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The diversity in genome resources is fundamental to designing genomic strategies for local breed improvement and utilisation. These resources also support gene discovery and enhance our understanding of the mechanisms of resilience with applications beyond local breeds. Here, we report the genome sequences of 555 cattle (208 of which comprise new data) and high-density (HD) array genotyping of 1,082 samples (537 new samples) from indigenous African cattle populations. The new sequences have an average genome coverage of ~30X, three times higher than the average (~10X) of the over 300 sequences already in the public domain. Following variant quality checks, we identified approximately 32.3 million sequence variants and 661,943 HD autosomal variants mapped to the Bos taurus reference genome (ARS-UCD1.2). The new datasets were generated as part of the Centre for Tropical Livestock Genetics and Health (CTLGH) Genomic Reference Resource for African Cattle (GRRFAC) initiative, which aspires to facilitate the generation of this livestock resource and hopes for its utilisation for complete indigenous breed characterisation and sustainable global livestock improvement.
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Genoma , Bovinos/genética , Animais , Genômica , África , Cruzamento , Variação GenéticaRESUMO
Anthropological and biophysical processes have shaped livestock genomes over Millenia and can explain their current geographic distribution and genetic divergence. We analyzed 57 Ethiopian indigenous domestic goat genomes alongside 67 equivalents of east, west, and north-west African, European, South Asian, Middle East, and wild Bezoar goats. Cluster, ADMIXTURE (K = 4) and phylogenetic analysis revealed four genetic groups comprising African, European, South Asian, and wild Bezoar goats. The Middle Eastern goats had an admixed genome of these four genetic groups. At K = 5, the West African Dwarf and Moroccan goats were separated from East African goats demonstrating a likely historical legacy of goat arrival and dispersal into Africa via the coastal Mediterranean Sea and the Horn of Africa. FST, XP-EHH, and Hp analysis revealed signatures of selection in Ethiopian goats overlaying genes for thermo-sensitivity, oxidative stress response, high-altitude hypoxic adaptation, reproductive fitness, pathogen defence, immunity, pigmentation, DNA repair, modulation of renal function and integrated fluid and electrolyte homeostasis. Notable examples include TRPV1 (a nociception gene); PTPMT1 (a critical hypoxia survival gene); RETREG (a regulator of reticulophagy during starvation), and WNK4 (a molecular switch for osmoregulation). These results suggest that human-mediated translocations and adaptation to contrasting environments are shaping indigenous African goat genomes.
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Genoma , Cabras , Filogenia , Animais , Cabras/genética , Etiópia , Estresse Fisiológico/genética , Variação GenéticaRESUMO
Domestic goats are distributed worldwide, with approximately 35% of the one billion world goat population occurring in Africa. Ethiopia has 52.5 million goats, ~99.9% of which are considered indigenous landraces deriving from animals introduced to the Horn of Africa in the distant past by nomadic herders. They have continued to be managed by smallholder farmers and semi-mobile pastoralists throughout the region. We report here 57 goat genomes from 12 Ethiopian goat populations sampled from different agro-climates. The data were generated through sequencing DNA samples on the Illumina NovaSeq 6000 platform at a mean depth of 9.71x and 150 bp pair-end reads. In total, ~2 terabytes of raw data were generated, and 99.8% of the clean reads mapped successfully against the goat reference genome assembly at a coverage of 99.6%. About 24.76 million SNPs were generated. These SNPs can be used to study the population structure and genome dynamics of goats at the country, regional, and global levels to shed light on the species' evolutionary trajectory.
