Siavash Salek Ardestani

Fixation index (F_st) statistics provide critical insights into evolutionary processes affecting the structure of genetic variation within and among populations. F_st statistics have been widely applied in population and evolutionary genetics to identify genomic regions targeted by selection pressures. The FSTest 1.3 software was developed to estimate four F_st statistics of Hudson, Weir and Cockerham, Nei, and Wright using high-throughput genotyping or sequencing data. Here, we introduced FSTest 1.3 and compared its performance with two widely used software VCFtools 0.1.16 and PLINK 2.0. Chromosome 1 of 1000 Genomes Phase III variant data belonging to South Asian (n = 211) and African (n = 274) populations were included as an example case in this study. Different F_st estimates were calculated for each single-nucleotide polymorphism (SNP) in a pairwise comparison of South Asian against African populations, and the results of FSTest 1.3 were confirmed by VCFtools 0.1.16 and PLINK 2.0. Two different sliding window approaches, one based on a fixed number of SNPs and another based on a fixed number of base pair (bp) were conducted using FSTest 1.3 and VCFtools 0.1.16. Our results showed that regions with low coverage genotypic data could lead to an overestimation of F_st in sliding window analysis using a fixed number of bp. FSTest 1.3 could mitigate this challenge by estimating the average of consecutive SNPs along the chromosome. FSTest 1.3 allows direct analysis of VCF files with a small amount of code and can calculate F_st estimates on a desktop computer for more than a million SNPs in a few minutes. FSTest 1.3 is freely available at https://github.com/similab/FSTest.

Following domestication, rice cultivars have been spread worldwide to different climates and have experienced selection pressures to improve desirable traits. This has resulted in diverse cultivars that display variations in phenotypic traits, such as stress tolerance, grain size, and yield. To better understand the genomic composition arising from cultivar’s development and local adaptation, high-density genotypes (containing 286,183 single-nucleotide polymorphisms after the quality control) of 1284 rice cultivars of aus, indica, and temperate and tropical japonica were scanned for diversifying signatures by applying a pairwise comparison of fixation index (F_st) test. Each cultivar’s population was investigated for contemporary selection using the integrated haplotype score test. Signatures of diversifying selection among the pairwise comparisons were found in genomic regions mainly involved in response to stress (pathogens, drought, heat, cold) and development and morphology of various structures, such as root, pollen, spikelet, and grain. The most significant diversification signal between indica and japonica cultivars was detected at the location of ROX2 gene. Aus with indica comparison detected the most divergent signal at important candidate genes of OsEXPA8 and OsEXPA9, whereas temperate with tropical japonica comparison resulted in two well-known candidate genes OsHCT4 and OsGpx4. Recent selection analysis detected different patterns of contemporary selection in genomic regions related to rice breeding standard criteria such as stress tolerance, seed germination, starch content, and flowering time. Our findings highlight the underlying molecular basis of adaptive divergence and propose that modern rice breeding may provide additional diversification among rice cultivars.

Fixation index (Fst) statistics provide critical insights into the evolutionary processes affecting the structure of genetic variation within and among populations. The Fst statistics have been widely applied in population and evolutionary genetics to identify genomic regions targeted by selection pressures. The FSTest 1.3 software was developed to estimate four Fst statistics of Hudson, Weir and Cockerham, Nei, and Wright using high-throughput genotyping or sequencing data. Here, we introduced FSTest 1.3 and compared its performance with two widely used software of VCFtools 0.1.16 and PLINK 2.0. Chromosome 1 of 1000 Genomes Phase III variant data belonging to South Asian (N = 211) and African (N = 274) populations were included as an example case in this study. Different Fst estimates were calculated for each single nucleotide polymorphism (SNP) in a pairwise comparison of South Asian against African populations, and the results of FSTest 1.3 were confirmed by VCFtools 0.1.16 and PLINK 2.0. Two different sliding window approaches, one based on a fixed number of SNPs and another based on a fixed number of base pair (bp) were conducted using FSTest 1.3 and VCFtools 0.1.16. Our results showed that regions with low coverage genotypic data could lead to an overestimation of Fst in sliding window analysis using a fixed number of bp. FSTest 1.3 could mitigate this challenge by estimating the average of consecutive SNPs along the chromosome. FSTest 1.3 allows direct analysis of VCF files with a small amount of code and can calculate Fst estimates on a desktop computer for more than a million SNPs in a few minutes. FSTest 1.3 is freely available at https://github.com/similab/FSTest .

