Animal & Avian Sciences Research Works
Permanent URI for this collectionhttp://hdl.handle.net/1903/1600
Browse
18 results
Search Results
Item Characterization of Copy Number Variation’s Potential Role in Marek’s Disease(MDPI, 2017-05-09) Xu, Lingyang; He, Yanghua; Ding, Yi; Sun, Guirong; Carrillo, Jose Adrian; Li, Yaokun; Ghaly, Mona M.; Ma, Li; Zhang, Huanmin; Liu, George E.; Song, JiuzhouMarek’s Disease (MD) is a highly contagious pathogenic and oncogenic disease primarily affecting chickens. Chicken Lines 63 and 72, as well as their recombinant congenic strains (RCS) with varied susceptibility to MD, are ideal models to study the complex mechanisms of genetic resistance to MD. In this study, we investigated copy number variation (CNV) in these inbred chicken lines using the Affymetrix Axiom HD 600 K SNP genotyping array. We detected 393 CNV segments across all ten chicken lines, of which 12 CNVs were specifically identified in Line 72. We then assessed genetic structure based on CNV and observed markedly different patterns. Finally, we validated two deletion events in Line 72 and correlated them with genes expression using qPCR and RNA-seq, respectively. Our combined results indicated that these two CNV deletions were likely to contribute to MD susceptibility.Item Insights from Initial Variant Detection by Sequencing Single Sperm in Cattle(MDPI, 2021-11-15) Yang, Liu; Gao, Yahui; Boschiero, Clarissa; Li, Li; Zhang, Hongping; Ma, Li; Liu, George E.Meiotic de novo mutation (DNM) is one of the important phenomena contributing to gamete genome diversity. However, except for humans and a few model organisms, they are not well studied in livestock, including cattle. Moreover, bulk sperm samples have been routinely utilized in experiments, which include millions of single sperm cells and only report high-frequency variants. In this study, we isolated and sequenced 143 single sperms from two Holstein bulls and identified hundreds of candidate DNM events in ten sperms with deep sequencing coverage. We estimated DNM rates ranging from 1.08 × 10−8 to 3.78 × 10−8 per nucleotide per generation. We further validated 12 out of 14 selected DNM events using Sanger sequencing. To our knowledge, this is the first single sperm whole-genome sequencing effort in livestock, which provided useful information for future studies of point mutations and male fertility. Our preliminary results pointed out future research directions and highlighted the importance of uniform whole genome amplification, deep sequence coverage, and dedicated software pipelines for genetic variant detection using single-cell sequencing data.Item Comparative transcriptome in large-scale human and cattle populations(Springer Nature, 2022-08-22) Yao, Yuelin; Liu, Shuli; Xia, Charley; Gao, Yahui; Pan, Zhangyuan; Canela-Xandri, Oriol; Khamseh, Ava; Rawlik, Konrad; Wang, Sheng; Li, Bingjie; Zhang, Yi; Pairo-Castineira, Erola; D’Mellow, Kenton; Li, Xiujin; Yan, Ze; Li, Cong-jun; Yu, Ying; Zhang, Shengli; Ma, Li; Cole, John B.; Ross, Pablo J.; Zhou, Huaijun; Haley, Chris; Liu, George E.; Fang, Lingzhao; Tenesa, AlbertCross-species comparison of transcriptomes is important for elucidating evolutionary molecular mechanisms underpinning phenotypic variation between and within species, yet to date it has been essentially limited to model organisms with relatively small sample sizes. Here, we systematically analyze and compare 10,830 and 4866 publicly available RNA-seq samples in humans and cattle, respectively, representing 20 common tissues. Focusing on 17,315 orthologous genes, we demonstrate that mean/median gene expression, inter-individual variation of expression, expression quantitative trait loci, and gene co-expression networks are generally conserved between humans and cattle. By examining large-scale genome-wide association studies for 46 human traits (average n = 327,973) and 45 cattle traits (average n = 24,635), we reveal that the heritability of complex traits in both species is significantly more enriched in transcriptionally conserved than diverged genes across tissues. In summary, our study provides a comprehensive comparison of transcriptomes between humans and cattle, which might help decipher the genetic and evolutionary basis of complex traits in both species.Item Investigation of rumen long noncoding RNA before and after weaning in cattle(Springer Nature, 2022-07-20) Marceau, Alexis; Gao, Yahui; Baldwin VI, Ransom L.; Li, Cong-jun; Jiang, Jicai; Liu, George E.; Ma, LiThis study aimed to identify