Zhi-Qiang Du

Iowa State University, Ames, Iowa, United States

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Publications (14)30.25 Total impact

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    ABSTRACT: BACKGROUND: Most studies on the origin and evolution of microRNA in the human genome have been focused on its relationship with repetitive elements and segmental duplications. However, duplication events at a smaller scale (<1 kb) could also contribute to microRNA expansion, as demonstrated in this study. RESULTS: Using comparative genome analysis and bioinformatics methods, we found nine novel expanded microRNA families enriched in short duplicated sequences in the human genome. Furthermore, novel genomic regions were found to contain microRNA paralogs for microRNA families previously analyzed to be related to segmental duplications. We found that for microRNA families expanded in the human genome, 14 families are specific to the primate lineage, and nine are non-specific, respectively. Two microRNA families (hsa-mir-1233 and hsa-mir-622) appear to be further expanded in the human genome, and were confirmed by fluorescence in situ hybridization. These novel microRNA families expanded in the human genome were mostly embedded in or close to proteins with conserved functions. Furthermore, besides the Alu element, L1 elements could also contribute to the origination of microRNA paralog families. CONCLUSIONS: Together, we found that small duplication events could also contribute to microRNA expansion, which could provide us novel insights on the evolution of human genome structure and function.
    BMC Genomics 02/2013; 14(1):98. · 4.40 Impact Factor
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    ABSTRACT: Small RNA represent several unique non-coding RNA classes that have important function in the development of germ cells and early embryonic development. Deep sequencing was performed on small RNA from cumulus cells, oocytes at GV and MII stages, as well as in vitro fertilized derived embryos at 60 h post fertilization (4- to 8-cell) and on Day 6 blastocysts. Additionally, a heterologous miRNA microarray method was also used to identify miRNA expressed in the oocyte during in vitro maturation. Similar to the expression analysis of other species, these data demonstrate dynamic expression regulation of multiple classes of non-coding RNA during oocyte maturation and development to the blastocyst stage. Mapping small RNA to the pig genome indicates dynamic distribution of small RNA organization across the genome. Additionally, a cluster of miRNA and piRNA was discovered on chromosome 6. Many of the small RNA mapped to annotated repetitive elements in the pig genome, of which the SINE/tRNA-Glu and LINE/L1 elements represented a large proportion. Two piRNA (piR84651 and piR16993) and 7 miRNA (MIR574, MIR24, LET7E, MIR23B, MIR30D, MIR320, and MIR30C) were further characterized using quantitative RT-PCR. Secretory carrier membrane protein 4 (SCAMP4) was predicted to be subject to posttranscriptional gene regulation mediated by small RNA, by annotating small RNA reads mapped to exonic regions in the pig genome. Consistent with the prediction results, SCAMP4 was further confirmed to be differentially expressed at both transcriptional and translational levels. These data establish a small RNA expression profile of the pig cumulus-oocyte complex and early embryos, and demonstrate their potential capacity to be utilized to make predictions of functional posttranscriptional regulatory events.
    Biology of Reproduction 08/2012; · 4.03 Impact Factor
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    ABSTRACT: The recent completion of the swine genome sequencing project and development of a high density porcine SNP array has made genome-wide association (GWA) studies feasible in pigs. Using Illumina's PorcineSNP60 BeadChip, we performed a pilot GWA study in 820 commercial female pigs phenotyped for backfat, loin muscle area, body conformation in addition to feet and leg (FL) structural soundness traits. A total of 51,385 SNPs were jointly fitted using Bayesian techniques as random effects in a mixture model that assumed a known large proportion (99.5%) of SNPs had zero effect. SNP annotations were implemented through the Sus scrofa Build 9 available from pig Ensembl. We discovered a number of candidate chromosomal regions, and some of them corresponded to QTL regions previously reported. We not only have identified some well-known candidate genes for the traits of interest, such as MC4R (for backfat) and IGF2 (for loin muscle area), but also obtained novel promising genes, including CHCHD3 (for backfat), BMP2 (for loin muscle area, body size and several FL structure traits), and some HOXA family genes (for overall leg action). The candidate regions responsible for body conformation and FL structure soundness did not overlap greatly which implied that these traits were controlled by different genes. Functional clustering analyses classified the genes into categories related to bone and cartilage development, muscle growth and development or the insulin pathway suggesting the traits are regulated by common pathways or gene networks that exert roles at different spatial and temporal stages. This study is one of the earliest GWA reports on important quantitative traits in pigs, and the findings will contribute to the further biological function analysis of the identified candidate genes and potential utilization of them in marker assisted selection.