The genetic structure and characteristics of Iranian native breeds are yet to be comprehensibly investigated and studied. Therefore, we employed genomic information of 364 Iranian native horses representing the Asil (n = 109), Caspian (n = 40), Dareshuri (n = 44), Kurdish (n = 95), and Turkoman (n = 76) breeds to reveal the genetic structure and characteristics. For these and 19 other horse breeds, principal component analysis, Bayesian model-based, Neighbor-Net, and bootstrap-based TreeMix approaches were applied to investigate and compare their genetic structure. Additionally, three haplotype-based methods including haplotype homozygosity pooled, integrated haplotype score, and number of segregating sites by length were applied to trace genomic footprints of selection of Asil, Caspian, Dareshuri, Kurdish, and Turkoman groups. Then, the Mahalanobis distance based on the negative-log₁₀ rank-based P-values was estimated based on the haplotype homozygosity pooled, integrated haplotype score, and number of segregating sites by length values. Asil, Caspian, Dareshuri, Kurdish, and Turkoman can be categorized into five different genetic clusters. Based on the top 1% of Mahalanobis distance based on the negative-log₁₀ rank-based P-values of SNPs, we identified 24 SNPs formerly reported to be associated with different traits and >100 genes undergoing selection pressures in Asil, Caspian, Dareshuri, Kurdish, and Turkoman. The detected QTL undergoing selection pressures were associated with withers height, equine metabolic syndrome, overall body size, insect bite hypersensitivity, guttural pouch tympany, white markings, Rhodococcus equi infection, jumping test score, alternate gaits, and body weight traits. Our findings will aid to have a better perspective of the genetic characteristics and population structure of Asil, Caspian, Dareshuri, Kurdish, and Turkoman horses as Iranian native horse breeds.

Genetic introgression from interbreeding hybridization of European Bos taurus taurus (EBT) and Indian Bos taurus indicus (IBI) cattle breeds have been widely used to combine the climatic resilience of the IBI cattle and the higher productivity of EBT when forming new composite beef cattle (CB) populations. The subsequent breeding strategies have shifted their initial genomic compositions. To uncover population structure, signatures of selection, and potential introgression events in CB populations, high-density genotypes [containing 492,954 single nucleotide polymorphisms (SNPs) after the quality control] of 486 individuals from 15 cattle breeds, including EBT, IBI, and CB populations, along with two Bos grunniens genotypes as outgroup were used in this study. Then, in-depth population genetics analyses were performed for three CB breeds of Beefmaster, Brangus, and Santa Gertrudis. Neighbor-joining, principal components, and admixture analyses confirmed the historical introgression of EBT and IBI haplotypes into CB breeds. The f_dM statistics revealed that only 12.9% of CB populations’ genetic components are of IBI origin. The results of signatures of selection analysis indicated different patterns of selection signals in the three CB breeds with primary pressure on pathways involved in protein processing and stress response in Beefmaster, cell proliferation regulation and immune response in Brangus, and amino acids and glucose metabolisms in Santa Gertrudis. An average of >90% of genomic regions underlying selection signatures were of EBT origin in the studied CB populations. Investigating the CB breeds’ genome allows the estimation of EBT and IBI ancestral proportions and the locations within the genome where either taurine or indicine origin alleles are under selective pressure. Such findings highlight various opportunities to control the selection process more efficiently and explore complementarity at the genomic level in CB populations.

