Genome-wide association study reveals novel candidate genes for litter size in Markhoz goats

IntroductionThe Markhoz goat is the only breed that can produce high-quality fiber called mohair in Iran; however, the size of its population has faced a dramatic decline during the last decades, mainly due to the reluctance of farmers to rear Markhoz goats caused by a reduction in goat production income. Litter size at birth (LSB) and weaning (LSW) are two economically important reproductive traits for local goat breeders and have the potential of increasing the population growth rate. The present study was aimed to identify possible genomic regions that are associated with LSB and LSW in Markhoz goats using a genome-wide association study (GWAS). MethodsTo this end, 136 Markhoz goats with record(s) of kidding were selected for GWAS using the Illumina Caprine 50K bead chip. The individual breeding values (BV) of available LSB and LSW records estimated under an animal mixed model were used as the dependent variable in the GWAS, thereby incorporating repeated categorical variables of litter size. ResultsFour SNPs on chromosomes 2, 20 and 21 were identified to be significantly associated (FDR p < 0.05) with LSB after multiple testing correction under a Bayesian-information and Linkage-disequilibrium Iteratively Nested Keyway (BLINK) model. Least-square analysis was performed to investigate the effects of detected genotypes on LSB. Ultimately, the GWAS results introduced six candidate genes, including GABRA5, AKAP13, SV2B, PPP1R1C, SSFA2 and TRNAS-GCU in a 100 kb adjacent region of the identified SNPs. Previous studies proposed functional roles of GABRA5 and AKAP13 genes in reproductive processes; however, the role of other candidate genes in reproduction is not clear. ConclusionThese findings warrant further investigation for use in marker-assisted selection programs in Markhoz goats

In silico investigation of uncoupling protein function in avian genomes

INTRODUCTION: The uncoupling proteins (UCPs) are involved in lipid metabolism and belong to a family of mitochondrial anionic transporters. In poultry, only one UCP homologue has been identified and experimentally shown to be associated with growth, feed conversion ratio, and abdominal fat according to its predominant expression in bird muscles. In endotherm birds, cell metabolic efficiency can be tuned by the rate of mitochondrial coupling. Thus, avUCP may be a key contributor to controlling metabolic rate during particular environmental changes. METHODS: This study aimed to perform a set of in-silico investigations primarily focused on the structural, biological, and biomimetic functions of avUCP. Thereby, using in silico genome analyses among 8 avian species (chicken, turkey, swallow, manakin, sparrow, wagtail, pigeon, and mallard) and a series of bioinformatic approaches, we provide phylogenetic inference and comparative genomics of avUCPs and investigate whether sequence variation can alter coding sequence characteristics, the protein structure, and its biological features. Complementarily, a combination of literature mining and prediction approaches was also applied to predict the gene networks of avUCP to identify genes, pathways, and biological crosstalk associated with avUCP function. RESULTS: The results showed the evolutionary alteration of UCP proteins in different avian species. Uncoupling proteins in avian species are highly conserved trans membrane proteins as seen by sequence alignment, physio-chemical parameters, and predicted protein structures. Taken together, avUCP has the potential to be considered a functional marker for the identification of cell metabolic state, thermogenesis, and oxidative stress caused by cold, heat, fasting, transfer, and other chemical stimuli stresses in birds. It can also be deduced that avUCP, in migrant or domestic birds, may increase heat stress resistance by reducing fatty acid transport/b-oxidation and thermoregulation alongside antioxidant defense mechanisms. The predicted gene network for avUCP highlighted a cluster of 21 genes involved in response to stress and 28 genes related to lipid metabolism and the proton buffering system. Finally, among 11 enriched pathways, crosstalk of 5 signaling pathways including MAPK, adipocytokine, mTOR, insulin, ErbB, and GnRH was predicted, indicating a possible combination of positive or negative feedback among pathways to regulate avUCP functions. DISCUSSION: Genetic selection for fast-growing commercial poultry has unintentionally increased susceptibility to many kinds of oxidative stress, and so avUCP could be considered as a potential candidate gene for balancing energy expenditure and reactive oxygen species production, especially in breeding programs. In conclusion, avUCP can be introduced as a pleiotropic gene that requires the contribution of regulatory genes, hormones, pathways, and genetic crosstalk to allow its finely-tuned function