    PLoS ONE 01/2011; 6(2):e14726. · 3.53 Impact Factor
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    ABSTRACT: Expressed sequence tag (EST) libraries from members of the Penaeidae family and brine shrimp (Artemia franciscana) are currently the primary source of sequence data for shrimp species. Penaeid shrimp are the most commonly farmed worldwide, but selection methods for improving shrimp are limited. A better understanding of shrimp genomics is needed for farmers to use genetic markers to select the best breeding animals. The ESTs from Litopenaeus vannamei have been previously mined for single nucleotide polymorphisms (SNPs). This present study took publicly available ESTs from nine shrimp species, excluding L. vannamei, clustered them with CAP3, predicted SNPs within them using SNPidentifier, and then analyzed whether the SNPs were intra- or interspecies. Major goals of the project were to predict SNPs that may distinguish shrimp species, locate SNPs that may segregate in multiple species, and determine the genetic similarities between L. vannamei and the other shrimp species based on their EST sequences. Overall, 4,597 SNPs were predicted from 4,600 contigs with 703 of them being interspecies SNPs, 735 of them possibly predicting species' differences, and 18 of them appearing to segregate in multiple species. While sequences appear relatively well conserved, SNPs do not appear to be well conserved across shrimp species.
    Animal Biotechnology 04/2010; 21(2):100-3. · 0.88 Impact Factor
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    ABSTRACT: In the past decade, there have been many advances in whole-genome sequencing in domestic animals, as well as the development of "next-generation" sequencing technologies and high-throughput genotyping platforms. Consequently, these advances have led to the creation of the high-density SNP array as a state-of-the-art tool for genetics and genomics analyses of domestic animals. The emergence and utilization of SNP arrays will have significant impacts not only on the scale, speed, and expense of SNP genotyping, but also on theoretical and applied studies of quantitative genetics, population genetics and molecular evolution. The most promising applications in agriculture could be genome-wide association studies (GWAS) and genomic selection for the improvement of economically important traits. However, some challenges still face these applications, such as incorporating linkage disequilibrium (LD) information from HapMap projects, data storage, and especially appropriate statistical analyses on the high-dimensional, structured genomics data. More efforts are still needed to make better use of the high-density SNP arrays in both academic studies and industrial applications.
    Asian Australasian Journal of Animal Sciences 01/2010; 23(7). · 0.64 Impact Factor
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    ABSTRACT: To evaluate the associations between 14 biological candidate genes and scrotal hernias in pigs. 1,534 Pietrain-based pigs, including 692 individuals from 298 pig families and 842 male pigs without family information. Pigs were classified as affected or unaffected for scrotal hernias. Single nucleotide polymorphisms of candidate genes were analyzed via PCR assays and genotyped. Statistical analyses were performed on the family-trio and the case-control data. 2 genes involved in collagen metabolism (homeobox A10 [HOXA10] and matrix metalloproteinases 2 [MMP2]) and 1 gene encoding zinc finger protein multitype 2 (ZFPM2, important in the development of diaphragmatic hernia) were significantly associated with hernias. Pigs with these genotypes had high odds of developing scrotal hernias in the case and control groups (2 ZFPM2 variants: odds ratio, 4.3 [95% confidence interval, 2.78 to 6.64] and 4.45[95%confidenceinterval,2.88to6.88]). Anothergene, collagentypeII A 1(COL2A1),was potentially involved in hernia development. HOXA10, ZFPM2, MMP2, and COL2A1 could have important roles in pig hernia development and potentially be useful for marker-assisted selection in the pig industry. Pigs are used for the study of many human diseases because of their physiologic similarities. Genes associated with scrotal hernias in this study may be directly used in understanding the molecular mechanisms underlying this defect in humans.
    American Journal of Veterinary Research 09/2009; 70(8):1006-12. · 1.35 Impact Factor
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    ABSTRACT: CRP3 is the muscle-specific form of the cysteine and glycine-rich protein family and plays an important role in myofiber differentiation. Here we isolated and characterized its coding gene CSRP3 from porcine muscle. Phylogenic analyses demonstrated that CSRP3 diverged first and is distinguished from two other members, CSRP1 and CSRP2. CSRP3 mRNA was up-regulated during the development of porcine embryonic skeletal muscle, indicating its potential importance in muscle growth. Genetic variant analyses detected multiple variations in an approximately 400 bp region covering exon 4 and its downstream intron, and two haplotypes were identified by sequencing. One of synonymous substitutions C1924T was used for linkage and association analyses. It was revealed that the substitution of C1924T had significant associations with firmness (P < 0.01), Lab Loin pH, Off Flavor Score and Water Holding Capacity (P < 0.05), and a suggestive effect (P < 0.1) on Flavor Score and Average Glycolytic Potential in a Berkshire x Yorkshire F2 population. The association analyses results agreed with the gene's localization to a QTL region for meat quality traits on porcine chromosome 2p14-17 demonstrated by both linkage mapping and RH mapping. These results provide fundamental evidence for CSRP3 as a functional candidate gene affecting pig meat quality.
