A Novel Dynamic Impact Approach (DIA) for Functional Analysis of Time-Course Omics Studies: Validation Using the Bovine Mammary Transcriptome

The overrepresented approach (ORA) is the most widely-accepted method for functional analysis of microarray datasets. The ORA is computationally-efficient and robust; however, it suffers from the inability of comparing results from multiple gene lists particularly with time-course experiments or those involving multiple treatments. To overcome such limitation a novel method termed Dynamic Impact Approach (DIA) is proposed. The DIA provides an estimate of the biological impact of the experimental conditions and the direction of the impact. The impact is obtained by combining the proportion of differentially expressed genes (DEG) with the log2 mean fold change and mean –log P-value of genes associated with the biological term. The direction of the impact is calculated as the difference of the impact of up-regulated DEG and down-regulated DEG associated with the biological term. The DIA was validated using microarray data from a time-course experiment of bovine mammary gland across the lactation cycle. Several annotation databases were analyzed with DIA and compared to the same analysis performed by the ORA. The DIA highlighted that during lactation both BTA6 and BTA14 were the most impacted chromosomes; among Uniprot tissues those related with lactating mammary gland were the most positively-impacted; within KEGG pathways ‘Galactose metabolism’ and several metabolism categories related to lipid synthesis were among the most impacted and induced; within Gene Ontology “lactose biosynthesis” among Biological processes and “Lactose synthase activity” and “Stearoyl-CoA 9-desaturase activity” among Molecular processes were the most impacted and induced. With the exception of the terms ‘Milk’, ‘Milk protein’ and ‘Mammary gland’ among Uniprot tissues and SP_PIR_Keyword, the use of ORA failed to capture as significantly-enriched (i.e., biologically relevant) any term known to be associated with lactating mammary gland. Results indicate the DIA is a biologically-sound approach for analysis of time-course experiments. This tool represents an alternative to ORA for functional analysis

Old and New Stories: Revelations from Functional Analysis of the Bovine Mammary Transcriptome during the Lactation Cycle

The cow mammary transcriptome was explored at −30, −15, 1, 15, 30, 60, 120, 240, and 300 d relative to parturition. A total of 6,382 differentially expressed genes (DEG) at a false discovery rate ≤0.001 were found throughout lactation. The greatest number of DEG (>3,500 DEG) was observed at 60 and 120 d vs. −30 d with the largest change between consecutive time points observed at −15 vs. 1 d and 120 vs. 240 d. Functional analysis of microarray data was performed using the Dynamic Impact Approach (DIA). The DIA analysis of KEGG pathways uncovered as the most impacted and induced ‘Galactose metabolism’, ‘Glycosylphosphatidylinositol (GPI)-anchor biosynthesis’, and ‘PPAR signaling’; whereas, ‘Antigen processing and presentation’ was among the most inhibited. The integrated interpretation of the results suggested an overall increase in metabolism during lactation, particularly synthesis of carbohydrates and lipid. A marked degree of utilization of amino acids as energy source, an increase of protein export, and a decrease of the protein synthesis machinery as well cell cycle also were suggested by the DIA analysis. The DIA analysis of Gene Ontology and other databases uncovered an induction of Golgi apparatus and angiogenesis, and the inhibition of both immune cell activity/migration and chromosome modifications during lactation. All of the highly-impacted and activated functions during lactation were evidently activated at the onset of lactation and inhibited when milk production declined. The overall analysis indicated that the bovine mammary gland relies heavily on a coordinated transcriptional regulation to begin and end lactation. The functional analysis using DIA underscored the importance of genes associated with lactose synthesis, lipid metabolism, protein synthesis, Golgi, transport, cell cycle/death, epigenetic regulation, angiogenesis, and immune function during lactation

Integrating technologies for the sustainable control of gastrointestinal parasites in sheep : The Argentinean case

