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1.
BMC Genomics ; 23(1): 413, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35650521

RESUMO

BACKGROUND: Despite sexual development being ubiquitous to vertebrates, the molecular mechanisms underpinning this fundamental transition remain largely undocumented in many organisms. We designed a time course experiment that successfully sampled the period when Atlantic salmon commence their trajectory towards sexual maturation. RESULTS: Through deep RNA sequencing, we discovered key genes and pathways associated with maturation in the pituitary-ovarian axis. Analyzing DNA methylomes revealed a bias towards hypermethylation in ovary that implicated maturation-related genes. Co-analysis of DNA methylome and gene expression changes revealed chromatin remodeling genes and key transcription factors were both significantly hypermethylated and upregulated in the ovary during the onset of maturation. We also observed changes in chromatin state landscapes that were strongly correlated with fundamental remodeling of gene expression in liver. Finally, a multiomic integrated analysis revealed regulatory networks and identified hub genes including TRIM25 gene (encoding the estrogen-responsive finger protein) as a putative key regulator in the pituitary that underwent a 60-fold change in connectivity during the transition to maturation. CONCLUSION: The study successfully documented transcriptome and epigenome changes that involved key genes and pathways acting in the pituitary - ovarian axis. Using a Systems Biology approach, we identified hub genes and their associated networks deemed crucial for onset of maturation. The results provide a comprehensive view of the spatiotemporal changes involved in a complex trait and opens the door to future efforts aiming to manipulate puberty in an economically important aquaculture species.


Assuntos
Epigenoma , Transcriptoma , Animais , Feminino , Ovário/metabolismo , Análise de Sequência de RNA/métodos , Maturidade Sexual/genética
2.
Nat Commun ; 11(1): 2815, 2020 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-32499537

RESUMO

Understanding the genetic changes underlying phenotypic variation in sheep (Ovis aries) may facilitate our efforts towards further improvement. Here, we report the deep resequencing of 248 sheep including the wild ancestor (O. orientalis), landraces, and improved breeds. We explored the sheep variome and selection signatures. We detected genomic regions harboring genes associated with distinct morphological and agronomic traits, which may be past and potential future targets of domestication, breeding, and selection. Furthermore, we found non-synonymous mutations in a set of plausible candidate genes and significant differences in their allele frequency distributions across breeds. We identified PDGFD as a likely causal gene for fat deposition in the tails of sheep through transcriptome, RT-PCR, qPCR, and Western blot analyses. Our results provide insights into the demographic history of sheep and a valuable genomic resource for future genetic studies and improved genome-assisted breeding of sheep and other domestic animals.


Assuntos
Criação de Animais Domésticos/métodos , Animais Selvagens/genética , Fator de Crescimento Derivado de Plaquetas/metabolismo , Carneiro Doméstico/genética , Alelos , Animais , Cruzamento , Feminino , Frequência do Gene , Variação Genética , Genética , Genômica , Genótipo , Sequenciamento de Nucleotídeos em Larga Escala , Desequilíbrio de Ligação , Mutação , Fenótipo , Polimorfismo de Nucleotídeo Único , Seleção Genética , Análise de Sequência de DNA , Ovinos , Especificidade da Espécie , Sequenciamento Completo do Genoma
3.
Front Genet ; 11: 264, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32318091