long non-coding RNA (lncRNA) from the rumen tissue in dairy cattle, explore their features including expression and conservation levels, and reveal potential links between lncRNA and complex traits that may indicate important functional impacts of rumen lncRNA during the transition to the weaning period. A total of six cattle rumen samples were taken with three replicates from before and after weaning periods, respectively. Total RNAs were extracted and sequenced with lncRNA discovered based on size, coding potential, sequence homology, and known protein domains. As a result, 404 and 234 rumen lncRNAs were identified before and after weaning, respectively. However, only nine of them were shared under two conditions, with 395 lncRNAs found only in pre-weaning tissues and 225 only in post-weaning samples. Interestingly, none of the nine common lncRNAs were differentially expressed between the two weaning conditions. LncRNA averaged shorter length, lower expression, and lower conservation scores than the genome overall, which is consistent with general lncRNA characteristics. By integrating rumen lncRNA before and after weaning with large-scale GWAS results in cattle, we reported significant enrichment of both pre- and after-weaning lncRNA with traits of economic importance including production, reproduction, health, and body conformation phenotypes. The majority of rumen lncRNAs are uniquely expressed in one of the two weaning conditions, indicating a functional role of lncRNA in rumen development and transition of weaning. Notably, both pre- and post-weaning lncRNA showed significant enrichment with a variety of complex traits in dairy cattle, suggesting the importance of rumen lncRNA for cattle performance in the adult stage. These relationships should be further investigated to better understand the specific roles lncRNAs are playing in rumen development and cow performance.Item Genome-wide recombination map construction from single sperm sequencing in cattle(Springer Nature, 2022-03-05) Yang, Liu; Gao, Yahui; Li, Mingxun; Park, Ki-Eun; Liu, Shuli; Kang, Xiaolong; Liu, Mei; Oswalt, Adam; Fang, Lingzhao; Telugu, Bhanu P.; Sattler, Charles G.; Li, Cong-jun; Cole, John B.; Seroussi, Eyal; Xu, Lingyang; Yang, Lv; Zhou, Yang; Li, Li; Zhang, Hongping; Rosen, Benjamin D.; Van Tassell, Curtis P.; Ma, Li; Liu, George E.Meiotic recombination is one of the important phenomena contributing to gamete genome diversity. However, except for human and a few model organisms, it is not well studied in livestock, including cattle. To investigate their distributions in the cattle sperm genome, we sequenced 143 single sperms from two Holstein bulls. We mapped meiotic recombination events at high resolution based on phased heterozygous single nucleotide polymorphism (SNP). In the absence of evolutionary selection pressure in fertilization and survival, recombination events in sperm are enriched near distal chromosomal ends, revealing that such a pattern is intrinsic to the molecular mechanism of meiosis. Furthermore, we further validated these findings in single sperms with results derived from sequencing its family trio of diploid genomes and our previous studies of recombination in cattle. To our knowledge, this is the first large-scale single sperm whole-genome sequencing effort in livestock, which provided useful information for future studies of recombination, genome instability, and male infertility.Item Towards the detection of copy number variation from single sperm sequencing in cattle(Springer Nature, 2022-03-17) Yang, Liu; Gao, Yahui; Oswalt, Adam; Fang, Lingzhao; Boschiero, Clarissa; Neupane, Mahesh; Sattler, Charles G.; Li, Cong-jun; Seroussi, Eyal; Xu, Lingyang; Yang, Lv; Li, Li; Zhang, Hongping; Rosen, Benjamin D.; Van Tassell, Curtis P.; Zhou, Yang; Ma, Li; Liu, George E.Copy number variation (CNV) has been routinely studied using bulk-cell sequencing. However, CNV is not well studied on the single-cell level except for humans and a few model organisms. We sequenced 143 single sperms of two Holstein bulls, from which we predicted CNV events using 14 single sperms with deep sequencing. We then compared the CNV results derived from single sperms with the bulk-cell sequencing of one bull’s family trio of diploid genomes. As a known CNV hotspot, segmental duplications were also predicted using the bovine ARS-UCD1.2 genome. Although the trio CNVs validated only some single sperm CNVs, they still showed a distal chromosomal distribution pattern and significant associations