    Molecular Biology Reports 07/2009; 37(1):451-9. · 2.51 Impact Factor
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    ABSTRACT: Scrotal hernia in pigs is a complex trait likely affected by genetic and environmental factors. A large-scale association analysis of positional and functional candidate genes was conducted in four previously identified genomic regions linked to hernia susceptibility on Sus scrofa chromosomes 2 and 12, as well as the fifth region around 67 cM on chromosome 2, respectively. In total, 151 out of 416 SNPs discovered were genotyped successfully. Using a family-based analysis we found that four regions surrounding ELF5, KIF18A, COL23A1 on chromosome 2, and NPTX1 on chromosome 12, respectively, may contain the genetic variants important for the development of the scrotal hernia in pigs. These findings were replicated in another case-control dataset. The SNPs around the ELF5 region were in high linkage disequilibrium with each other, and a haplotype containing SNPs from ELF5 and CAT was highly significantly associated with hernia development. Extensive re-sequencing work focused on the KIF18A gene did not detect any further SNPs with extensive association signals. These genes may be involved in the estrogen receptor signaling pathway (KIF18A and NPTX1), the epithelial-mesenchymal transition (ELF5) and the collagen metabolism pathway (COL23A1), which are associated with the important molecular characteristics of hernia pathophysiology. Further investigation on the molecular mechanisms of these genes may provide more molecular clues on hernia development in pigs.
    PLoS ONE 02/2009; 4(3):e4837. · 3.53 Impact Factor
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    ABSTRACT: To investigate candidate genes involved in human type 2 diabetes (T2D) for obesity-related phenotypes in pigs. Statistical association analyses of genes with fat deposition were realized in a pig reference family constructed by two breeds, Berkshire and Yorkshire. Extensive sequencing was then attempted to discover the causative polymorphism. Genes implied in human T2D development, TCF7L2, WFS1, FTO, SLC30A8, and GCKR, were mapped on Sus scrofa chromosomes 14, 8, 6, 4, and 3, respectively. Only TCF7L2 was significantly associated with five fat traits in pigs. Further investigation demonstrated that one haplotype (HapB), but not the HapA (homologous to the region for human T2D susceptibility where single-nucleotide polymorphism (SNP) rs7903146 is located), is significantly associated with the fat-related traits. In HapB, two SNPs in TCF7L2 exon 8 and intron 10 are significantly associated with five fat traits, and may be in linkage disequilibrium with the causative variant with additive effects on all four backfat traits, and the total lipid percentage. Pigs of genotype TT for the SNP in exon 8 have only one transcript isoform (the one without exon 4), and lower backfat depth. Candidate gene analyses could provide novel ideas about how these genes function in T2D susceptibility in human, and support that the pig can be a suitable model for human obesity and T2D research. Further replication of this research in other pig populations should be considered, so that the possibility of utilizing these genetic markers in pig breeding or in animal model research can be explored.
    Obesity 01/2009; 17(2):323-9. · 3.92 Impact Factor
  • Bin Fan, Zhi-Qiang Du, Max F Rothschild
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    ABSTRACT: The association of the FTO gene with obesity has been implicated in various human populations. The FTO gene is also most likely involved in the regulation of energy balance and feed intake. Here, the FTO gene was studied as a candidate gene for fatness and growth rate traits in pigs. The amino acid sequence of the FTO gene showed high conservation among human, pig, and other important domestic animals. Twelve variants including ten SNPs and two indels were detected, and then five SNPs within different genomic regions were genotyped in the ISU Berkshire x Yorkshire pig resource family. The linkage disequilibrium analyses revealed that most of these FTO variants were not in strong LD with each other. The SNPs c.46-139A > T within intron 1 and a synonymous mutation c.594C > G (Ala198Ala) within exon 3 had significant (P < 0.01) associations with average daily gain on test and total lipid percentage in muscle, respectively. Five major haplotypes were identified and the subsequent association analyses suggested that haplotype 2 (-CTTGG-) was the most favorable for increased growth rate, while haplotype 1 (-CTACG-) was unfavorably associated with intramuscular fatness traits.