RESUMO

The introduction of wild Atlantic salmon into captivity, and their subsequent artificial selection for production traits, has caused phenotypic differences between domesticated fish and their wild counterparts. Identification of regions of the genome underling these changes offers the promise of characterizing the early biological consequences of domestication. In the current study, we sequenced a population of farmed European Atlantic salmon and compared the observed patterns of SNP variation to those found in conspecific wild populations. This identified 139 genomic regions that contained significantly elevated SNP homozygosity in farmed fish when compared to their wild counterparts. The most extreme was adjacent to versican, a gene involved in control of neural crest cell migration. To control for false positive signals, a second and independent dataset of farmed and wild European Atlantic salmon was assessed using the same methodology. A total of 81 outlier regions detected in the first dataset showed significantly reduced homozygosity within the second one, strongly suggesting the genomic regions identified are enriched for true selection sweeps. Examination of the associated genes identified a number previously characterized as targets of selection in other domestic species and that have roles in development, behavior and olfactory system. These include arcvf, sema6, errb4, id2-like, and 6n1-like genes. Finally, we searched for evidence of parallel sweeps using a farmed population of North American origin. This failed to detect a convincing overlap to the putative sweeps present in European populations, suggesting the factors that drive patterns of variation under domestication and early artificial selection were largely independent. This is the first analysis on domestication of aquaculture species exploiting whole-genome sequence data and resulted in the identification of sweeps common to multiple independent populations of farmed European Atlantic salmon.

4.
BMC Genomics ; 20(1): 139, 2019 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-30770720

RESUMO

BACKGROUND: A key developmental transformation in the life of all vertebrates is the transition to sexual maturity, whereby individuals are capable of reproducing for the first time. In the farming of Atlantic salmon, early maturation prior to harvest size has serious negative production impacts. RESULTS: We report genome wide association studies (GWAS) using fish measured for sexual maturation in freshwater or the marine environment. Genotypic data from a custom 50 K single nucleotide polymorphism (SNP) array was used to identify 13 significantly associated SNP for freshwater maturation with the most strongly associated on chromosomes 10 and 11. A higher number of associations (48) were detected for marine maturation, and the two peak loci were found to be the same for both traits. The number and broad distribution of GWAS hits confirmed a highly polygenetic nature, and GWAS performed separately within males and females revealed sex specific genetic behaviour for loci co-located with positional candidate genes phosphatidylinositol-binding clathrin assembly protein-like (picalm) and membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2 (magi2). CONCLUSIONS: The results extend earlier work and have implications for future applied breeding strategies to delay maturation in this important aquaculture species.


Assuntos
Pesqueiros , Herança Multifatorial , Salmo salar/genética , Maturidade Sexual/genética , Maturidade Sexual/fisiologia , Animais , Sequência de Bases , Cruzamento , Bases de Dados Genéticas , Feminino , Água Doce , Expressão Gênica , Frequência do Gene , Variação Genética , Estudo de Associação Genômica Ampla , Genótipo , Guanilato Quinases/genética , Masculino , Proteínas Monoméricas de Montagem de Clatrina/genética , Polimorfismo de Nucleotídeo Único , Água do Mar , Fatores Sexuais , Tasmânia , Sequenciamento Completo do Genoma
5.
Front Genet ; 9: 369, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30271423

RESUMO

The availability of a reference genome assembly for Atlantic salmon, Salmo salar, SNP genotyping platforms and low cost sequencing are enhancing the understanding of both life history and production-related traits in this important commercial species. We collected and analyzed transcriptomes from selected tissues of Atlantic salmon to inform future functional and comparative genomics studies. Messenger RNA (mRNA) was isolated from pituitary gland, brain, ovary, and liver before Illumina sequencing produced a total of 640 million 150-bp paired-end reads. Following read mapping, feature counting, and normalization, cluster analysis identified genes highly expressed in a tissue-specific manner. We identified a cluster of 508 tissue specific genes for pituitary gland, 3395 for brain, 2939 for ovary, and 539 for liver. Functional profiling identified gene clusters describing the unique functions of each tissue. Moreover, highly-expressed transcription factors (TFs) present in each tissue-specific gene cluster were identified. TFs belonging to homeobox and bhlh families were identified for pituitary gland, pou and zf-c2h2 families for brain, arid, and zf-c2h2 for ovary and rxr-like family for liver. The data and analysis presented are relevant to the emerging Functional Annotation of All Salmonid Genomes (FAASG) initiative that is seeking to develop a detailed understanding of both salmonid evolution and the genomic elements that drive gene expression and regulation.

