-
[show abstract]
[hide abstract]
ABSTRACT: A resource that provides candidate transcription factor binding sites (TFBSs) does not currently exist for cattle. Such data is necessary, as predicted sites may serve as excellent starting locations for future omics studies to develop transcriptional regulation hypotheses. In order to generate this resource, we employed a phylogenetic footprinting approach-using sequence conservation across cattle, human and dog-and position-specific scoring matrices to identify 379,333 putative TFBSs upstream of nearly 8000 Mammalian Gene Collection (MGC) annotated genes within the cattle genome. Comparisons of our predictions to known binding site loci within the PCK1, ACTA1 and G6PC promoter regions revealed 75% sensitivity for our method of discovery. Additionally, we intersected our predictions with known cattle SNP variants in dbSNP and on the Illumina BovineHD 770k and Bos 1 SNP chips, finding 7534, 444 and 346 overlaps, respectively. Due to our stringent filtering criteria, these results represent high quality predictions of putative TFBSs within the cattle genome. All binding site predictions are freely available at http://bfgl.anri.barc.usda.gov/BovineTFBS/ or http://199.133.54.77/BovineTFBS.
Genomics Proteomics & Bioinformatics 02/2013;
-
[show abstract]
[hide abstract]
ABSTRACT: Histone modification has emerged as a very important mechanism regulating the transcriptional status of the genome. Insulin-like growth factor 2 (IGF2) is a peptide hormone controlling various cellular processes, including proliferation and apoptosis. H19 gene is closely linked to IGF2 gene, and IGF2 and H19 are reciprocally regulated imprinted genes. The epigenetic signature of H19 promoter (hypermethylation) on the paternal allele plays a vital role in allowing the expression of the paternal allele of IGF2.46 Our previous studies demonstrate that butyrate regulates the expression of IGF2 as well as genes encoding IGF Binding proteins. To obtain further understanding of histone modification and its regulatory potentials in controlling IGF2/H19 gene expression, we investigated the histone modification status of some key histones associated with the expression of IGF2/H19 genes in bovine cells using RNA-seq in combination with Chip-seq technology. A high-resolution map of the major chromatin modification at the IGF2/H19 locus induced by butyrate was constructed to illustrate the fundamental association of the chromatin modification landscape that may play a role in the activation of the IGF2 gene. High-definition epigenomic landscape mapping revealed that IGF2 and H19 have distinct chromatin modification patterns at their coding and promoter regions, such as TSSs and TTSs. Moreover, the correlation between the differentially methylated regions (DMRs) of IGF2/H19 locus and histone modification (acetylation and methylation) indicated that epigenetic signatures/markers of DNA methylation, histone methylation and histone acetylation were differentially distributed on the expressed IGF2 and silenced H19 genes. Our evidence also suggests that butyrate-induced regional changes of histone acetylation statusin the upstream regulation domain of H19 may be related to the reduced expression of H19 and strong activation of IGF2. Our results provided insights into the mechanism of butyrate-induced loss of imprinting (LOI) of IGF2 and regulation of gene expression by histone modification.
Gene regulation and systems biology 01/2013; 7:57-70.
-
[show abstract]
[hide abstract]
ABSTRACT: Genomic structural variation is an important and abundant source of genetic and phenotypic variation. In this study, we performed an initial analysis of copy number variations (CNVs) using BovineHD SNP genotyping data from 147 Holstein cows identified as having high or low feed efficiency as estimated by residual feed intake (RFI). We detected 443 candidate CNV regions (CNVRs) that represent 18.4 Mb (0.6 %) of the genome. To investigate the functional impacts of CNVs, we created two groups of 30 individual animals with extremely low or high estimated breeding values (EBVs) for RFI, and referred to these groups as low intake (LI; more efficient) or high intake (HI; less efficient), respectively. We identified 240 (~9.0 Mb) and 274 (~10.2 Mb) CNVRs from LI and HI groups, respectively. Approximately 30-40 % of the CNVRs were specific to the LI group or HI group of animals. The 240 LI CNVRs overlapped with 137 Ensembl genes. Network analyses indicated that the LI-specific genes were predominantly enriched for those functioning in the inflammatory response and immunity. By contrast, the 274 HI CNVRs contained 177 Ensembl genes. Network analyses indicated that the HI-specific genes were particularly involved in the cell cycle, and organ and bone development. These results relate CNVs to two key variables, namely immune response and organ and bone development. The data indicate that greater feed efficiency relates more closely to immune response, whereas cattle with reduced feed efficiency may have a greater capacity for organ and bone development.
