements with over 38% less user input for an efficient, reliable, non-invasive alternative to livestock hand-held direct measuring tools.


Assuntos
Gado , Infecções Sexualmente Transmissíveis , Algoritmos , Animais , Processamento de Imagem Assistida por Computador/métodos , Camundongos
10.
iScience ; 25(7): 104672, 2022 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-35832892

RESUMO

The phenotypic diversity of African cattle reflects adaptation to a wide range of agroecological conditions, human-mediated selection preferences, and complex patterns of admixture between the humpless Bos taurus (taurine) and humped Bos indicus (zebu) subspecies, which diverged 150-500 thousand years ago. Despite extensive admixture, all African cattle possess taurine mitochondrial haplotypes, even populations with significant zebu biparental and male uniparental nuclear ancestry. This has been interpreted as the result of human-mediated dispersal ultimately stemming from zebu bulls imported from South Asia during the last three millennia. Here, we assess whether ancestry at mitochondrially targeted nuclear genes in African admixed cattle is impacted by mitonuclear functional interactions. Using high-density SNP data, we find evidence for mitonuclear coevolution across hybrid African cattle populations with a significant increase of taurine ancestry at mitochondrially targeted nuclear genes. Our results, therefore, support the hypothesis of incompatibility between the taurine mitochondrial genome and the zebu nuclear genome.

11.
Front Genet ; 13: 866176, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35591856

RESUMO

Estimated breeding values (EBV) for fecal egg counts (FEC) at 42-90 days of age (WFEC) and 91-150 days of age (PFEC) for 84 progeny-tested Katahdin sires were used to identify associations of deregressed EBV with single-nucleotide polymorphisms (SNP) using 388,000 SNP with minor-allele frequencies ≥0.10 on an Illumina high-density ovine array. Associations between markers and FEC EBV were initially quantified by single-SNP linear regression. Effects of linkage disequilibrium (LD) were minimized by assigning SNP to 2,535 consecutive 1-Mb bins and focusing on the effect of the most significant SNP in each bin. Bonferroni correction was used to define bin-based (BB) genome- and chromosome-wide significance. Six bins on chromosome 5 achieved BB genome-wide significance for PFEC EBV, and three of those SNP achieved chromosome-wide significance after Bonferroni correction based on the 14,530 total SNP on chromosome 5. These bins were nested within 12 consecutive bins between 59 and 71 Mb on chromosome 5 that reached BB chromosome-wide significance. The largest SNP effects were at 63, 67, and 70 Mb, with LD among these SNP of r 2 ≤ 0.2. Regional heritability mapping (RHM) was then used to evaluate the ability of different genomic regions to account for additive variance in FEC EBV. Chromosome-level RHM indicated that one 500-SNP window between 65.9 and 69.9 Mb accounted for significant variation in PFEC EBV. Five additional 500-SNP windows between 59.3 and 71.6 Mb reached suggestive (p < 0.10) significance for PFEC EBV. Although previous studies rarely identified markers for parasite resistance on chromosome 5, the IL12B gene at 68.5 Mb codes for the p40 subunit of both interleukins 12 and 23. Other immunoregulatory genes are also located in this region of chromosome 5, providing opportunity for additive or associative effects.

12.
BMC Genomics ; 23(1): 344, 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35508966

RESUMO

BACKGROUND: The gaur (Bos gaurus) is the largest extant wild bovine species, native to South and Southeast Asia, with unique traits, and is listed as vulnerable by the International Union for Conservation of Nature (IUCN). RESULTS: We report the first gaur reference genome and identify three biological pathways including lysozyme activity, proton transmembrane transporter activity, and oxygen transport with significant changes in gene copy number in gaur compared to other mammals. These may reflect adaptation to challenges related to climate and nutrition. Comparative analyses with domesticated indicine (Bos indicus) and taurine (Bos taurus) cattle revealed genomic signatures of artificial selection, including the expansion of sperm odorant receptor genes in domesticated cattle, which may have important implications for understanding selection for male fertility. CONCLUSIONS: Apart from aiding dissection of economically important traits, the gaur genome will also provide the foundation to conserve the species.