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Genoma , Cabras , Animais , Evolução Biológica , DNA , Etiópia , Cabras/genéticaRESUMO
BACKGROUND: The genomes of indigenous African cattle are composed of components with Middle Eastern (taurine) and South Asian (indicine) origins, providing a valuable model to study hybridization and to identify genetic barriers to gene flow. In this study, we analysed indigenous African cattle breeds as models of hybrid zones, considering taurine and indicine samples as ancestors. In a genomic cline analysis of whole-genome sequence data, we considered over 8 million variants from 144 animals, which allows for fine-mapping of potential genomic incompatibilities at high resolution across the genome. RESULTS: We identified several thousand variants that had significantly steep clines ('SCV') across the whole genome, indicating restricted introgression. Some of the SCV were clustered into extended regions, with the longest on chromosome 7, spanning 725 kb and including 27 genes. We found that variants with a high phenotypic impact (e.g. indels, intra-genic and missense variants) likely represent greater genetic barriers to gene flow. Furthermore, our findings provide evidence that a large proportion of breed differentiation in African cattle could be linked to genomic incompatibilities and reproductive isolation. Functional evaluation of genes with SCV suggest that mitonuclear incompatibilities and genes associated with fitness (e.g. resistance to paratuberculosis) could account for restricted gene flow in indigenous African cattle. CONCLUSIONS: To our knowledge, this is the first time genomic cline analysis has been applied to identify restricted introgression in the genomes of indigenous African cattle and the results provide extended insights into mechanisms (e.g. genomic incompatibilities) contributing to hybrid differentiation. These results have important implications for our understanding of genetic incompatibilities and reproductive isolation and provide important insights into the impact of cross-breeding cattle with the aim of producing offspring that are both hardy and productive.
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Genoma , Genômica , Animais , Bovinos/genética , Hibridização Genética , Fluxo Gênico , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Indicine cattle, also referred to as zebu (Bos taurus indicus), play a central role in pastoral communities across a wide range of agro-ecosystems, from extremely hot semiarid regions to hot humid tropical regions. However, their adaptive genetic changes following their dispersal into East Asia from the Indian subcontinent have remained poorly documented. Here, we characterize their global genetic diversity using high-quality whole-genome sequencing data from 354 indicine cattle of 57 breeds/populations, including major indicine phylogeographic groups worldwide. We reveal their probable migration into East Asia was along a coastal route rather than inland routes and we detected introgression from other bovine species. Genomic regions carrying morphology-, immune-, and heat-tolerance-related genes underwent divergent selection according to Asian agro-ecologies. We identify distinct sets of loci that contain promising candidate variants for adaptation to hot semi-arid and hot humid tropical ecosystems. Our results indicate that the rapid and successful adaptation of East Asian indicine cattle to hot humid environments was promoted by localized introgression from banteng and/or gaur. Our findings provide insights into the history and environmental adaptation of indicine cattle.
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Evolução Biológica , Ecossistema , Animais , Bovinos , Alelos , Variação Genética , Sequenciamento Completo do Genoma , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Environmental adaptation traits of indigenous African cattle are increasingly being investigated to respond to the need for sustainable livestock production in the context of unpredictable climatic changes. Several studies have highlighted genomic regions under positive selection probably associated with adaptation to environmental challenges (e.g. heat stress, trypanosomiasis, tick and tick-borne diseases). However, little attention has focused on pinpointing the candidate causative variant(s) controlling the traits. This review compiled information from 22 studies on signatures of positive selection in indigenous African cattle breeds to identify regions under positive selection. We highlight some key candidate genome regions and genes of relevance to the challenges of living in extreme environments (high temperature, high altitude, high infectious disease prevalence). They include candidate genes involved in biological pathways relating to innate and adaptive immunity (e.g. BoLAs, SPAG11, IL1RL2 and GFI1B), heat stress (e.g. HSPs, SOD1 and PRLH) and hypoxia responses (e.g. BDNF and INPP4A). Notably, the highest numbers of candidate regions are found on BTA3, BTA5 and BTA7. They overlap with genes playing roles in several biological functions and pathways. These include but are not limited to growth and feed intake, cell stability, protein stability and sweat gland development. This review may further guide targeted genome studies aiming to assess the importance of candidate causative mutations, within regulatory and protein-coding genome regions, to further understand the biological mechanisms underlying African cattle's unique adaption.