Functional & Integrative Genomics 09/2012; · 3.83 Impact Factor
-
Yali Hou,
Derek M Bickhart,
Miranda L Hvinden,
Congjun Li,
Jiuzhou Song,
Didier A Boichard,
Sébastien Fritz,
André Eggen,
Sue Denise,
George R Wiggans,
Tad S Sonstegard,
Curtis P Van Tassell, George E Liu
[show abstract]
[hide abstract]
ABSTRACT: BACKGROUND: Btau_4.0 and UMD3.1 are two distinct cattle reference genome assemblies. In our previous study using the low density BovineSNP50 array, we reported a copy number variation (CNV) analysis on Btau_4.0 with 521 animals of 21 cattle breeds, yielding 682 CNV regions with a total length of 139.8 megabases. RESULTS: In this study using the high density BovineHD SNP array, we performed high resolution CNV analyses on both Btau_4.0 and UMD3.1 with 674 animals of 27 cattle breeds. We first compared CNV results derived from these two different SNP array platforms on Btau_4.0. With two thirds of the animals shared between studies, on Btau_4.0 we identified 3,346 candidate CNV regions representing 142.7 megabases (~4.70%) of the genome. With a similar total length but 5 times more event counts, the average CNVR length of current Btau_4.0 dataset is significantly shorter than the previous one (42.7kb vs. 205 kb). Although subsets of these two results overlapped, 64% (91.6 megabases) of current dataset was not present in the previous study. We also performed similar analyses on UMD3.1 using these BovineHD SNP array results. Approximately 50% more and 20% longer CNVs were called on UMD3.1 as compared to those on Btau_4.0. However, a comparable result of CNVRs (3,438 regions with a total length 146.9 megabases) was obtained. We suspect that these results are due to that UMD3.1's efforts of placing unplaced contigs and removing unmerged alleles. Selected CNVs were further experimentally validated, achieving a 73% PCR validation rate, which is considerably higher than the previous validation rate. About 20-45% of CNV regions overlapped with cattle RefSeq genes and Ensembl genes. Panther and IPA analyses indicated that these genes provide a wide spectrum of biological processes involving immune system, lipid metabolism, cell, organism and system development. CONCLUSION: We present a comprehensive result of cattle CNVs at a higher resolution and sensitivity. We identified over 3,000 candidate CNV regions on both Btau_4.0 and UMD3.1, further compared current datasets with previous results, and examined the impacts of genome assemblies on CNV calling.
BMC Genomics 08/2012; 13(1):376. · 4.07 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Copy number variations (CNVs) are gains and losses of genomic sequence greater than 50 bp between two individuals of a species. While single nucleotide polymorphisms (SNPs) are more frequent, CNVs impact a higher percentage of genomic sequence and have potentially greater effects, including the changing of gene structure and dosage, altering gene regulation and exposing recessive alleles. In particular, segmental duplications (SDs) were shown to be one of the catalysts and hotspots for CNV formation. Substantial progress has been made in understanding CNVs in mammals, especially in humans and rodents. CNVs have been shown to be important in both normal phenotypic variability and disease susceptibility. Recently, interest in CNV study has extended into domesticated animals, including cattle. Multiple genome-wide cattle CNV studies have been carried out using both microarray and next generation sequencing technologies. Integration of SD and CNV results with SNP and other datasets are beginning to reveal impacts of CNVs on cattle domestication, health, and production traits.