6.
Genomics ; 110(3): 143-148, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-28917637

RESUMO

Copy number variation (CNV) represents a major source of genomic variation. We investigated the diversity of CNV distribution using SNP array data collected from a comprehensive collection of geographically dispersed sheep breeds. We identified 24,558 putative CNVs, which can be merged into 619 CNV regions, spanning 197Mb of total length and corresponding to ~6.9% of the sheep genome. Our results reveal a population differentiation in CNV between different geographical areas, including Africa, America, Asia, Southwestern Asia, Central Europe, Northern Europe and Southwestern Europe. We observed clear distinctions in CNV prevalence between diverse groups, possibly reflecting the population history of different sheep breeds. We sought to determine the gene content of CNV, and found several important CNV-overlapping genes (BTG3, PTGS1 and PSPH) which were involved in fetal muscle development, prostaglandin (PG) synthesis, and bone color. Our study generates a comprehensive CNV map, which may contribute to genome annotation in sheep.


Assuntos
Variações do Número de Cópias de DNA , Carneiro Doméstico/genética , Animais , Cruzamento , Cromossomos de Mamíferos , Genômica , Análise de Sequência com Séries de Oligonucleotídeos , Polimorfismo de Nucleotídeo Único
7.
BMC Genomics ; 18(1): 484, 2017 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-28655320

RESUMO

We describe an emerging initiative - the 'Functional Annotation of All Salmonid Genomes' (FAASG), which will leverage the extensive trait diversity that has evolved since a whole genome duplication event in the salmonid ancestor, to develop an integrative understanding of the functional genomic basis of phenotypic variation. The outcomes of FAASG will have diverse applications, ranging from improved understanding of genome evolution, to improving the efficiency and sustainability of aquaculture production, supporting the future of fundamental and applied research in an iconic fish lineage of major societal importance.


Assuntos
Aquicultura , Conservação dos Recursos Naturais , Genômica , Internacionalidade , Anotação de Sequência Molecular , Salmonidae/genética , Animais , Evolução Molecular , Genômica/economia , Genômica/normas , Fenótipo , Filogenia
8.
BMC Genomics ; 18(1): 229, 2017 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-28288562

RESUMO

BACKGROUND: The detection of signatures of selection has the potential to elucidate the identities of genes and mutations associated with phenotypic traits important for livestock species. It is also very relevant to investigate the levels of genetic diversity of a population, as genetic diversity represents the raw material essential for breeding and has practical implications for implementation of genomic selection. A total of 1151 animals from nine goat populations selected for different breeding goals and genotyped with the Illumina Goat 50K single nucleotide polymorphisms (SNP) Beadchip were included in this investigation. RESULTS: The proportion of polymorphic SNPs ranged from 0.902 (Nubian) to 0.995 (Rangeland). The overall mean HO and HE was 0.374 ± 0.021 and 0.369 ± 0.023, respectively. The average pairwise genetic distance (D) ranged from 0.263 (Toggenburg) to 0.323 (Rangeland). The overall average for the inbreeding measures FEH, FVR, FLEUT, FROH and FPED was 0.129, -0.012, -0.010, 0.038 and 0.030, respectively. Several regions located on 19 chromosomes were potentially under selection in at least one of the goat breeds. The genomic population tree constructed using all SNPs differentiated breeds based on selection purpose, while genomic population tree built using only SNPs in the most significant region showed a great differentiation between LaMancha and the other breeds. We hypothesized that this region is related to ear morphogenesis. Furthermore, we identified genes potentially related to reproduction traits, adult body mass, efficiency of food conversion, abdominal fat deposition, conformation traits, liver fat metabolism, milk fatty acids, somatic cells score, milk protein, thermo-tolerance and ear morphogenesis. CONCLUSIONS: In general, moderate to high levels of genetic variability were observed for all the breeds and a characterization of runs of homozygosity gave insights into the breeds' development history. The information reported here will be useful for the implementation of genomic selection and other genomic studies in goats. We also identified various genome regions under positive selection using smoothed FST and hapFLK statistics and suggested genes, which are potentially under selection. These results can now provide a foundation to formulate biological hypotheses related to selection processes in goats.