Constraint-Based, Score-Based and Hybrid Algorithms to Construct Bayesian Gene Networks in the Bovine Transcriptome

SIMPLE SUMMARY: In this study, we investigated and compared six different Bayesian network algorithms from three different categories to identify hub genes critical to gene expression networks activated in response to progesterone in the bovine uterus. We observed many common hub genes identified between constraint-based algorithms (CBAs) and hybrid algorithms (HAs), while it appeared that score-based algorithm (SBA) methods led to more accurate and relevant predictions of core genes. The results revealed that the identification of hub genes was affected by the type of network reconstruction and by the subsequently used topological parameters. Two identified genes known to have roles during pregnancy are ISG15 and DGAT2. The identified hub genes are associated with biological processes such as amino acid metabolism, hormonal signaling pathways and the immune system. Our analysis revealed a role for miRNAs in the regulation of this system. The biological and physiological roles (enzymatic and hormonal effects) of unannotated identified hub genes should be functionally validated by further studies. ABSTRACT: Bayesian gene networks are powerful for modelling causal relationships and incorporating prior knowledge for making inferences about relationships. We used three algorithms to construct Bayesian gene networks around genes expressed in the bovine uterus and compared the efficacies of the algorithms. Dataset GSE33030 from the Gene Expression Omnibus (GEO) repository was analyzed using different algorithms for hub gene expression due to the effect of progesterone on bovine endometrial tissue following conception. Six different algorithms (grow-shrink, max-min parent children, tabu search, hill-climbing, max-min hill-climbing and restricted maximum) were compared in three higher categories, including constraint-based, score-based and hybrid algorithms. Gene network parameters were estimated using the bnlearn bundle, which is a Bayesian network structure learning toolbox implemented in R. The results obtained indicated the tabu search algorithm identified the highest degree between genes (390), Markov blankets (25.64), neighborhood sizes (8.76) and branching factors (4.38). The results showed that the highest number of shared hub genes (e.g., proline dehydrogenase 1 (PRODH), Sam-pointed domain containing Ets transcription factor (SPDEF), monocyte-to-macrophage differentiation associated 2 (MMD2), semaphorin 3E (SEMA3E), solute carrier family 27 member 6 (SLC27A6) and actin gamma 2 (ACTG2)) was seen between the hybrid and the constraint-based algorithms, and these genes could be recommended as central to the GSE33030 data series. Functional annotation of the hub genes in uterine tissue during progesterone treatment in the pregnancy period showed that the predicted hub genes were involved in extracellular pathways, lipid and protein metabolism, protein structure and post-translational processes. The identified hub genes obtained by the score-based algorithms had a role in 2-arachidonoylglycerol and enzyme modulation. In conclusion, different algorithms and subsequent topological parameters were used to identify hub genes to better illuminate pathways acting in response to progesterone treatment in the bovine uterus, which should help with our understanding of gene regulatory networks in complex trait expression

Genetic parameters for daily milk somatic cell score and relationships with yield traits of primiparous Holstein cattle in Iran