Functional & Integrative Genomics 07/2012; · 3.83 Impact Factor
-
Derek M Bickhart,
Yali Hou,
Steven G Schroeder,
Can Alkan,
Maria Francesca Cardone,
Lakshmi K Matukumalli,
Jiuzhou Song,
Robert D Schnabel,
Mario Ventura,
Jeremy F Taylor,
Jose Fernando Garcia,
Curtis P Van Tassell,
Tad S Sonstegard,
Evan E Eichler, George E Liu
[show abstract]
[hide abstract]
ABSTRACT: Copy number variations (CNVs) affect a wide range of phenotypic traits; however, CNVs in or near segmental duplication regions are often intractable. Using a read depth approach based on next-generation sequencing, we examined genome-wide copy number differences among five taurine (three Angus, one Holstein, and one Hereford) and one indicine (Nelore) cattle. Within mapped chromosomal sequence, we identified 1265 CNV regions comprising ~55.6-Mbp sequence--476 of which (~38%) have not previously been reported. We validated this sequence-based CNV call set with array comparative genomic hybridization (aCGH), quantitative PCR (qPCR), and fluorescent in situ hybridization (FISH), achieving a validation rate of 82% and a false positive rate of 8%. We further estimated absolute copy numbers for genomic segments and annotated genes in each individual. Surveys of the top 25 most variable genes revealed that the Nelore individual had the lowest copy numbers in 13 cases (~52%, χ(2) test; P-value <0.05). In contrast, genes related to pathogen- and parasite-resistance, such as CATHL4 and ULBP17, were highly duplicated in the Nelore individual relative to the taurine cattle, while genes involved in lipid transport and metabolism, including APOL3 and FABP2, were highly duplicated in the beef breeds. These CNV regions also harbor genes like BPIFA2A (BSP30A) and WC1, suggesting that some CNVs may be associated with breed-specific differences in adaptation, health, and production traits. By providing the first individualized cattle CNV and segmental duplication maps and genome-wide gene copy number estimates, we enable future CNV studies into highly duplicated regions in the cattle genome.
Genome Research 02/2012; 22(4):778-90. · 13.61 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Genomic structural variation is an important and abundant source of genetic and phenotypic variation. We previously reported an initial analysis of copy number variations (CNVs) in Angus cattle selected for resistance or susceptibility to gastrointestinal nematodes. In this study, we performed a large-scale analysis of CNVs using SNP genotyping data from 472 animals of the same population. We detected 811 candidate CNV regions, which represent 141.8 Mb (~4.7%) of the genome. To investigate the functional impacts of CNVs, we created 2 groups of 100 individual animals with extremely low or high estimated breeding values of eggs per gram of feces and referred to these groups as parasite resistant (PR) or parasite susceptible (PS), respectively. We identified 297 (~51 Mb) and 282 (~48 Mb) CNV regions from PR and PS groups, respectively. Approximately 60% of the CNV regions were specific to the PS group or PR group of animals. Selected PR- or PS-specific CNVs were further experimentally validated by quantitative PCR. A total of 297 PR CNV regions overlapped with 437 Ensembl genes enriched in immunity and defense, like WC1 gene which uniquely expresses on gamma/delta T cells in cattle. Network analyses indicated that the PR-specific genes were predominantly involved in gastrointestinal disease, immunological disease, inflammatory response, cell-to-cell signaling and interaction, lymphoid tissue development, and cell death. By contrast, the 282 PS CNV regions contained 473 Ensembl genes which are overrepresented in environmental interactions. Network analyses indicated that the PS-specific genes were particularly enriched for inflammatory response, immune cell trafficking, metabolic disease, cell cycle, and cellular organization and movement.
Functional & Integrative Genomics 09/2011; 12(1):81-92. · 3.83 Impact Factor
-
George E Liu
[show abstract]
[hide abstract]
ABSTRACT: Next-generation DNA sequencing technologies are able to produce millions of short sequence reads in a highthroughput, cost-effective fashion. The emergence of these technologies has not only facilitated genome sequencing but also changed the landscape of life sciences. This review surveys their recent applications in food, nutrition and agriculture ranging from whole-genome sequencing and resequencing, RNA-seq and ChIP-seq, structural, functional and comparative genomics to metagenomics and epigenetics. We already began to witness broad impacts of these DNA sequencing technologies for solving the complex biological problems in food, nutrition and agriculture. In this article, recent patent-based information is also included.
Recent patents on food, nutrition & agriculture. 08/2011; 3(3):187-95.