Assuntos
Variação Genética , Genoma , Cabras/genética , Animais , Orelha/anatomia & histologia , Orelha/fisiologia , Frequência do Gene , Estudo de Associação Genômica Ampla , Genótipo , Heterozigoto , Homozigoto , Fenótipo , Polimorfismo de Nucleotídeo Único , Seleção Genética
9.
BMC Genomics ; 17: 441, 2016 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-27277319

RESUMO

BACKGROUND: Copy number variants (CNVs) are a type of polymorphism found to underlie phenotypic variation, both in humans and livestock. Most surveys of CNV in livestock have been conducted in the cattle genome, and often utilise only a single approach for the detection of copy number differences. Here we performed a study of CNV in sheep, using multiple methods to identify and characterise copy number changes. Comprehensive information from small pedigrees (trios) was collected using multiple platforms (array CGH, SNP chip and whole genome sequence data), with these data then analysed via multiple approaches to identify and verify CNVs. RESULTS: In total, 3,488 autosomal CNV regions (CNVRs) were identified in this study, which substantially builds on an initial survey of the sheep genome that identified 135 CNVRs. The average length of the identified CNVRs was 19 kb (range of 1 kb to 3.6 Mb), with shorter CNVRs being more frequent than longer CNVRs. The total length of all CNVRs was 67.6Mbps, which equates to 2.7 % of the sheep autosomes. For individuals this value ranged from 0.24 to 0.55 %, and the majority of CNVRs were identified in single animals. Rather than being uniformly distributed throughout the genome, CNVRs tended to be clustered. Application of three independent approaches for CNVR detection facilitated a comparison of validation rates. CNVs identified on the Roche-NimbleGen 2.1M CGH array generally had low validation rates with lower density arrays, while whole genome sequence data had the highest validation rate (>60 %). CONCLUSIONS: This study represents the first comprehensive survey of the distribution, prevalence and characteristics of CNVR in sheep. Multiple approaches were used to detect CNV regions and it appears that the best method for verifying CNVR on a large scale involves using a combination of detection methodologies. The characteristics of the 3,488 autosomal CNV regions identified in this study are comparable to other CNV regions reported in the literature and provide a valuable and sizeable addition to the small subset of published sheep CNVs.


Assuntos
Variações do Número de Cópias de DNA , Genoma , Genômica , Ovinos/genética , Animais , Cromossomos de Mamíferos , Hibridização Genômica Comparativa , Genômica/métodos , Sequenciamento de Nucleotídeos em Larga Escala , Polimorfismo de Nucleotídeo Único , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
10.
Sci Rep ; 6: 26770, 2016 05 27.
Artigo em Inglês | MEDLINE | ID: mdl-27230812

RESUMO

Tibetan sheep have lived on the Tibetan Plateau for thousands of years; however, the process and consequences of adaptation to this extreme environment have not been elucidated for important livestock such as sheep. Here, seven sheep breeds, representing both highland and lowland breeds from different areas of China, were genotyped for a genome-wide collection of single-nucleotide polymorphisms (SNPs). The FST and XP-EHH approaches were used to identify regions harbouring local positive selection between these highland and lowland breeds, and 236 genes were identified. We detected selection events spanning genes involved in angiogenesis, energy production and erythropoiesis. In particular, several candidate genes were associated with high-altitude hypoxia, including EPAS1, CRYAA, LONP1, NF1, DPP4, SOD1, PPARG and SOCS2. EPAS1 plays a crucial role in hypoxia adaption; therefore, we investigated the exon sequences of EPAS1 and identified 12 mutations. Analysis of the relationship between blood-related phenotypes and EPAS1 genotypes in additional highland sheep revealed that a homozygous mutation at a relatively conserved site in the EPAS1 3' untranslated region was associated with increased mean corpuscular haemoglobin concentration and mean corpuscular volume. Taken together, our results provide evidence of the genetic diversity of highland sheep and indicate potential high-altitude hypoxia adaptation mechanisms, including the role of EPAS1 in adaptation.