Dareshouri, Arabian, and Akhal-Teke are three Middle Eastern horse breeds that have been selected for endurance and adaptation to harsh climates. Deciphering the genetic characteristics of these horses by tracing selection footprints and copy number of variations will be helpful in improving our understanding of equine breeds' development and adaptation. For this purpose, we sequenced the whole-genome of four Dareshouri horses using Illumina Hiseq panels and compared them with publicly available whole-genome sequences of Arabian (n=3) and Akhal-Teke (n=3) horses . Three tests of FLK, hapFLK, and pooled heterozygosity were applied using a sliding window (window size=100kb, step size=50kb) approach to detect putative selection signals. Copy number variation analysis was applied to investigate copy number of variants (CNVs), and the results were used to suggest selection signatures involving CNVs. Whole-genome sequencing demonstrated 8,837,950 single nucleotide polymorphisms (SNPs) in autosomal chromosomes. We suggested 58 genes and three quantitative trait loci (QTLs), including some related to horse gait, insect bite hypersensitivity, and withers height, based on selective signals detected by adjusted p-value of Mahalanobis distance based on the rank-based P-values (Md-rank-P) method. We proposed 12 genomic regions under selection pressure involving CNVs which were previously reported to be associated with metabolism energy (SLC5A8), champagne dilution in horses (SLC36A1), and synthesis of polyunsaturated fatty acids (FAT2). Only 10 Middle Eastern horses were tested in this study; therefore, the conclusions are speculative. Our findings are useful to better understanding the evolution and adaptation of Middle Eastern horse breeds.

Controlling extra fat deposition is economically favorable in modern swine industry. Understanding the genetic architecture of fat deposition traits such as body mass index (BMI) can help in improving genomic selection for such traits. We utilized a weighted single-step genome-wide association study (WssGWAS) to detect genetic regions and candidate genes associated with BMI in a Yorkshire pig population. Three extended haplotype homozygosity (EHH)-related statistics were also incorporated within a de-correlated composite of multiple signals (DCMS) framework to detect recent selection signatures signals. Overall, the full pedigree consisted of 7,016 pigs, of which 5,561 had BMI records and 598 pigs were genotyped with an 80 K single nucleotide polymorphism (SNP) array. Results showed that the most significant windows (top 15) explained 9.35% of BMI genetic variance. Several genes were detected in regions previously associated with pig fat deposition traits and treated as potential candidate genes for BMI in Yorkshire pigs: FTMT, SRFBP1, KHDRBS3, FOXG1, SOD3, LRRC32, TSKU, ACER3, B3GNT6, CCDC201, ADCY1, RAMP3, TBRG4, CCM2. Signature of selection analysis revealed multiple candidate genes previously associated with various economic traits. However, BMI genetic variance explained by regions under selection pressure was minimal (1.31%). In conclusion, candidate genes associated with Yorkshire pigs’ BMI trait were identified using WssGWAS. Gene enrichment analysis indicated that the identified candidate genes were enriched in the insulin secretion pathway. We anticipate that these results further advance our understanding of the genetic architecture of BMI in Yorkshire pigs and provide information for genomic selection for fat deposition in this breed.

Feed costs are the largest expense in mink production systems. Therefore, improvement of feed efficiency (FE) is the best way to use limited resources efficiently and increase the mink industry’s sustainability. The objectives of this project are to 1) identify the genetic relationships among different FE measures and their component traits, and 2) discover the genetic architecture of FE and implement genomic selection for FE traits to increase the genetic gain in American mink. Final body weight (FBW), final body length (FBL), daily feed intake (DFI), average daily gain (ADG), feed conversion ratio (FCR), residual feed intake (RFI), residual gain (RG), residual intake and gain (RIG) and Kleiber ratio (KR) traits were measured based on the phenotypic records on 1,088 American mink from the Canadian Center for Fur Animal Research (Nova Scotia, Canada). Univariate models were applied to test the significance of sex, color type, age, and nested Row(Year) as fixed effects and random maternal effect. Genetic parameters were estimated via bivariate models using ASReml-R 4. Estimated heritabilities (±SE) were 0.38±0.10, 0.36±0.10, 0.25±0.10, 0.34±0.09, 0.38±0.08, 0.37±0.07, 0.29±0.10, 0.32±0.10 and 0.34±0.10 for FBW, FBL, DFI, ADG, FCR, RFI, RG, RIG and KR, respectively. RFI showed non-significant (P >0.05) genetic correlations with component traits such as FBW (0.00±0.17) and FBL (0.30±0.16) but significant (P < 0.05) high genetic correlation with DFI (0.74±0.09), indicating that selection based on RFI will reduce the feed intake without any negative effects on the size and growth. The estimated genetic parameters for FE traits suggested the possibility to implement genetic/genomic selection to improve the FE in American mink. Consequently, the ongoing project on genetic mapping and genomic selection will enhance the knowledge of FE and improve the efficacy of selection for more feed-efficient mink.