-
George E Liu,
Twain Brown,
Deborah A Hebert,
Maria Francesca Cardone,
Yali Hou,
Ratan K Choudhary,
Jessica Shaffer,
Chinwendu Amazu,
Erin E Connor,
Mario Ventura,
Louis C Gasbarre
[show abstract]
[hide abstract]
ABSTRACT: Genomic structural variation is an important and abundant source of genetic and phenotypic variation. We report an initial analysis of copy number variations (CNVs) in cattle selected for resistance or susceptibility to intestinal nematodes. We performed three array comparative genomic hybridization (CGH) experiments to compare Angus cattle with extreme phenotypes for fecal egg count and serum pepsinogen level. We identified 20 CNVs in total, of which 12 were within known chromosomes harboring or adjacent to gains or losses. About 85% of the CNV identified (17/20) overlapped with cattle CNV regions that were reported recently. Selected CNVs were further validated by independent methods using quantitative PCR (qPCR) and FISH. Pathway analyses indicated that annotated cattle genes within these variable regions are particularly enriched for immune function affecting receptor activities, signal transduction, and transcription. Analysis of transcription factor binding sites (TFBS) within the promoter regions of differentially expressed genes suggested that common transcription factors are probably involved in parasite resistance. These results provide valuable hypotheses for the future study of cattle CNVs underlying economically important health and production traits.
Mammalian Genome 02/2011; 22(1-2):111-21. · 2.89 Impact Factor
-
Yali Hou, George E Liu,
Derek M Bickhart,
Maria Francesca Cardone,
Kai Wang,
Eui-Soo Kim,
Lakshmi K Matukumalli,
Mario Ventura,
Jiuzhou Song,
Paul M VanRaden,
Tad S Sonstegard,
Curt P Van Tassell
[show abstract]
[hide abstract]
ABSTRACT: Copy number variation (CNV) represents another important source of genetic variation complementary to single nucleotide polymorphism (SNP). High-density SNP array data have been routinely used to detect human CNVs, many of which have significant functional effects on gene expression and human diseases. In the dairy industry, a large quantity of SNP genotyping results are becoming available and can be used for CNV discovery to understand and accelerate genetic improvement for complex traits.
We performed a systematic analysis of CNV using the Bovine HapMap SNP genotyping data, including 539 animals of 21 modern cattle breeds and 6 outgroups. After correcting genomic waves and considering the pedigree information, we identified 682 candidate CNV regions, which represent 139.8 megabases (~4.60%) of the genome. Selected CNVs were further experimentally validated and we found that copy number "gain" CNVs were predominantly clustered in tandem rather than existing as interspersed duplications. Many CNV regions (~56%) overlap with cattle genes (1,263), which are significantly enriched for immunity, lactation, reproduction and rumination. The overlap of this new dataset and other published CNV studies was less than 40%; however, our discovery of large, high frequency (> 5% of animals surveyed) CNV regions showed 90% agreement with other studies. These results highlight the differences and commonalities between technical platforms.
We present a comprehensive genomic analysis of cattle CNVs derived from SNP data which will be a valuable genomic variation resource. Combined with SNP detection assays, gene-containing CNV regions may help identify genes undergoing artificial selection in domesticated animals.
BMC Genomics 02/2011; 12:127. · 4.07 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Transgenic cattle carrying multiple genomic modifications have been produced by serial rounds of somatic cell chromatin transfer (cloning) of sequentially genetically targeted somatic cells. However, cloning efficiency tends to decline with the increase of rounds of cloning. It is possible that multiple rounds of cloning compromise the genome integrity or/and introduce epigenetic errors in the resulting cell lines, rendering a decline in cloning. To test these possibilities, we performed 9 high density array Comparative Genomic Hybridization (CGH) experiments to test the genome integrity in 3 independent bovine transgenic cell lineages generated from genetic modification and cloning. Our plan included the control hybridizations (self to self) of the 3 founder cell lines and 6 comparative hybridizations between these founders and their derived cell lines with either high or low cloning efficiencies.
We detected similar amounts of differences between the control hybridizations (8, 13 and 39 differences) and the comparative analyses of both "high" and "low" cell lines (ranging from 7 to 57 with a mean of ~20). Almost 75% of the large differences (>10 kb) and about 45% of all differences shared the same type (loss or gain) and were located in nearby genomic regions across hybridizations. Therefore, it is likely that they were not true differences but caused by systematic factors associated with local genomic features (e.g. GC contents).