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Genoma , Genômica , Bovinos/genética , Animais , Resposta ao Choque Térmico , Seleção Genética , Polimorfismo de Nucleotídeo ÚnicoRESUMO
A structural variant (SV) in the agouti signaling protein gene (ASIP), namely ASIP-SV1, has been found to strongly correlate with the darkness of hair coat in specific regions of the body of bulls from the zebu (Bos indicus) Nellore breed. Here we visually analyzed the whole-genome sequence of zebu and taurine (Bos taurus) cattle to elucidate the extent of spread of ASIP-SV1 in different cattle populations. Of 216 sequences analyzed, 63 zebu (45.9%) and five taurine (6.3%) animals had at least one copy of ASIP-SV1. Four of the taurine animals presenting the SV were Romagnola cattle, a breed with history of zebu introgression. The remaining taurine animal was a Simmental, a breed frequently used in crossbreeding. These data provide evidence that ASIP-SV1 is commonly found in zebu populations, in addition to taurine animals with zebu admixture.
Assuntos
Cabelo , Hibridização Genética , Bovinos/genética , Masculino , Animais , Escuridão , AlelosRESUMO
The mountainous areas of Ethiopia represent one of the most extreme environmental challenges in Africa faced by humans and other inhabitants. Selection for high-altitude adaptation is expected to have imprinted the genomes of livestock living in these areas. Here we assess the genomic signatures of positive selection for high altitude adaptation in three cattle populations from the Ethiopian mountainous areas (Semien, Choke, and Bale mountains) compared to three Ethiopian lowland cattle populations (Afar, Ogaden, and Boran), using whole-genome resequencing and three genome scan approaches for signature of selection (iHS, XP-CLR, and PBS). We identified several candidate selection signature regions and several high-altitude adaptation genes. These include genes such as ITPR2, MB, and ARNT previously reported in the human population inhabiting the Ethiopian highlands. Furthermore, we present evidence of strong selection and high divergence between Ethiopian high- and low-altitude cattle populations at three new candidate genes (CLCA2, SLC26A2, and CBFA2T3), putatively linked to high-altitude adaptation in cattle. Our findings provide possible examples of convergent selection between cattle and humans as well as unique African cattle signature to the challenges of living in the Ethiopian mountainous regions.
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BACKGROUND: In cattle, genome-wide association studies (GWAS) have largely focused on European or Asian breeds, using genotyping arrays that were primarily designed for European cattle. Because there is growing interest in performing GWAS in African breeds, we have assessed the performance of 23 commercial bovine genotyping arrays for capturing the diversity across African breeds and performing imputation. We used 409 whole-genome sequences (WGS) spanning global cattle breeds, and a real cohort of 2481 individuals (including African breeds) that were genotyped with the Illumina high-density (HD) array and the GeneSeek bovine 50 k array. RESULTS: We found that commercially available arrays were not effective in capturing variants that segregate among African indicine animals. Only 6% of these variants in high linkage disequilibrium (LD) (r2 > 0.8) were on the best performing arrays, which contrasts with the 17% and 25% in African and European taurine cattle, respectively. However, imputation from available HD arrays can successfully capture most variants (accuracies up to 0.93), mainly when using a global, not continent-specific, reference panel, which partially reflects the unusually high levels of admixture on the continent. When considering functional variants, the GGPF250 array performed best for tagging WGS variants and imputation. Finally, we show that imputation from low-density arrays can perform almost as well as HD arrays, if a two-stage imputation approach is adopted, i.e. first imputing to HD and then to WGS, which can potentially reduce the costs of GWAS. CONCLUSIONS: Our results show that the choice of an array should be based on a balance between the objective of the study and the breed/population considered, with the HD and BOS1 arrays being the best choice for both taurine and indicine breeds when performing GWAS, and the GGPF250 being preferable for fine-mapping studies. Moreover, our results suggest that there is no advantage to using the indicus-specific arrays for indicus breeds, regardless of the objective. Finally, we show that using a reference panel that better represents global bovine diversity improves imputation accuracy, particularly for non-European taurine populations.