Assuntos
Aclimatação , Altitude , Ovinos/genética , Animais , Mapeamento Cromossômico , Feminino , Genoma , Genótipo , Masculino , Filogeografia , Polimorfismo de Nucleotídeo Único , Seleção Genética
11.
Anim Genet ; 47(2): 258-62, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26767438

RESUMO

Phenotypic variability in horn characteristics, such as their size, number and shape, offers the opportunity to elucidate the molecular basis of horn development. The objective of this study was to map the genetic determinant controlling the production of four horns in two breeds, Jacob sheep and Navajo-Churro, and examine whether an eyelid abnormality occurring in the same populations is related. Genome-wide association mapping was performed using 125 animals from the two breeds that contain two- and four-horned individuals. A case-control design analysis of 570 712 SNPs genotyped with the ovine HD SNP Beadchip revealed a strong association signal on sheep chromosome 2. The 10 most strongly associated SNPs were all located in a region spanning Mb positions 131.9-132.6, indicating the genetic architecture underpinning the production of four horns is likely to involve a single gene. The closest genes to the most strongly associated marker (OAR2_132568092) were MTX2 and the HOXD cluster, located approximately 93 Kb and 251 Kb upstream respectively. The occurrence of an eyelid malformation across both breeds was restricted to polled animals and those carrying more than two horns. This suggests the eyelid abnormality may be associated with departures from the normal developmental production of two-horned animals and that the two conditions are developmentally linked. This study demonstrated the presence of separate loci responsible for the polled and four-horned phenotypes in sheep and advanced our understanding of the complexity that underpins horn morphology in ruminants.


Assuntos
Estudos de Associação Genética , Loci Gênicos , Cornos/crescimento & desenvolvimento , Polimorfismo de Nucleotídeo Único , Ovinos/genética , Animais , Cruzamento , Estudos de Casos e Controles , Mapeamento Cromossômico , Pálpebras/anormalidades , Feminino , Marcadores Genéticos , Genótipo , Masculino , Fenótipo
12.
Genet Sel Evol ; 47: 78, 2015 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-26464167

RESUMO

BACKGROUND: Genetic relatedness is currently estimated by a combination of traditional pedigree-based approaches (i.e. numerator relationship matrices, NRM) and, given the recent availability of molecular information, using marker genotypes (via genomic relationship matrices, GRM). To date, GRM are computed by genome-wide pair-wise SNP (single nucleotide polymorphism) correlations. RESULTS: We describe a new estimate of genetic relatedness using the concept of normalised compression distance (NCD) that is borrowed from Information Theory. Analogous to GRM, the resultant compression relationship matrix (CRM) exploits numerical patterns in genome-wide allele order and proportion, which are known to vary systematically with relatedness. We explored properties of the CRM in two industry cattle datasets by analysing the genetic basis of yearling weight, a phenotype of moderate heritability. In both Brahman (Bos indicus) and Tropical Composite (Bos taurus by Bos indicus) populations, the clustering inferred by NCD was comparable to that based on SNP correlations using standard principal component analysis approaches. One of the versions of the CRM modestly increased the amount of explained genetic variance, slightly reduced the 'missing heritability' and tended to improve the prediction accuracy of breeding values in both populations when compared to both NRM and GRM. Finally, a sliding window-based application of the compression approach on these populations identified genomic regions influenced by introgression of taurine haplotypes. CONCLUSIONS: For these two bovine populations, CRM reduced the missing heritability and increased the amount of explained genetic variation for a moderately heritable complex trait. Given that NCD can sensitively discriminate closely related individuals, we foresee CRM having possible value for estimating breeding values in highly inbred populations.