Our findings reveal that large copy number variations are less likely to arise during genetic targeting and serial rounds of cloning, fortifying the notion that epigenetic errors introduced from serial cloning may be responsible for the cloning efficiency decline.
Genome integrity. 01/2011; 2(1):6.
-
George E Liu,
Yali Hou,
Bin Zhu,
Maria Francesca Cardone,
Lu Jiang,
Angelo Cellamare,
Apratim Mitra,
Leeson J Alexander,
Luiz L Coutinho,
Maria Elena Dell'Aquila, [......],
Dan Nonneman,
Luciana C de A Regitano,
Tim P L Smith,
Jiuzhou Song,
Tad S Sonstegard,
Curt P Van Tassell,
Mario Ventura,
Evan E Eichler,
Tara G McDaneld,
John W Keele
[show abstract]
[hide abstract]
ABSTRACT: Genomic structural variation is an important and abundant source of genetic and phenotypic variation. Here, we describe the first systematic and genome-wide analysis of copy number variations (CNVs) in modern domesticated cattle using array comparative genomic hybridization (array CGH), quantitative PCR (qPCR), and fluorescent in situ hybridization (FISH). The array CGH panel included 90 animals from 11 Bos taurus, three Bos indicus, and three composite breeds for beef, dairy, or dual purpose. We identified over 200 candidate CNV regions (CNVRs) in total and 177 within known chromosomes, which harbor or are adjacent to gains or losses. These 177 high-confidence CNVRs cover 28.1 megabases or approximately 1.07% of the genome. Over 50% of the CNVRs (89/177) were found in multiple animals or breeds and analysis revealed breed-specific frequency differences and reflected aspects of the known ancestry of these cattle breeds. Selected CNVs were further validated by independent methods using qPCR and FISH. Approximately 67% of the CNVRs (119/177) completely or partially span cattle genes and 61% of the CNVRs (108/177) directly overlap with segmental duplications. The CNVRs span about 400 annotated cattle genes that are significantly enriched for specific biological functions, such as immunity, lactation, reproduction, and rumination. Multiple gene families, including ULBP, have gone through ruminant lineage-specific gene amplification. We detected and confirmed marked differences in their CNV frequencies across diverse breeds, indicating that some cattle CNVs are likely to arise independently in breeds and contribute to breed differences. Our results provide a valuable resource beyond microsatellites and single nucleotide polymorphisms to explore the full dimension of genetic variability for future cattle genomic research.
Genome Research 03/2010; 20(5):693-703. · 13.61 Impact Factor
-
Jianqi Yang,
Xiaoying Kong,
Maria Emilia S Martins-Santos,
Gabriela Aleman,
Ernestine Chaco, George E Liu,
Shwu-Yuan Wu,
David Samols,
Parvin Hakimi,
Cheng-Ming Chiang,
Richard W Hanson
[show abstract]
[hide abstract]
ABSTRACT: The SIRT1 activators isonicotinamide (IsoNAM), resveratrol, fisetin, and butein repressed transcription of the gene for the cytosolic form of phosphoenolpyruvate carboxykinase (GTP) (PEPCK-C). An evolutionarily conserved binding site for hepatic nuclear factor (HNF) 4alpha (-272/-252) was identified, which was required for transcriptional repression of the PEPCK-C gene promoter caused by these compounds. This site contains an overlapping AP-1 binding site and is adjacent to the C/EBP binding element (-248/-234); the latter is necessary for hepatic transcription of PEPCK-C. AP-1 competed with HNF4alpha for binding to this site and also decreased HNF4alpha stimulation of transcription from the PEPCK-C gene promoter. Chromatin immunoprecipitation experiments demonstrated that HNF4alpha and AP-1, but not C/EBPbeta, reciprocally bound to this site prior to and after treating HepG2 cells with IsoNAM. IsoNAM treatment resulted in deacetylation of HNF4alpha, which decreased its binding affinity to the PEPCK-C gene promoter. In HNF4alpha-null Chinese hamster ovary cells, IsoNAM and resveratrol failed to repress transcription from the PEPCK-C gene promoter; overexpression of HNF4alpha in Chinese hamster ovary cells re-established transcriptional inhibition. Exogenous SIRT1 expression repressed transcription, whereas knockdown of SIRT1 by RNA interference reversed this effect. IsoNAM decreased the level of mRNA for PEPCK-C but had no effect on mRNA for glucose-6-phosphatase in AML12 mouse hepatocytes. We conclude that SIRT1 activation inhibited transcription of the gene for PEPCK-C in part by deacetylation of HNF4alpha. However, SIRT1 deacetylation of other key regulatory proteins that control PEPCK-C gene transcription also likely contributed to the inhibitory effect.