Assuntos
Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo Único , Animais , Bovinos/genética , Genótipo , Desequilíbrio de LigaçãoRESUMO
BACKGROUND: Indigenous Sudanese cattle are mainly indicine/zebu (humped) type. They thrive in the harshest dryland environments characterised by high temperatures, long seasonal dry periods, nutritional shortages, and vector disease challenges. Here, we sequenced 60 indigenous Sudanese cattle from six indigenous breeds and analysed the data using three genomic scan approaches to unravel cattle adaptation to the African dryland region. RESULTS: We identified a set of gene-rich selective sweep regions, detected mostly on chromosomes 5, 7 and 19, shared across African and Gir zebu. These include genes involved in immune response, body size and conformation, and heat stress response. We also identified selective sweep regions unique to Sudanese zebu. Of these, a 250 kb selective sweep on chromosome 16 spans seven genes, including PLCH2, PEX10, PRKCZ, and SKI, which are involved in alternative adaptive metabolic strategies of insulin signalling, glucose homeostasis, and fat metabolism. CONCLUSIONS: Our results suggest that environmental adaptation may involve recent and ancient selection at gene-rich regions, which might be under a common regulatory genetic control, in zebu cattle.
Assuntos
Genoma , Polimorfismo de Nucleotídeo Único , Adaptação Fisiológica/genética , Animais , Sequência de Bases , Bovinos/genética , Genômica/métodosRESUMO
BACKGROUND: Cattle are considered to be the most desirable livestock by small scale farmers. In Africa, although comprehensive genomic studies have been carried out on cattle, the genetic variations in indigenous cattle from Nigeria have not been fully explored. In this study, genome-wide analysis based on genotyping-by-sequencing (GBS) of 193 Nigerian cattle was used to reveal new insights on the history of West African cattle and their adaptation to the tropical African environment, particularly in sub-Saharan region. RESULTS: The GBS data were evaluated against whole-genome sequencing (WGS) data and high rate of variant concordance between the two platforms was evident with high correlated genetic distance matrices genotyped by both methods suggestive of the reliability of GBS applicability in population genetics. The genetic structure of Nigerian cattle was observed to be homogenous and unique from other African cattle populations. Selection analysis for the genomic regions harboring imprints of adaptation revealed genes associated with immune responses, growth and reproduction, efficiency of feeds utilization, and heat tolerance. Our findings depict potential convergent adaptation between African cattle, dogs and humans with adaptive genes SPRY2 and ITGB1BP1 possibly involved in common physiological activities. CONCLUSION: The study presents unique genetic patterns of Nigerian cattle which provide new insights on the history of cattle in West Africa based on their population structure and the possibility of parallel adaptation between African cattle, dogs and humans in Africa which require further investigations.
Assuntos
Genoma , Polimorfismo de Nucleotídeo Único , Animais , Bovinos/genética , Genética Populacional , Nigéria , Reprodutibilidade dos Testes , Seleção GenéticaRESUMO
BACKGROUND: CNV comprises a large proportion in cattle genome and is associated with various traits. However, there were few population-scale comparison studies on cattle CNV. RESULTS: Here, autosome-wide CNVs were called by read depth of NGS alignment result and copy number variation regions (CNVRs) defined from 102 Eurasian taurine (EAT) of 14 breeds, 28 Asian indicine (ASI) of 6 breeds, 22 African taurine (AFT) of 2 breeds, and 184 African humped cattle (AFH) of 17 breeds. The copy number of every CNVRs were compared between populations and CNVRs with population differentiated copy numbers were sorted out using the pairwise statistics VST and Kruskal-Wallis test. Three hundred sixty-two of CNVRs were significantly differentiated in both statistics and 313 genes were located on the population differentiated CNVRs. CONCLUSION: For some of these genes, the averages of copy numbers were also different between populations and these may be candidate genes under selection. These include olfactory receptors, pathogen-resistance, parasite-resistance, heat tolerance and productivity related genes. Furthermore, breed- and individual-level comparison was performed using the presence or copy number of the autosomal CNVRs. Our findings were based on identification of CNVs from short Illumina reads of 336 individuals and 39 breeds, which to our knowledge is the largest dataset for this type of analysis and revealed important CNVs that may play a role in cattle adaption to various environments.