Assuntos
Receptores Odorantes , Animais , Bovinos/genética , Genoma , Genômica , Masculino , Mamíferos , Receptores Odorantes/genética , Espermatozoides , Glicoproteínas da Zona Pelúcida
13.
Animal ; 16(5): 100523, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35468510

RESUMO

The SLICK1 mutation in bovine PRLR (c.1382del; rs517047387) is a deletion mutation resulting in a protein with a truncated intracellular domain. Cattle carrying at least one allele have a phenotype characterized by a short hair coat (slick phenotype) and increased resistance to heat stress. Given the pleiotropic nature of prolactin, the mutation may affect other physiological characteristics. The liver is one organ that could potentially be affected because of the expression of PRLR. The mutation is a dominant allele, and heterozygous animals have a similar hair coat to that of animals homozygous for the mutation. Present objectives were to determine whether inheritance of the SLICK1 mutation affects liver gene expression and if animals homozygous for the SLICK1 allele differ from heterozygotes in liver gene expression and regulation of body temperature during heat stress. In one experiment, rectal and ruminal temperatures were less for Holstein heifers that were heterozygous for the SLICK1 allele compared with wildtype heifers. There were 71 differentially expressed genes in liver, with 13 upregulated and 58 downregulated in SLICK1 heterozygotes. Among the ontologies characteristic of differentially expressed genes were those related to immune function and fatty acid and amino acid metabolism. In a prospective cohort study conducted with adult Senepol cattle, body temperature and hepatic gene expression were compared between animals heterozygous or homozygous for the SLICK1 mutation. There were no differences in ruminal temperatures between genotypes, rectal temperature was higher in animals homozygous for the SLICK1 mutation, and there was only one gene in liver that was differentially expressed. It was concluded that inheritance of the SLICK1 allele can exert functional changes beyond those related to hair growth although changes in liver gene expression were not extensive. Results are also consistent with the SLICK1 allele being dominant because there were few differences in phenotype between animals inheriting one or two copies of the allele.


Assuntos
Doenças dos Bovinos , Transtornos de Estresse por Calor , Animais , Temperatura Corporal , Regulação da Temperatura Corporal/genética , Bovinos/genética , Doenças dos Bovinos/genética , Feminino , Expressão Gênica , Regulação da Expressão Gênica , Transtornos de Estresse por Calor/veterinária , Fígado , Mutação , Estudos Prospectivos
14.
Sci China Life Sci ; 65(2): 362-375, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34109474

RESUMO

Beef and mutton production has been aided by breeding to integrate allelic diversity for myostatin (MSTN), but a lack of diversity in the MSTN germplasm has limited similar advances in pig farming. Moreover, insurmountable challenges with congenital lameness and a dearth of data about the impacts of feed conversion, reproduction, and meat quality in MSTN-edited pigs have also currently blocked progress. Here, in a largest-to-date evaluation of multiple MSTN-edited pig populations, we demonstrated a practical alternative edit-site-based solution that overcomes the major production obstacle of hindlimb weakness. We also provide long-term and multidomain datasets for multiple breeds that illustrate how MSTN-editing can sustainably increase the yields of breed-specific lean meat and the levels of desirable lipids without deleteriously affecting feed-conversion rates or litter size. Apart from establishing a new benchmark for the data scale and quality of genome-edited animal production, our study specifically illustrates how gene-editing site selection profoundly impacts the phenotypic outcomes in diverse genetic backgrounds.


Assuntos
Edição de Genes/métodos , Coxeadura Animal/prevenção & controle , Miostatina/genética , Carne de Porco/análise , Doenças dos Suínos/prevenção & controle , Alelos , Fenômenos Fisiológicos da Nutrição Animal , Animais , Animais Geneticamente Modificados , Metabolismo Energético , Membro Posterior/fisiopatologia , Coxeadura Animal/genética , Coxeadura Animal/metabolismo , Especificidade da Espécie , Suínos/genética , Doenças dos Suínos/genética , Doenças dos Suínos/metabolismo , Termogênese
15.
Front Genet ; 13: 1078991, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36685939