    Animal Biotechnology 01/2009; 20(2):58-70. · 0.88 Impact Factor
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    ABSTRACT: TEA domain transcription factors play vital roles in myogenesis by binding the M-CAT motif in the promoter of the muscle-specific genes. In the present study, we cloned two porcine TEA domain family genes, TEF1 and RTEF1, and identified two different variants respectively. RT-PCR revealed that the TEF1-a variant was highly expressed and up-regulated with the development of the porcine skeletal muscle, indicating its potential regulatory function for muscle development. Promoter analysis revealed porcine TEF1 was regulated, in a TATA-independent manner, by a specific intact initiator element, and numerous binding motifs of multiple transcription factors, including SP1, CREB/ATF and AREB6. A substitution G93A was identified in the 5'-flanking sequence and used for the linkage mapping of TEF1. Association analyses in a BerkshirexYorkshire F(2) population revealed that the substitution of G93A has a significant effect on average daily gain from birth to weaning (p<0.05) and 16-day weight (p<0.05), and a suggestive effect on loin eye area (p<0.06), average back fat (p<0.07) and lumbar back fat (p<0.08). The association analyses results are in agreement with the gene's localization demonstrated by linkage analysis, SCHP and RH mapping to the QTL region of growth and carcass traits on chromosome 2p14-17.
    Comparative Biochemistry and Physiology Part B Biochemistry and Molecular Biology 08/2008; 150(4):447-53. · 2.07 Impact Factor
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    ABSTRACT: The mistyping of the angiotensin I-converting enzyme insertion/deletion (ACE I/D) has been well documented, and new methods have been suggested here to improve the genotyping efficiency. Buccal cell samples were collected from 157 young Caucasians, and genotyped using previously known and newly developed PCR amplification genotyping techniques, as well as PCR-RFLP tests for three single nucleotide polymorphisms (rs4327, rs4341 and rs4343). Inconsistent genotyping results were found when using only the PCR amplification genotyping techniques across repeated attempts (8% to 45%), however, individual SNP genotyping was highly consistent (100%). Two SNPs (rs4341 and rs4343) were in complete LD and SNP rs4327 was in high LD with the ACE I/D. The ACE I/D was in HW equilibrium in the portion of the population with consistent genotyping results, whereas the three SNPs were not in HW equilibrium. The mistyping of ACE I/D by only PCR amplification can be improved using alternative methods.
    Molecular Biology Reports 08/2008; 36(6):1305-10. · 2.51 Impact Factor
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    ABSTRACT: Genetic factors could affect the incidence of scrotal hernia in pigs. To detect genomic regions or genes involved in the development of scrotal hernia, we genotyped 12 affected and 12 control inbred animals using the Porcine 60K Beadchip. After case-control association analyses, using both single marker and Bayesian analyses, we confirmed the involvement of genomic regions on SSC2, SSC5 and SSCX. Homozygosity mapping was also used to detect several possible recessive regions. Given previous reports implicating SSC2 in most studies we selected two candidate genes on SSC2, CTNNA1 and Testican1, and discovered synonymous SNPs in exonic regions and 3’-untraslated regions. However, no apparent causative mutations were found. Further investigation on the structural variation and functional importance of these genes and regions is still needed.
    International Plant and Animal Genome Conference XX 2012;
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    ABSTRACT: MicroRNA (miRNA) are known to influence the mRNA and protein abundance through post-transcriptional gene regulation following interactions with the 3′UTR that lead to translation inhibition and/or mRNA degradation. Reproductive tissues are comprised of dynamic cell types that undergo significant transcriptional and translational reorganization during gamete development, embryogenesis, during conceptus elongation and over the course of the estrous cycle and early pregnancy. We utilized massively parallel deep sequencing using the SOLiD sequencing system to characterize small RNA expression in the maturing cumulus oocyte complex, early embryo development, elongating conceptus and in the uterine endometrium during the estrous cycle and early pregnancy in pigs. Numerous miRNA, piRNA and other small RNA molecules were identified and mapped them to the pig genome. Following mapping and quantification of small RNA sequence reads, unique miRNA and piRNA clusters were identified in addition to multiple miRNA that are replicated throughout the genome. Changes in total small RNA predicted to interact with specific mRNA were used to identify potential PTGR events in the oocyte following germinal vesicle breakdown in the oocyte during maturation. Functional characterization of MIR21 and its ability to regulate two potential targets mRNA, PDCD4 and PTEN, was conducted in the maturing cumulus oocyte complex. Increased MIR21 expression during oocyte maturation is temporally associated with the PDCD4 protein suppression which was inhibited in the presence of an anti-MIR21 oligonucleotide. This project was supported by National Research Initiative Competitive Grant no. 2008-35205-05309 and 2008-35205-18712 from the USDA National Institute of Food and Agriculture.
    International Plant and Animal Genome Conference XX 2012;