Improvement of prediction accuracy of estimated breeding values (EBVs) can lead to increased profitability for swine breeding companies. This study was performed to compare the accuracy of different popular genomic prediction methods and traditional best linear unbiased prediction (BLUP) for future performance of back-fat thickness (BFT), average daily gain (ADG), and loin muscle depth (LMD) in Canadian Duroc, Landrace, and Yorkshire swine breeds. In this study, 17,019 pigs were genotyped using Illumina 60K and Affymetrix 50K panels. After quality control and imputation steps, a total of 41,304, 48,580, and 49,102 single-nucleotide polymorphisms remained for Duroc (n = 6,649), Landrace (n = 5,362), and Yorkshire (n = 5,008) breeds, respectively. The breeding values of animals in the validation groups (n = 392–774) were predicted before performance test using BLUP, BayesC, BayesCπ, genomic BLUP (GBLUP), and single-step GBLUP (ssGBLUP) methods. The prediction accuracies were obtained using the correlation between the predicted breeding values and their deregressed EBVs (dEBVs) after performance test. The genomic prediction methods showed higher prediction accuracies than traditional BLUP for all scenarios. Although the accuracies of genomic prediction methods were not significantly (P > 0.05) different, ssGBLUP was the most accurate method for Duroc-ADG, Duroc-LMD, Landrace-BFT, Landrace-ADG, and Yorkshire-BFT scenarios, and BayesCπ was the most accurate method for Duroc-BFT, Landrace-LMD, and Yorkshire-ADG scenarios. Furthermore, BayesCπ method was the least biased method for Duroc-LMD, Landrace-BFT, Landrace-ADG, Yorkshire-BFT, and Yorkshire-ADG scenarios. Our findings can be beneficial for accelerating the genetic progress of BFT, ADG, and LMD in Canadian swine populations by selecting more accurate and unbiased genomic prediction methods.

The use of DNA methylation signatures to predict chronological age and aging rate is of interest in many fields, including disease prevention and treatment, forensics, and anti-aging medicine. Although a large number of methylation markers are significantly associated with age, most age-prediction methods use a few markers selected based on either previously published studies or datasets containing methylation information. Here, we implemented reproducing kernel Hilbert spaces (RKHS) regression and a ridge regression model in a Bayesian framework that utilized phenotypic and methylation profiles simultaneously to predict chronological age. We used over 450,000 CpG sites from the whole blood of a large cohort of 4409 human individuals with a range of 10–101 years of age. Models were fitted using adjusted and un-adjusted methylation measurements for cell heterogeneity. Un-adjusted methylation scores delivered a significantly higher prediction accuracy than adjusted methylation data, with a correlation between age and predicted age of 0.98 and a root mean square error (RMSE) of 3.54 years in un-adjusted data, and 0.90 (correlation) and 7.16 (RMSE) years in adjusted data. Reducing the number of predictors (CpG sites) through subset selection improved predictive power with a correlation of 0.98 and an RMSE of 2.98 years in the RKHS model. We found distinct global methylation patterns, with a significant increase in the proportion of methylated cytosines in CpG islands and a decreased proportion in other CpG types, including CpG shore, shelf, and open sea (P < 5e-06). Epigenetic drift seemed to be a widespread phenomenon as more than 97% of the age-associated methylation sites had heteroscedasticity. Apparent methylomic aging rate (AMAR) had a sex-specific pattern, with an increase in AMAR in females with age related to males.