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Variações do Número de Cópias de DNA , Genoma , Animais , Bovinos/genética , Sequenciamento de Nucleotídeos em Larga Escala , Fenótipo , Polimorfismo de Nucleotídeo ÚnicoRESUMO
The African cattle provide unique genetic resources shaped up by both diverse tropical environmental conditions and human activities, the assessment of their genetic diversity will shade light on the mechanism of their remarkable adaptive capacities. We therefore analyzed the genetic diversity of cattle samples from Nigeria using both maternal and paternal DNA markers. Nigerian cattle can be assigned to 80 haplotypes based on the mitochondrial DNA (mtDNA) D-loop sequences and haplotype diversity was 0.985 + 0.005. The network showed two major matrilineal clustering: the dominant cluster constituting the Nigerian cattle together with other African cattle while the other clustered Eurasian cattle. Paternal analysis indicates only zebu haplogroup in Nigerian cattle with high genetic diversity 1.000 ± 0.016 compared to other cattle. There was no signal of maternal genetic structure in Nigerian cattle population, which may suggest an extensive genetic intermixing within the country. The absence of Bos indicus maternal signal in Nigerian cattle is attributable to vulnerability bottleneck of mtDNA lineages and concordance with the view of male zebu genetic introgression in African cattle. Our study shades light on the current genetic diversity in Nigerian cattle and population history in West Africa.
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Cattle pastoralism plays a central role in human livelihood in Africa. However, the genetic history of its success remains unknown. Here, through whole-genome sequence analysis of 172 indigenous African cattle from 16 breeds representative of the main cattle groups, we identify a major taurine × indicine cattle admixture event dated to circa 750-1,050 yr ago, which has shaped the genome of today's cattle in the Horn of Africa. We identify 16 loci linked to African environmental adaptations across crossbred animals showing an excess of taurine or indicine ancestry. These include immune-, heat-tolerance- and reproduction-related genes. Moreover, we identify one highly divergent locus in African taurine cattle, which is putatively linked to trypanotolerance and present in crossbred cattle living in trypanosomosis-infested areas. Our findings indicate that a combination of past taurine and recent indicine admixture-derived genetic resources is at the root of the present success of African pastoralism.
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Adaptação Fisiológica/genética , Cruzamento , Bovinos , Genoma , Sequenciamento Completo do Genoma , África , Alelos , Animais , Bovinos/genética , Genótipo , Temperatura Alta/efeitos adversos , Mosaicismo , Polimorfismo de Nucleotídeo Único , Reprodução/genética , Sequenciamento Completo do Genoma/veterináriaRESUMO
Like most West African Bos taurus, the shorthorn Muturu is under threat of replacement or crossbreeding with zebu. Their populations are now reduced to a few hundred breeding individuals and they are considered endangered. So far, the genetic variation and genetic basis of the trypanotolerant Muturu environmental adaptation have not been assessed. Here, we present genome-wide candidate positive selection signatures in Muturu following within-population iHS and between population Rsb signatures of selection analysis. We compared the results in Muturu with the ones obtained in N'Dama, a West African longhorn trypanotolerant taurine, and in two European taurine (Holstein and Jersey). The results reveal candidate signatures of selection regions in Muturu including genes linked to the innate (e.g., TRIM10, TRIM15, TRIM40, and TRIM26) and the adaptive (e.g., JSP.1, BOLA-DQA2, BOLA-DQA5, BOLA-DRB3, and BLA-DQB) immune responses. The most significant regions are identified on BTA 23 at the bovine major histocompatibility complex (MHC) (iHS analysis) and on BTA 12 at genes including a heat tolerance gene (INTS6) (Rsb analysis). Other candidate selected regions include genes related to growth traits/stature (e.g., GHR and GHRHR), coat color (e.g., MITF and KIT), feed efficiency (e.g., ZRANB3 and MAP3K5) and reproduction (e.g., RFX2, SRY, LAP3, and GPX5). Genes under common signatures of selection regions with N'Dama, including for adaptive immunity and heat tolerance, suggest shared mechanisms of adaptation to environmental challenges for these two West African taurine cattle. Interestingly, out of the 242,910 SNPs identified within the candidate selected regions in Muturu, 917 are missense SNPs (0.4%), with an unequal distribution across 273 genes. Fifteen genes including RBBP8, NID1, TEX15, LAMA3, TRIM40, and OR12D3 comprise 220 missense variants, each between 11 and 32. Our results, while providing insights into the candidate genes under selection in Muturu, are paving the way to the identification of genes and their polymorphisms linked to the unique tropical adaptive traits of the West Africa taurine, including trypanotolerance.