Assuntos
Cruzamento , Modelos Genéticos , Linhagem , Algoritmos , Alelos , Animais , Simulação por Computador , Variação Genética , Estudo de Associação Genômica Ampla , Genômica/métodos , Genótipo , Polimorfismo de Nucleotídeo Único , Reprodutibilidade dos Testes
13.
BMC Genomics ; 16: 431, 2015 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-26044654

RESUMO

BACKGROUND: Domestic goats (Capra hircus) have been selected to play an essential role in agricultural production systems, since being domesticated from their wild progenitor, bezoar (Capra aegagrus). A detailed understanding of the genetic consequences imparted by the domestication process remains a key goal of evolutionary genomics. RESULTS: We constructed the reference genome of bezoar and sequenced representative breeds of domestic goats to search for genomic changes that likely have accompanied goat domestication and breed formation. Thirteen copy number variation genes associated with coat color were identified in domestic goats, among which ASIP gene duplication contributes to the generation of light coat-color phenotype in domestic goats. Analysis of rapidly evolving genes identified genic changes underlying behavior-related traits, immune response and production-related traits. CONCLUSION: Based on the comparison studies of copy number variation genes and rapidly evolving genes between wild and domestic goat, our findings and methodology shed light on the genetic mechanism of animal domestication and will facilitate future goat breeding.


Assuntos
Genoma , Cabras/genética , Sequência de Aminoácidos , Animais , Animais Domésticos/genética , Animais Selvagens/genética , Evolução Biológica , Cruzamento , DNA/análise , DNA/isolamento & purificação , Variações do Número de Cópias de DNA , Variação Genética , Sistema Imunitário/metabolismo , Masculino , Dados de Sequência Molecular , Proteínas Proteolipídicas Associadas a Linfócitos e Mielina/classificação , Proteínas Proteolipídicas Associadas a Linfócitos e Mielina/genética , Sistema Nervoso/metabolismo , Filogenia , Estrutura Terciária de Proteína , Receptor de Colecistocinina A/química , Receptor de Colecistocinina A/genética , Receptor de Colecistocinina A/metabolismo , Alinhamento de Sequência
14.
BMC Genet ; 16: 67, 2015 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-26108536

RESUMO

BACKGROUND: Basic understanding of linkage disequilibrium (LD) and population structure, as well as the consistency of gametic phase across breeds is crucial for genome-wide association studies and successful implementation of genomic selection. However, it is still limited in goats. Therefore, the objectives of this research were: (i) to estimate genome-wide levels of LD in goat breeds using data generated with the Illumina Goat SNP50 BeadChip; (ii) to study the consistency of gametic phase across breeds in order to evaluate the possible use of a multi-breed training population for genomic selection and (iii) develop insights concerning the population history of goat breeds. RESULTS: Average r(2) between adjacent SNP pairs ranged from 0.28 to 0.11 for Boer and Rangeland populations. At the average distance between adjacent SNPs in the current 50 k SNP panel (~0.06 Mb), the breeds LaMancha, Nubian, Toggenburg and Boer exceeded or approached the level of linkage disequilibrium that is useful (r(2) > 0.2) for genomic predictions. In all breeds LD decayed rapidly with increasing inter-marker distance. The estimated correlations for all the breed pairs, except Canadian and Australian Boer populations, were lower than 0.70 for all marker distances greater than 0.02 Mb. These results are not high enough to encourage the pooling of breeds in a single training population for genomic selection. The admixture analysis shows that some breeds have distinct genotypes based on SNP50 genotypes, such as the Boer, Cashmere and Nubian populations. The other groups share higher genome proportions with each other, indicating higher admixture and a more diverse genetic composition. CONCLUSIONS: This work presents results of a diverse collection of breeds, which are of great interest for the implementation of genomic selection in goats. The LD results indicate that, with a large enough training population, genomic selection could potentially be implemented within breed with the current 50 k panel, but some breeds might benefit from a denser panel. For multi-breed genomic evaluation, a denser SNP panel also seems to be required.