Abstract Background Despite the importance of relationships between somatic cell score (SCS) and currently selected traits (milk, fat and protein yield) of Holstein cows, there was a lack of comprehensive literature for it in Iran. Therefore we tried to examine heritabilities and relationships between these traits using a fixed-regression animal model and Bayesian inference. The data set consisted of 1,078,966 test-day observations from 146,765 primiparous daughters of 1930 sires, with calvings from 2002 to 2013. Results Marginal posterior means of heritability estimates for SCS (0.03 ± 0.002) were distinctly lower than those for milk (0.204 ± 0.006), fat (0.096 ± 0.004) and protein (0.147 ± 0.005) yields. In the case of phenotypic correlations, the relationships between production and SCS were near zero at the beginning of lactation but become increasingly negative as days in milk increased. Although all environmental correlations between production and SCS were negative (−0.177 ± 0.007, −0.165 ± 0.008 and −0.152 ± 0.007 between SCS and milk, fat, and protein yield, respectively), slightly antagonistic genetic correlations were found; with posterior mean of relationships ranging from 0.01 ± 0.039 to 0.11 ± 0.036. This genetic opposition was distinctly higher for protein than for fat. Conclusion Although small, the positive genetic correlations suggest some genetic antagonism between desired increased milk production and reduced SCS (i.e., single-trait selection for increased milk production will also increase SCS)

Short communication: Estimation of genetic trends for body weight traits in Markhoz goat at different ages

The objective of the present study was to estimate genetic trends for body weight at different ages in Markhoz goat, including birth weight (BW, n = 4758), weaning weight (WW, n= 3685), 6-month weight (6MW, n = 3420), 9-month weight (9MW, n = 3032) and 12-month weight (12MW, n = 2697). Data and pedigree information were collected from 1992 until 2014 at the Breeding Center of Markhoz goat, Sanandaj, Iran. The GLM procedure of SAS was used for selecting the variables and identifying significant fixed effects in the equation of model. Various animal models were applied for genetic analysis and the best model was determined based on Akaike information criteria (AIC). Breeding values of animals were predicted using Wombat program. Genetic trends were obtained by regressing the average predicted breeding values on birth year for each trait. Based on the best model, direct estimated genetic trends were positive and significance for WW, 6MW, 9MW and 12 MW were 15.51, 26.28, 58.36 and 76.70 g/year, respectively (p<0.001). Maternal genetic trend for BW and WW were 0.61 and 5.47 g/year, respectively (p<0.01). The low and moderate generic trends obtained in the present study, indicated the possibility of growth traits improvements through genetic selection at all ages in Markhoz goat

Estimation of genetic trends for body weight traits in Markhoz goat at different ages

The objective of the present study was to estimate genetic trends for body weight at different ages in Markhoz goat, including birth weight (BW, n = 4758), weaning weight (WW, n= 3685), 6-month weight (6MW, n = 3420), 9-month weight (9MW, n = 3032) and 12-month weight (12MW, n = 2697). Data and pedigree information were collected from 1992 until 2014 at the Breeding Center of Markhoz goat, Sanandaj, Iran. The GLM procedure of SAS was used for selecting the variables and identifying significant fixed effects in the equation of model. Various animal models were applied for genetic analysis and the best model was determined based on Akaike information criteria (AIC). Breeding values of animals were predicted using Wombat program. Genetic trends were obtained by regressing the average predicted breeding values on birth year for each trait. Based on the best model, direct estimated genetic trends were positive and significance for WW, 6MW, 9MW and 12 MW were 15.51, 26.28, 58.36 and 76.70 g/year, respectively (p<0.001). Maternal genetic trend for BW and WW were 0.61 and 5.47 g/year, respectively (p<0.01). The low and moderate generic trends obtained in the present study, indicated the possibility of growth traits improvements through genetic selection at all ages in Markhoz goat