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Navel injuries caused by friction against the pasture can promote infection, reproductive problems and costly treatments in beef cattle raised in extensive systems. A haplotype-based genome-wide association study (GWAS) was performed for visual scores of navel length at yearling in Nellore cattle (Bos indicus) using data from 2,016 animals and 503,088 single nucleotide polymorphism (SNP) markers. The strongest signal (p = 1.01 × 10-9) was found on chromosome 5 spanning positions 47.9-48.2 Mbp. This region contains introns 3 and 4 and exons 4 and 5 of the high mobility group AT-hook 2 gene (HMGA2). Further inspection of the region with whole genome sequence data of 21 Nellore bulls revealed correlations between counts of the significant haplotype and copy number gains of a â¼6.2 kbp segment of intron 3 of HMGA2. Analysis of genome sequences from five African B. indicus and four European Bos taurus breeds revealed that the copy number variant (CNV) is indicine-specific. This intronic CNV was then validated through quantitative polymerase chain reaction (qPCR) using Angus animals as copy neutral controls. Importantly, the CNV was not detectable by means of conventional SNP-based GWAS or SNP probe intensity analyses. Given that HMGA2 affects the expression of the insulin-like growth factor 2 gene (IGF2) together with the pleomorphic adenoma gene 1 (PLAG1), and that the latter has been repeatedly shown to be associated with quantitative traits of economic importance in cattle, these findings highlight the emerging role of variants impacting the insulin-like growth factor pathway to cattle breeding.
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The East African Shorthorn Zebu (EASZ) cattle are ancient hybrid between Asian zebu × African taurine cattle preferred by local farmers due to their adaptability to the African environment. The genetic controls of these adaptabilities are not clearly understood yet. Here, we genotyped 92 EASZ samples from Kenya (KEASZ) with more than 770,000 SNPs and sequenced the genome of a pool of 10 KEASZ. We observe an even admixed autosomal zebu × taurine genomic structure in the population. A total of 101 and 165 candidate regions of positive selection, based on genome-wide SNP analyses (meta-SS, Rsb, iHS, and ΔAF) and pooled heterozygosity (Hp) full genome sequence analysis, are identified, in which 35 regions are shared between them. A total of 142 functional variants, one novel, have been detected within these regions, in which 30 and 26 were classified as of zebu and African taurine origins, respectively. High density genome-wide SNP analysis of zebu × taurine admixed cattle populations from Uganda and Nigeria show that 25 of these regions are shared between KEASZ and Uganda cattle, and seven regions are shared across the KEASZ, Uganda, and Nigeria cattle. The identification of common candidate regions allows us to fine map 18 regions. These regions intersect with genes and QTL associated with reproduction and environmental stress (e.g., immunity and heat stress) suggesting that the genome of the zebu × taurine admixed cattle has been uniquely selected to maximize hybrid fitness both in terms of reproduction and survivability.