RESUMO

Introduction: Most male pigs are surgically castrated to avoid puberty-derived boar taint and aggressiveness. However, this surgical intervention represents a welfare concern in swine production. Disrupting porcine KISS1 is hypothesized to delay or abolish puberty by inducing variable hypogonadotropism and thus preventing the need for castration. Methods: To test this hypothesis, we generated the first KISS1-edited large animal using CRISPR/Cas9-ribonucleoproteins and single-stranded donor oligonucleotides. The targeted region preceded the sequence encoding a conserved core motif of kisspeptin. Genome editors were intracytoplasmically injected into 684 swine zygotes and transferred to 19 hormonally synchronized surrogate sows. In nine litters, 49 American Yorkshire and 20 Duroc liveborn piglets were naturally farrowed. Results: Thirty-five of these pigs bore KISS1-disruptive alleles ranging in frequency from 5% to 97% and did not phenotypically differ from their wild-type counterparts. In contrast, four KISS1-edited pigs (two boars and two gilts) with disruptive allele frequencies of 96% and 100% demonstrated full hypogonadotropism, infantile reproductive tracts, and failed to reach sexual maturity. Change in body weight during development was unaffected by editing KISS1. Founder pigs partially carrying KISS1-disruptive alleles were bred resulting in a total of 53 KISS1 +/+, 60 KISS1 +/-, and 34 KISS1 -/- F1 liveborn piglets, confirming germline transmission. Discussion: Results demonstrate that a high proportion of KISS1 alleles in pigs must be disrupted before variation in gonadotropin secretion is observed, suggesting that even a small amount of kisspeptin ligand is sufficient to confer proper sexual development and puberty in pigs. Follow-on studies will evaluate fertility restoration in KISS1 KO breeding stock to fully realize the potential of KISS1 gene edits to eliminate the need for surgical castration.

16.
Viruses ; 13(11)2021 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-34834954

RESUMO

Bovine viral diarrhea virus's (BVDV) entry into bovine cells involves attachment of virions to cellular receptors, internalization, and pH-dependent fusion with endosomal membranes. The primary host receptor for BVDV is CD46; however, the complete set of host factors required for virus entry is unknown. The Madin-Darby bovine kidney (MDBK) cell line is susceptible to BVDV infection, while a derivative cell line (CRIB) is resistant at the level of virus entry. We performed complete genome sequencing of each to identify genomic variation underlying the resistant phenotype with the aim of identifying host factors essential for BVDV entry. Three large compound deletions in the BVDV-resistant CRIB cell line were identified and predicted to disrupt the function or expression of the genes PTPN12, GRID2, and RABGAP1L. However, CRISPR/Cas9 mediated knockout of these genes, individually or in combination, in the parental MDBK cell line did not impact virus entry or replication. Therefore, resistance to BVDV in the CRIB cell line is not due to the apparent spontaneous loss of PTPN12, GRID2, or RABGAP1L gene function. Identifying the functional cause of BVDV resistance in the CRIB cell line may require more detailed comparisons of the genomes and epigenomes.


Assuntos
Linhagem Celular , Vírus da Diarreia Viral Bovina/fisiologia , Deleção de Genes , Animais , Sistemas CRISPR-Cas , Diarreia/virologia , Cães , Proteínas Ativadoras de GTPase/genética , Técnicas de Inativação de Genes , Proteínas do Tecido Nervoso/genética , Proteína Tirosina Fosfatase não Receptora Tipo 12/genética , Receptores de Glutamato/genética , Internalização do Vírus , Replicação Viral , Sequenciamento Completo do Genoma
17.
Natl Sci Rev ; 8(8): nwab067, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34691713

RESUMO

Genetically modified food animals (GMFAs) are needed to address early the cumulative effects of livestock production on the environment, and to accommodate future food demands. In 2020 China and the USA, the world's two largest economies, embarked on regulatory reforms to boost the commercialization of such animals. However, gaining social acceptance of GMFAs for commercialization remains a global challenge. We propose a framework that focuses on social license for commercialization of GMFAs by defining four classes of improvement using precision genetics: (1) animals equivalent to natural variation to obtain the improved effect of cross-breeding (ENV); (2) animals with an inactivated gene that could occur via natural mutation (ENC-); (3) animals harboring a natural genetic sequence isolated from another species (ENC+); and (4) animals with synthetic sequences encoding novel genes (BNE). Our approach can guide regulators and the public to support orderly commercialization of GMFAs.