Estimation of Inbreeding Coefficient and Its Effects on Lamb Survival in Sheep

Introduction The mating of related individuals produces an inbred offspring and leads to an increased homozygosity in the progeny, genetic variance decrease within families and increase between families. The ration of homozygosity for individuals was calculated by inbreeding coefficient. Inbred individuals may carry two alleles at a locus that are replicated from one gene in the previous generations, called identical by descent. The inbreeding coefficient should be monitored in a breeding program, since it plays an important role at decreasing of homeostasis, performance, reproduction and viability. The trend of inbreeding is an indicator for determining of inbreeding level in the herd. Inbreeding affects both phenotypic means of traits and genetic variances within population, thus it is an important factor for delimitations of genetic progress in a population. Reports showed an inbreeding increase led to decrease of phenotypic value in some of the productive and reproductive traits. Materials and Methods In the current study, the pedigree data of 14030 and 6215 records of Baluchi and Iranblack lambs that collected from 1984 to 2011 at the Abbasabad Sheep Breeding Station in Mashhad, Iran, 3588 records of Makoei lambs that collected from 1994 to 2011 at the Makoei sheep breeding station and 6140, records of Zandi lambs that collected from 1991 to 2011 at the Khejir Sheep Breeding Station in Tehran, Iran were used to estimating the inbreeding coefficient and its effects on lamb survival in these breeds. Lamb survival trait was scored as 1 and 0 for lamb surviving and not surviving at weaning weight, respectively. Inbreeding coefficient was estimated by relationship matrix algorithm (A=TDT') methodology using the CFC software program. Effects of inbreeding coefficient on lamb survival were estimated by restricted maximum likelihood (REML) method under 12 different animal models using ASReml 3.0 computer programme. Coefficient of inbreeding for each lamb added to models as a covariate. The most appropriate model for this trait was determined by Akaike’s Information Criterion (AIC) test. Results and Discussion The number of survival records for Baluchi, Iranblack, Makoei and Zandi sheep breeds were 10793, 4826, 3588 and 6140, respectively. The inbred individuals were 17.63, 58.25, 4.88 and 36.32 per cent for Baluchi, Iranblack, Makoei and Zandi sheep, respectively, (2473, 3620, 175 and 2230 head respectively). The mean of inbreeding coefficient for whole and inbred populations for Baluchi lambs were 0.66 and 3.73 per cent, respectively, for Iranblack lambs were 4.59 and 7.90 per cent, respectively, for Makoei lambs were 0.25 and 4.86 per cent, respectively and for Zandi lambs were 1.22 and 3.61 per cent, respectively. Maximum of inbreeding coefficient for Baluchi, Iranblack, Makoei and Zandi lambs was 31.25, 34.70, 25.00 and 31.35 per cent, respectively. The mean of lamb survival in Whole and inbred population for Baluchi lambs were 89.11 and 88.30 per cent, respectively, for Iranblack lambs were 84.44 and 83.84 per cent, respectively, for Makoei lambs were 90.40 and 86.95 per cent, respectively and for Zandi lambs were 87.37 and 86.90 per cent, respectively. The average of inbreeding coefficient for 4 breeds was increased. The estimation of positive inbreeding coefficient trend for Baluchi, Iranblack, Makoei and Zandi were 0.035±0.012, 0.31±0.03, 0.010±0.012 and 0.020±0.012 per cent on each year, respectively. The most suitable model for survival in Baluchi, Iranblack, Makoei and Zandi breeds was 7, 12, 2 and 1, respectively. The regression coefficient of inbreeding on lamb survival were -0.26±0.11, -0.35±0.11, -0.25±1.83 and -0.04±0.20 per cent for Baluchi, Iranblack, Makoei and Zandi sheep, respectively. Conclusion The levels of inbreeding below 5% in whole population, or annual rates of inbreeding under 1% unlikely result in substantial reduction of performance and economic income in sheep production and serious genetic variation in the population. Inbreeding depression was observed for survival trait although the levels of inbreeding coefficient were acceptable in all of the breeds investigated in this study. Therefore, the general policy in the flocks should be continued to avoid mating between close relative parents and use of enough sires and dams selected per annum. Estimated inbreeding coefficients for Baluchi and Iranblack breeds showed high degree of close mating in these herd and due to the significant effect of inbreeding on survival, it is suggested that this breeding stations should use a breeding plan to avoid mating of close relative animals

Effects of Imported Semen Based on Different Selection Indices on Some Production and Reproduction Traits in Iranian Holstein Cattle