Assuntos
Cabras/genética , Desequilíbrio de Ligação , Animais , Austrália , Evolução Biológica , Cruzamento , Canadá , Frequência do Gene , Ligação Genética , Estudo de Associação Genômica Ampla , Genômica , Técnicas de Genotipagem , Células Germinativas/metabolismo , Polimorfismo de Nucleotídeo Único , Densidade Demográfica
16.
Mol Ecol Resour ; 15(4): 723-36, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25388640

RESUMO

Single nucleotide polymorphisms (SNPs) have become the marker of choice for genetic studies in organisms of conservation, commercial or biological interest. Most SNP discovery projects in nonmodel organisms apply a strategy for identifying putative SNPs based on filtering rules that account for random sequencing errors. Here, we analyse data used to develop 4723 novel SNPs for the commercially important deep-sea fish, orange roughy (Hoplostethus atlanticus), to assess the impact of not accounting for systematic sequencing errors when filtering identified polymorphisms when discovering SNPs. We used SAMtools to identify polymorphisms in a velvet assembly of genomic DNA sequence data from seven individuals. The resulting set of polymorphisms were filtered to minimize 'bycatch'-polymorphisms caused by sequencing or assembly error. An Illumina Infinium SNP chip was used to genotype a final set of 7714 polymorphisms across 1734 individuals. Five predictors were examined for their effect on the probability of obtaining an assayable SNP: depth of coverage, number of reads that support a variant, polymorphism type (e.g. A/C), strand-bias and Illumina SNP probe design score. Our results indicate that filtering out systematic sequencing errors could substantially improve the efficiency of SNP discovery. We show that BLASTX can be used as an efficient tool to identify single-copy genomic regions in the absence of a reference genome. The results have implications for research aiming to identify assayable SNPs and build SNP genotyping assays for nonmodel organisms.


Assuntos
Técnicas de Genotipagem/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Polimorfismo de Nucleotídeo Único , Vertebrados/classificação , Vertebrados/genética , Animais , Biologia Computacional/métodos
17.
Genome ; 57(8): 433-7, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25372788

RESUMO

Domestic animals represent an extremely useful model for linking genotypic and phenotypic variation. One approach involves identifying allele frequency differences between populations, using F(ST), to detect selective sweeps. While simple to calculate, FST may generate false positives due to aspects of population history. This prompted the development of hapFLK, a metric that measures haplotype differentiation while accounting for the genetic relationship between populations. The focus of this paper was to apply hapFLK in sheep with available SNP50 genotypes. The hapFLK approach identified a known selective sweep on chromosome 10 with high precision. Further, five regions were identified centered on genes with strong evidence for positive selection (COL1A2, NCAPG, LCORL, and RXFP2). Estimation of global F(ST) revealed many more genomic regions, providing empirical data in support of published simulation-based results concerning elevated type I error associated with F(ST) when it is being used to characterize sweep regions. The findings, while conducted using sheep SNP data, are likely to be applicable across those domestic animal species that have undergone artificial selection for desirable phenotypic traits.


Assuntos
Variação Genética , Genética Populacional/métodos , Haplótipos/genética , Modelos Genéticos , Seleção Genética/genética , Ovinos/genética , Software , Animais , Genótipo , Polimorfismo de Nucleotídeo Único/genética
18.
Mol Biol Evol ; 31(12): 3324-43, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25249477

RESUMO

Following domestication, sheep (Ovis aries) have become essential farmed animals across the world through adaptation to a diverse range of environments and varied production systems. Climate-mediated selective pressure has shaped phenotypic variation and has left genetic "footprints" in the genome of breeds raised in different agroecological zones. Unlike numerous studies that have searched for evidence of selection using only population genetics data, here, we conducted an integrated coanalysis of environmental data with single nucleotide polymorphism (SNP) variation. By examining 49,034 SNPs from 32 old, autochthonous sheep breeds that are adapted to a spectrum of different regional climates, we identified 230 SNPs with evidence for selection that is likely due to climate-mediated pressure. Among them, 189 (82%) showed significant correlation (P ≤ 0.05) between allele frequency and climatic variables in a larger set of native populations from a worldwide range of geographic areas and climates. Gene ontology analysis of genes colocated with significant SNPs identified 17 candidates related to GTPase regulator and peptide receptor activities in the biological processes of energy metabolism and endocrine and autoimmune regulation. We also observed high linkage disequilibrium and significant extended haplotype homozygosity for the core haplotype TBC1D12-CH1 of TBC1D12. The global frequency distribution of the core haplotype and allele OAR22_18929579-A showed an apparent geographic pattern and significant (P ≤ 0.05) correlations with climatic variation. Our results imply that adaptations to local climates have shaped the spatial distribution of some variants that are candidates to underpin adaptive variation in sheep.