18.
Genet Sel Evol ; 53(1): 40, 2021 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-33910501

RESUMO

BACKGROUND: Nellore cattle (Bos indicus) are well-known for their adaptation to warm and humid environments. Hair length and coat color may impact heat tolerance. The Nellore breed has been strongly selected for white coat, but bulls generally exhibit darker hair ranging from light grey to black on the head, neck, hump, and knees. Given the potential contribution of coat color variation to the adaptation of cattle populations to tropical and sub-tropical environments, our aim was to map positional and functional candidate genetic variants associated with darkness of hair coat (DHC) in Nellore bulls. RESULTS: We performed a genome-wide association study (GWAS) for DHC using data from 432 Nellore bulls that were genotyped for more than 777 k single nucleotide polymorphism (SNP) markers. A single major association signal was detected in the vicinity of the agouti signaling protein gene (ASIP). The analysis of whole-genome sequence (WGS) data from 21 bulls revealed functional variants that are associated with DHC, including a structural rearrangement involving ASIP (ASIP-SV1). We further characterized this structural variant using Oxford Nanopore sequencing data from 13 Australian Brahman heifers, which share ancestry with Nellore cattle; we found that this variant originates from a 1155-bp deletion followed by an insertion of a transposable element of more than 150 bp that may impact the recruitment of ASIP non-coding exons. CONCLUSIONS: Our results indicate that the variant ASIP sequence causes darker coat pigmentation on specific parts of the body, most likely through a decreased expression of ASIP and consequently an increased production of eumelanin.


Assuntos
Proteína Agouti Sinalizadora/genética , Bovinos/genética , Pigmentação/genética , Polimorfismo Genético , Pelo Animal/metabolismo , Animais , Elementos de DNA Transponíveis , Mutação INDEL , Melaninas/genética , Melaninas/metabolismo
20.
BMC Genomics ; 21(1): 682, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33004001

RESUMO

BACKGROUND: Bos taurus and Bos indicus are two main sub-species of cattle. However, the differential copy number variations (CNVs) between them are not yet well studied. RESULTS: Based on the new high-quality cattle reference genome ARS-UCD1.2, we identified 13,234 non-redundant CNV regions (CNVRs) from 73 animals of 10 cattle breeds (4 Bos taurus and 6 Bos indicus), by integrating three detection strategies. While 6990 CNVRs (52.82%) were shared by Bos taurus and Bos indicus, large CNV differences were discovered between them and these differences could be used to successfully separate animals into two subspecies. We found that 2212 and 538 genes uniquely overlapped with either indicine-specific CNVRs and or taurine-specific CNVRs, respectively. Based on FST, we detected 16 candidate lineage-differential CNV segments (top 0.1%) under selection, which overlapped with eight genes (CTNNA1, ENSBTAG00000004415, PKN2, BMPER, PDE1C, DNAJC18, MUSK, and PLCXD3). Moreover, we obtained 1.74 Mbp indicine-specific sequences, which could only be mapped on the Bos indicus reference genome UOA_Brahman_1. We found these sequences and their associated genes were related to heat resistance, lipid and ATP metabolic process, and muscle development under selection. We further analyzed and validated the top significant lineage-differential CNV. This CNV overlapped genes related to muscle cell differentiation, which might be generated from a retropseudogene of CTH but was deleted along Bos indicus lineage. CONCLUSIONS: This study presents a genome wide CNV comparison between Bos taurus and Bos indicus. It supplied essential genome diversity information for understanding of adaptation and phenotype differences between the Bos taurus and Bos indicus populations.


Assuntos
Bovinos/genética , Variações do Número de Cópias de DNA , Filogenia , Animais , Bovinos/classificação , Evolução Molecular
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