The aim of the present study was to evaluate the effects of imported semen of Holstein bulls from different countries on the economic traits of their daughters using the Lifetime Net Income (LNI) index in various climates of Iran. The data included the first lactation records of 274,057 Holstein cows collected during 1993 to 2017 by the Animal Breeding Center of Iran from 10 large dairy farms located in various provinces of Iran. The investigated traits included milk, fat and protein yields, calving age and calving interval. Breeding values of progenies were predicted by the Best Linear Unbiased Prediction (BLUP) method under the multi-trait animal model using DMU software. The genetic-economic merit of the progenies was estimated by the LNI index. There were significant differences between the estimated breeding values (EBVs) of sire groups (based on bull semen origin) for milk, fat and protein yields, calving age and calving interval in each climate (p &lt; 0.01). The obtained results showed that the highest least-square means of LNI index in semi-cold, moderate and warm climates belonged to the daughters of French sires; however, daughters of German sires were estimated to have the highest least-square means in the cold climate

Comparison of different selection methods for improving litter size in sheep using computer simulation

Aim of study: To assess selection methods via introgression to improve litter size in native and synthetic sheep breeds.Area of study: Sanandaj, Kurdistan, Iran.Material and methods: Selection approaches were performed using classical, genomic, gene-assisted classical (GasClassical) and gene-assisted genomic (GasGenomic) selection. Litter size trait with heritability of 0.1 including two chromosomes was simulated. On chromosome 1, a single QTL as the major gene was created to explain 40% of the total additive genetic variance. After simulation of a historical population, the animals from the last historical population were split into two populations. For the next 7 generations, animals were selected for favorable or unfavorable alleles to create distinct breeds of A or B, respectively. Then from the last generation, both males and females from breed B were selected to create a native population. On the other hand, males from breed A and females from breed B were mated to simulate a synthetic population. Finally, intra-population selections were carried out based on high breeding values during the last five generations.Main results: The genetic gain in the synthetic breed was higher than that of the native breed under all selection methods. The frequencies of favorable alleles after five generations in the classical, genomic, GasClassical and GasGenoimc selection approaches in the synthetic breed were 0.623, 0.730, 0.850 and 0.848, respectively.Research highlights: Combining gene-assisted selection with classical or genomic selection has the potential to improve genetic gain and increase the frequencies of favorable allele for litter size in sheep

Genetic diversity and signatures of selection in four indigenous horse breeds of Iran

Indigenous Iranian horse breeds were evolutionarily affected by natural and artificial selection in distinct phylogeographic clades, which shaped their genomes in several unique ways. The aims of this study were to evaluate the genetic diversity and genomewide selection signatures in four indigenous Iranian horse breeds. We evaluated 169 horses from Caspian (n = 21), Turkmen (n = 29), Kurdish (n = 67), and Persian Arabian (n = 52) populations, using genomewide genotyping data. The contemporary effective population sizes were 59, 98, 102, and 113 for Turkmen, Caspian, Persian Arabian, and Kurdish breeds, respectively. By analysis of the population genetic structure, we classified the north breeds (Caspian and Turkmen) and west/southwest breeds (Persian Arabian and Kurdish) into two phylogeographic clades reflecting their geographic origin. Using the de-correlated composite of multiple selection signal statistics based on pairwise comparisons, we detected a different number of significant SNPs under putative selection from 13 to 28 for the six pairwise comparisons (FDR < 0.05). The identified SNPs under putative selection coincided with genes previously associated with known QTLs for morphological, adaptation, and fitness traits. Our results showed HMGA2 and LLPH as strong candidate genes for height variation between Caspian horses with a small size and the other studied breeds with a medium size. Using the results of studies on human height retrieved from the GWAS catalog, we suggested 38 new putative candidate genes under selection. These results provide a genomewide map of selection signatures in the studied breeds, which represent valuable information for formulating genetic conservation and improved breeding strategies for the breeds