with segmental duplications and satellite repeats. Our preliminary results pointed out future research directions and highlighted the importance of uniform whole genome amplification, deep sequence coverage, and dedicated software pipelines for CNV detection using single cell sequencing data.Item Ruminant-specific multiple duplication events of PRDM9 before speciation(Springer Nature, 2017-03-14) Padhi, Abinash; Shen, Botong; Jiang, Jicai; Zhou, Yang; Liu, George E.; Ma, LiUnderstanding the genetic and evolutionary mechanisms of speciation genes in sexually reproducing organisms would provide important insights into mammalian reproduction and fitness. PRDM9, a widely known speciation gene, has recently gained attention for its important role in meiotic recombination and hybrid incompatibility. Despite the fact that PRDM9 is a key regulator of recombination and plays a dominant role in hybrid incompatibility, little is known about the underlying genetic and evolutionary mechanisms that generated multiple copies of PRDM9 in many metazoan lineages. The present study reports (1) evidence of ruminant-specific multiple gene duplication events, which likely have had occurred after the ancestral ruminant population diverged from its most recent common ancestor and before the ruminant speciation events, (2) presence of three copies of PRDM9, one copy (lineages I) in chromosome 1 (chr1) and two copies (lineages II & III) in chromosome X (chrX), thus indicating the possibility of ancient inter- and intra-chromosomal unequal crossing over and gene conversion events, (3) while lineages I and II are characterized by the presence of variable tandemly repeated C2H2 zinc finger (ZF) arrays, lineage III lost these arrays, and (4) C2H2 ZFs of lineages I and II, particularly the amino acid residues located at positions −1, 3, and 6 have evolved under strong positive selection. Our results demonstrated two gene duplication events of PRDM9 in ruminants: an inter-chromosomal duplication that occurred between chr1 and chrX, and an intra-chromosomal X-linked duplication, which resulted in two additional copies of PRDM9 in ruminants. The observation of such duplication between chrX and chr1 is rare and may possibly have happened due to unequal crossing-over millions of years ago when sex chromosomes were independently derived from a pair of ancestral autosomes. Two copies (lineages I & II) are characterized by the presence of variable sized tandem-repeated C2H2 ZFs and evolved under strong positive selection and concerted evolution, supporting the notion of well-established Red Queen hypothesis. Collectively, gene duplication, concerted evolution, and positive selection are the likely driving forces for the expansion of ruminant PRDM9 sub-family.Item Characterization of recombination features and the genetic basis in multiple cattle breeds(Springer Nature, 2018-04-27) Shen, Botong; Jiang, Jicai; Seroussi, Eyal; Liu, George E.; Ma, LiCrossover generated by meiotic recombination is a fundamental event that facilitates meiosis and sexual reproduction. Comparative studies have shown wide variation in recombination rate among species, but the characterization of recombination features between cattle breeds has not yet been performed. Cattle populations in North America count millions, and the dairy industry has genotyped millions of individuals with pedigree information that provide a unique opportunity to study breed-level variations in recombination. Based on large pedigrees of Jersey, Ayrshire and Brown Swiss cattle with genotype data, we identified over 3.4 million maternal and paternal crossover events from 161,309 three-generation families. We constructed six breed- and sex-specific genome-wide recombination maps using 58,982 autosomal SNPs for two sexes in the three dairy cattle breeds. A comparative analysis of the six recombination maps revealed similar global recombination patterns between cattle breeds but with significant differences between sexes. We confirmed that male recombination map is 10% longer than the female map in all three cattle breeds, consistent with previously reported results in Holstein cattle. When comparing recombination hotspot regions between cattle breeds, we found that 30% and 10% of the hotspots were shared between breeds in males and females, respectively, with each breed exhibiting some breed-specific hotspots. Finally, our multiple-breed GWAS found that SNPs in eight loci affected recombination rate and that the PRDM9 gene associated with hotspot usage