Journal of Biological Chemistry 09/2009; 284(40):27042-53. · 4.77 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Using bacteria artificial chromosome (BAC) end sequences (16.9 Mb) and high-quality alignments of genomic sequences (17.4 Mb), we performed a global assessment of the divergence distributions, phylogenies, and consensus sequences for Alu elements in primates including lemur, marmoset, macaque, baboon, and chimpanzee as compared to human. We found that in lemurs, Alu elements show a broader and more symmetric sequence divergence distribution, suggesting a steady rate of Alu retrotransposition activity among prosimians. In contrast, Alu elements in anthropoids show a skewed distribution shifted toward more ancient elements with continual declining rates in recent Alu activity along the hominoid lineage of evolution. Using an integrated approach combining mutation profile and insertion/deletion analyses, we identified nine novel lineage-specific Alu subfamilies in lemur (seven), marmoset (one), and baboon/macaque (one) containing multiple diagnostic mutations distinct from their human counterparts-Alu J, S, and Y subfamilies, respectively. Among these primates, we show that that the lemur has the lowest density of Alu repeats (55 repeats/Mb), while marmoset has the greatest abundance (188 repeats/Mb). We estimate that approximately 70% of lemur and 16% of marmoset Alu elements belong to lineage-specific subfamilies. Our analysis has provided an evolutionary framework for further classification and refinement of the Alu repeat phylogeny. The differences in the distribution and rates of Alu activity have played an important role in subtly reshaping the structure of primate genomes. The functional consequences of these changes among the diverse primate lineages over such short periods of evolutionary time are an important area of future investigation.
Genome Research 06/2009; 19(5):876-85. · 13.61 Impact Factor
-
Christine G Elsik,
Ross L Tellam,
Kim C Worley,
Richard A Gibbs,
Donna M Muzny,
George M Weinstock,
David L Adelson,
Evan E Eichler,
Laura Elnitski,
Roderic Guigó, [......],
Ashley J Waardenberg,
Zhiquan Wang,
Robert Ward,
Rosemarie Weikard,
Thomas H Welsh,
Stephen N White,
Laurens G Wilming,
Kris R Wunderlich,
Jianqi Yang,
Feng-Qi Zhao
[show abstract]
[hide abstract]
ABSTRACT: To understand the biology and evolution of ruminants, the cattle genome was sequenced to about sevenfold coverage. The cattle genome contains a minimum of 22,000 genes, with a core set of 14,345 orthologs shared among seven mammalian species of which 1217 are absent or undetected in noneutherian (marsupial or monotreme) genomes. Cattle-specific evolutionary breakpoint regions in chromosomes have a higher density of segmental duplications, enrichment of repetitive elements, and species-specific variations in genes associated with lactation and immune responsiveness. Genes involved in metabolism are generally highly conserved, although five metabolic genes are deleted or extensively diverged from their human orthologs. The cattle genome sequence thus provides a resource for understanding mammalian evolution and accelerating livestock genetic improvement for milk and meat production.