Gastrointestinal nematode infections in sheep are a major concern among breeders due to the economic losses they cause in terms of a reduction in both productivity and viability of animals. The situation worsens in face of the emergence of anthelmintic-resistant parasites. In this context, breeding and management practices aimed at an integrated control of parasites, such as raising parasiteresistant sheep, are required. This study focused on the genetic variation underlying parasite resistance in sheep, for potential use in breeding programmes. An artificial challenge with infectious H. contortus L3 was carried out in the northeast region of Argentina for more than 10 years in 1 072 Corriedale lambs with an average age of 5.6 months. Body weight, faecal egg count, packed cell volume, and FAMACHA© score were recorded at different time points post-challenge and their heritability and phenotypic and genetic correlations were estimated. Animals were genotyped on 173 single nucleotide polymorphisms belonging to 77 candidate genes for immune response. The results indicate that there is sufficient genetic variability for the four traits studied, which presented moderate heritabilities (in the range 0.29 to 0.44) and increased along the challenge period, with the exception of the hematocrit, which decreased. Association analyses identified seven markers associated with estimated breeding values for faecal egg count, located in genes involved in different stages of the pathogen-host interaction process. The information obtained supports the potential of markerassisted breeding schemes to enable profitable and sustainable sheep production.Instituto de GenéticaFil: Poli, Mario Andres. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Genética; ArgentinaFil: Poli, Mario Andres. Universidad del Salvador. Facultad de Ciencias Agrarias y Veterinaria; ArgentinaFil: Caffaro, Marí­a Eugenia. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Genética; ArgentinaFil: Cetra, Bibiana Maria. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Mercedes; ArgentinaFil: Raschia, Maria Agustina. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Genética; ArgentinaFil: Medus, Pablo Daniel. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Concepción del Uruguay; ArgentinaFil: Maizon, Daniel Omar. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Anguil; ArgentinaFil: Garcia Podesta, Mario. Joint FAO/IAEA Division of Nuclear Techniques in Food and Agriculture, International Atomic Energy Agency. Animal Production and Health Laboratory; AustriaFil: Donzelli, María Valeria. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Genética; ArgentinaFil: Bonelli, Rita. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Concepción del Uruguay; ArgentinaFil: Periasamy, Kathiravan. Joint FAO/IAEA Division of Nuclear Techniques in Food and Agriculture, International Atomic Energy Agency. Animal Production and Health Laboratory; Austri

Paternal Origins and Migratory Episodes of Domestic Sheep

The domestication and subsequent global dispersal of livestock are crucial events in human history, but the migratory episodes during the history of livestock remain poorly documented [1-3]. Here, we first developed a set of 493 novel ovine SNPs of the male-specific region of Y chromosome (MSY) by genome mapping. We then conducted a comprehensive genomic analysis of Y chromosome, mitochondrial DNA, and whole-genome sequence variations in a large number of 595 rams representing 118 domestic populations across the world. We detected four different paternal lineages of domestic sheep and resolved, at the global level, their paternal origins and differentiation. In Northern European breeds, several of which have retained primitive traits (e.g., a small body size and short or thin tails), and fat-tailed sheep, we found an overrepresentation of MSY lineages y-HC and y-HB, respectively. Using an approximate Bayesian computation approach, we reconstruct the demographic expansions associated with the segregation of primitive and fat-tailed phenotypes. These results together with archaeological evidence and historical data suggested the first expansion of early domestic hair sheep and the later expansion of fat-tailed sheep occurred ∼11,800-9,000 years BP and ∼5,300-1,700 years BP, respectively. These findings provide important insights into the history of migration and pastoralism of sheep across the Old World, which was associated with different breeding goals during the Neolithic agricultural revolution

Whole-genome resequencing of wild and domestic sheep identifies genes associated with morphological and agronomic traits

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

Whole-Genome Resequencing of Worldwide Wild and Domestic Sheep Elucidates Genetic Diversity, Introgression, and Agronomically Important Loci

Domestic sheep and their wild relatives harbor substantial genetic variants that can form the backbone of molecular breeding, but their genome landscapes remain understudied. Here, we present a comprehensive genome resource for wild ovine species, landraces and improved breeds of domestic sheep, comprising high-coverage (similar to 16.10x) whole genomes of 810 samples from 7 wild species and 158 diverse domestic populations. We detected, in total, similar to 121.2 million single nucleotide polymorphisms, similar to 61 million of which are novel. Some display significant (P < 0.001) differences in frequency between wild and domestic species, or are private to continent-wide or individual sheep populations. Retained or introgressed wild gene variants in domestic populations have contributed to local adaptation, such as the variation in the HBB associated with plateau adaptation. We identified novel and previously reported targets of selection on morphological and agronomic traits such as stature, horn, tail configuration, and wool fineness. We explored the genetic basis of wool fineness and unveiled a novel mutation (chr25: T7,068,586C) in the 3 '-UTR of IRF2BP2 as plausible causal variant for fleece fiber diameter. We reconstructed prehistorical migrations from the Near Eastern domestication center to South-and-Southeast Asia and found two main waves of migrations across the Eurasian Steppe and the Iranian Plateau in the Early and Late Bronze Ages. Our findings refine our understanding of genome variation as shaped by continental migrations, introgression, adaptation, and selection of sheep

Paternal origins and migratory episodes of domestic sheep.