in multiple cattle breeds, indicating a shared genetic basis for recombination across dairy cattle breeds. Collectively, our results generated breed- and sex-specific recombination maps for multiple cattle breeds, provided a comprehensive characterization and comparison of recombination patterns between breeds, and expanded our understanding of the breed-level variations in recombination features within an important livestock species.Item Genomic predictions combining SNP markers and copy number variations in Nellore cattle(Springer Nature, 2018-06-05) Hay, El Hamidi A.; Utsunomiya, Yuri T.; Xu, Lingyang; Zhou, Yang; Neves, Haroldo H. R.; Carvalheiro, Roberto; Bickhart, Derek M.; Ma, Li; Garcia, Jose Fernando; Liu, George E.Due to the advancement in high throughput technology, single nucleotide polymorphism (SNP) is routinely being incorporated along with phenotypic information into genetic evaluation. However, this approach often cannot achieve high accuracy for some complex traits. It is possible that SNP markers are not sufficient to predict these traits due to the missing heritability caused by other genetic variations such as microsatellite and copy number variation (CNV), which have been shown to affect disease and complex traits in humans and other species. In this study, CNVs were included in a SNP based genomic selection framework. A Nellore cattle dataset consisting of 2230 animals genotyped on BovineHD SNP array was used, and 9 weight and carcass traits were analyzed. A total of six models were implemented and compared based on their prediction accuracy. For comparison, three models including only SNPs were implemented: 1) BayesA model, 2) Bayesian mixture model (BayesB), and 3) a GBLUP model without polygenic effects. The other three models incorporating both SNP and CNV included 4) a Bayesian model similar to BayesA (BayesA+CNV), 5) a Bayesian mixture model (BayesB+CNV), and 6) GBLUP with CNVs modeled as a covariable (GBLUP+CNV). Prediction accuracies were assessed based on Pearson’s correlation between de-regressed EBVs (dEBVs) and direct genomic values (DGVs) in the validation dataset. For BayesA, BayesB and GBLUP, accuracy ranged from 0.12 to 0.62 across the nine traits. A minimal increase in prediction accuracy for some traits was noticed when including CNVs in the model (BayesA+CNV, BayesB+CNV, GBLUP+CNV). This study presents the first genomic prediction study integrating CNVs and SNPs in livestock. Combining CNV and SNP marker information proved to be beneficial for genomic prediction of some traits in Nellore cattle.Item Genetic assessment of inbred chicken lines indicates genomic signatures of resistance to Marek’s disease(Springer Nature, 2018-09-13) Xu, Lingyang; He, Yanghua; Ding, Yi; Liu, George E.; Zhang, Huanmin; Cheng, Hans H.; Taylor, Robert L. Jr.; Song, JiuzhouMarek’s disease (MD) is a highly contagious pathogenic and oncogenic disease primarily affecting chickens. However, the mechanisms of genetic resistance for MD are complex and not fully understood. MD-resistant line 63 and MD-susceptible line 72 are two highly inbred progenitor lines of White Leghorn. Recombinant Congenic Strains (RCS) were developed from these two lines, which show varied susceptibility to MD. We investigated genetic structure and genomic signatures across the genome, including the line 63 and line 72, six RCSs, and two reciprocally crossed flocks between the lines 63 and 72 (F1 63 × 72 and F1 72 × 63) using Affymetrix® Axiom® HD 600 K genotyping array. We observed 18 chickens from RCS lines were specifically clustered into resistance sub-groups distributed around line 63. Additionally, homozygosity analysis was employed to explore potential genetic components related to MD resistance, while runs of homozygosity (ROH) are regions of the genome where the identical haplotypes are inherited from each parent. We found several genes including SIK, SOX1, LIG4, SIK1 and TNFSF13B were contained in ROH region identified in resistant group (line 63 and RCS), and these genes have been reported that are contribute to immunology and survival. Based on FST based population differential analysis, we also identified important genes related to cell death and anti-apoptosis, including AKT1, API5, CDH13, CFDP and USP15, which could be involved in divergent selection during inbreeding process. Our findings offer valuable insights for understanding the genetic mechanism of resistance to MD and the identified genes could be considered as candidate biomarkers in further evaluation.