Assuntos
Polimorfismo de Nucleotídeo Único , Carneiro Doméstico/genética , Aclimatação/genética , Animais , Cruzamento , Clima , Evolução Molecular , Frequência do Gene , Ontologia Genética , Genes , Haplótipos , Desequilíbrio de Ligação , Modelos Genéticos , Seleção Genética , Especificidade da Espécie
19.
Anim Genet ; 45(5): 754-7, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25040320

RESUMO

The extent of linkage disequilibrium (LD) between genetic loci has implications for both association studies and the accuracy of genomic prediction. To characterise the persistence of LD in diverse sheep breeds, two SNP genotyping platforms were used. First, existing SNP genotypes from 63 breeds obtained using the ovine SNP50 BeadChip (49,034 loci) were used to estimate LD decay in populations with contrasting levels of genetic diversity. Given the paucity of marker pairs separated by short physical distances on the SNP50 BeadChip, genotyping was subsequently performed for four breeds using the recently developed ovine HD BeadChip that assays approximately 600,000 SNPs with an average genomic spacing of 5 kb. This facilitated a highly accurate estimate of LD over short genomic distances (<30 kb) and revealed LD varies considerably between sheep breeds. Further, sheep appear to contain generally lower levels of LD than do other domestic species, likely a reflection of aspects of their past population history.


Assuntos
Desequilíbrio de Ligação , Polimorfismo de Nucleotídeo Único , Carneiro Doméstico/genética , Animais , Variação Genética , Genética Populacional , Análise de Sequência com Séries de Oligonucleotídeos
20.
PLoS One ; 9(4): e94851, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24740156

RESUMO

DNA-based parentage determination accelerates genetic improvement in sheep by increasing pedigree accuracy. Single nucleotide polymorphism (SNP) markers can be used for determining parentage and to provide unique molecular identifiers for tracing sheep products to their source. However, the utility of a particular "parentage SNP" varies by breed depending on its minor allele frequency (MAF) and its sequence context. Our aims were to identify parentage SNPs with exceptional qualities for use in globally diverse breeds and to develop a subset for use in North American sheep. Starting with genotypes from 2,915 sheep and 74 breed groups provided by the International Sheep Genomics Consortium (ISGC), we analyzed 47,693 autosomal SNPs by multiple criteria and selected 163 with desirable properties for parentage testing. On average, each of the 163 SNPs was highly informative (MAF≥0.3) in 48±5 breed groups. Nearby polymorphisms that could otherwise confound genetic testing were identified by whole genome and Sanger sequencing of 166 sheep from 54 breed groups. A genetic test with 109 of the 163 parentage SNPs was developed for matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry. The scoring rates and accuracies for these 109 SNPs were greater than 99% in a panel of North American sheep. In a blinded set of 96 families (sire, dam, and non-identical twin lambs), each parent of every lamb was identified without using the other parent's genotype. In 74 ISGC breed groups, the median estimates for probability of a coincidental match between two animals (PI), and the fraction of potential adults excluded from parentage (PE) were 1.1×10(-39) and 0.999987, respectively, for the 109 SNPs combined. The availability of a well-characterized set of 163 parentage SNPs facilitates the development of high-throughput genetic technologies for implementing accurate and economical parentage testing and traceability in many of the world's sheep breeds.


Assuntos
Cruzamento/métodos , Linhagem , Polimorfismo de Nucleotídeo Único , Ovinos/genética , Animais , Feminino , Frequência do Gene , Testes Genéticos/métodos , Genótipo , Masculino , Reprodutibilidade dos Testes , Análise de Sequência de DNA , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
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