The domestication and subsequent global dispersal of livestock are crucial events in human history, but the migratory episodes during the history of livestock remain poorly documented [1-3]. Here, we first developed a set of 493 novel ovine SNPs of the male-specific region of Y chromosome (MSY) by genome mapping. We then conducted a comprehensive genomic analysis of Y chromosome, mitochondrial DNA, and whole-genome sequence variations in a large number of 595 rams representing 118 domestic populations across the world. We detected four different paternal lineages of domestic sheep and resolved, at the global level, their paternal origins and differentiation. In Northern European breeds, several of which have retained primitive traits (e.g., a small body size and short or thin tails), and fat-tailed sheep, we found an overrepresentation of MSY lineages y-HC and y-HB, respectively. Using an approximate Bayesian computation approach, we reconstruct the demographic expansions associated with the segregation of primitive and fat-tailed phenotypes. These results together with archaeological evidence and historical data suggested the first expansion of early domestic hair sheep and the later expansion of fat-tailed sheep occurred ∼11,800-9,000 years BP and ∼5,300-1,700 years BP, respectively. These findings provide important insights into the history of migration and pastoralism of sheep across the Old World, which was associated with different breeding goals during the Neolithic agricultural revolution

Whole-Genome Resequencing of Worldwide Wild and Domestic Sheep Elucidates Genetic Diversity, Introgression, and Agronomically Important Loci

Domestic sheep and their wild relatives harbor substantial genetic variants that can form the backbone of molecular breeding, but their genome landscapes remain understudied. Here, we present a comprehensive genome resource for wild ovine species, landraces and improved breeds of domestic sheep, comprising high-coverage (∼16.10×) whole genomes of 810 samples from 7 wild species and 158 diverse domestic populations. We detected, in total, ∼121.2 million single nucleotide polymorphisms, ∼61 million of which are novel. Some display significant (P < 0.001) differences in frequency between wild and domestic species, or are private to continent-wide or individual sheep populations. Retained or introgressed wild gene variants in domestic populations have contributed to local adaptation, such as the variation in the HBB associated with plateau adaptation. We identified novel and previously reported targets of selection on morphological and agronomic traits such as stature, horn, tail configuration, and wool fineness. We explored the genetic basis of wool fineness and unveiled a novel mutation (chr25: T7,068,586C) in the 3'-UTR of IRF2BP2 as plausible causal variant for fleece fiber diameter. We reconstructed prehistorical migrations from the Near Eastern domestication center to South-and-Southeast Asia and found two main waves of migrations across the Eurasian Steppe and the Iranian Plateau in the Early and Late Bronze Ages. Our findings refine our understanding of genome variation as shaped by continental migrations, introgression, adaptation, and selection of sheep

Legacy of draught cattle breeds of South India: Insights into population structure, genetic admixture and maternal origin.

The present study is the first comprehensive report on diversity, population structure, genetic admixture and mitochondrial DNA variation in South Indian draught type zebu cattle. The diversity of South Indian cattle was moderately high. A significantly strong negative correlation coefficient of -0.674 (P6.25%) was observed in Punganur, Vechur, Umblachery and Pulikulam cattle breeds. Two major maternal haplogroups, I1 and I2, typical of zebu cattle were observed, with the former being predominant than the later. The pairwise differences among the I2 haplotypes of South Indian cattle were relatively higher than West Indian (Indus valley site) zebu cattle. The results indicated the need for additional sampling and comprehensive analysis of mtDNA control region variations to unravel the probable location of origin and domestication of I2 zebu lineage. The present study also revealed major concerns on South Indian zebu cattle (i) risk of endangerment due to small effective population size and high rate of inbreeding (ii) lack of sufficient purebred zebu bulls for breeding and (iii) increasing level of taurine admixture in zebu cattle. Availability of purebred semen for artificial insemination, incorporation of genomic/molecular information to identify purebred animals and increased awareness among farmers will help to maintain breed purity, conserve and improve these important draught cattle germplasms of South India

Allele count and Allele frequency data at 27 microsatellite marker loci in three breeds of Myanmar goats

The file consists of two sheets; First sheet contains allele count data at 27 microsatellite marker loci in three breeds of Myanmar goats, Jade Ni (JNI), Nyaung Oo (NYO) and Waithar Li (WTL). Second sheet contains allele frequency data at 27 microsatellite marker loci in three breeds of Myanmar goats, Jade Ni (JNI), Nyaung Oo (NYO) and Waithar Li (WTL)