Science 05/2009; 324(5926):522-8. · 31.20 Impact Factor
-
Richard A Gibbs,
Jeremy F Taylor,
Curtis P Van Tassell,
William Barendse,
Kellye A Eversole,
Clare A Gill,
Ronnie D Green,
Debora L Hamernik,
Steven M Kappes,
Sigbjørn Lien, [......],
Riccardo Negrini,
Mike E Goddard,
Ben J Hayes,
Daniel G Bradley,
Marcos Barbosa da Silva,
Lilian P L Lau, George E Liu,
David J Lynn,
Francesca Panzitta,
Ken G Dodds
[show abstract]
[hide abstract]
ABSTRACT: The imprints of domestication and breed development on the genomes of livestock likely differ from those of companion animals. A deep draft sequence assembly of shotgun reads from a single Hereford female and comparative sequences sampled from six additional breeds were used to develop probes to interrogate 37,470 single-nucleotide polymorphisms (SNPs) in 497 cattle from 19 geographically and biologically diverse breeds. These data show that cattle have undergone a rapid recent decrease in effective population size from a very large ancestral population, possibly due to bottlenecks associated with domestication, selection, and breed formation. Domestication and artificial selection appear to have left detectable signatures of selection within the cattle genome, yet the current levels of diversity within breeds are at least as great as exists within humans.
Science 05/2009; 324(5926):528-32. · 31.20 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Brain-derived neurotrophic factor (BDNF) has multiple alternative splicing variants and plays diverse biological functions in mammals, including neuronal survival, cholesterol metabolism, cell differentiation and tumor development. However, genomic structures of chicken BDNF (cBDNF) variants and its potential functions are still undefined. Here, we characterized two novel alternative splicing variants of cBDNF, cBDNF1 and cBDNF2, via combining comparative genomics methods and molecular techniques in inbred chicken line 6(3) and line 7(2), which have been developed to be resistant and susceptible, respectively, to Marek's disease tumor since 1939. Both cBDNFs consist of a bipartite transcript, with different 5' exons, exon I (298 bp) in cBDNF1 and exon II (286 bp) in cBDNF2, each of which is spliced to the common 3' exon IV. Exon I and IV are highly conserved between chicken and mammals, whereas exon II is unique for chicken. The amino acid sequence of cBDNF1 contains 8 additional amino acids in the N terminal compared to cBDNF2. cBDNF1 and cBDNF2 were only expressed in the hypothalamus among eight tissues, and cBDNF2 showed lower expression than that of cBDNF1 in both lines. The expression level of cBDNF1 was significantly higher in line 7(2) than in line 6(3) (P<0.01). Notably, the DNA methylation levels on the cis-regulatory region of cBDNF1 was negatively correlated with its expression level, which suggests that the mRNA expression level of cBDNF1 may be related to the DNA methylation status in the chickens. We also discussed a potential role of variant cBDNF1 in MD tumor resistance and susceptibility.
Brain research 03/2009; 1269:1-10. · 2.46 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: A systematic phylogenetic footprinting approach was performed to identify conserved transcription factor binding sites (TFBSs) in mammalian promoter regions using human, mouse and rat sequence alignments. We found that the score distributions of most binding site models did not follow the Gaussian distribution required by many statistical methods. Therefore, we performed an empirical test to establish the optimal threshold for each model. We gauged our computational predictions by comparing with previously known TFBSs in the PCK1 gene promoter of the cytosolic isoform of phosphoenolpyruvate carboxykinase, and achieved a sensitivity of 75% and a specificity of approximately 32%. Almost all known sites overlapped with predicted sites, and several new putative TFBSs were also identified. We validated a predicted SP1 binding site in the control of PCK1 transcription using gel shift and reporter assays. Finally, we applied our computational approach to the prediction of putative TFBSs within the promoter regions of all available RefSeq genes. Our full set of TFBS predictions is freely available at http://bfgl.anri.barc.usda.gov/tfbsConsSites.
Genomics Proteomics & Bioinformatics 01/2009; 6(3-4):129-43.
-
[show abstract]
[hide abstract]
ABSTRACT: Chicken Repeat 1 (CR1) repeats are the most abundant family of repeats in the chicken genome, with more than 200,000 copies accounting for approximately 80% of the chicken interspersed repeats. CR1 repeats are believed to have arisen from the retrotransposition of a small number of master elements, which gave rise to the 22 CR1 subfamilies as previously reported in Repbase. We performed a global assessment of the divergence distributions, phylogenies, and consensus sequences of CR1 repeats in the chicken genome. We identified and validated 57 chicken CR1 subfamilies and further analyzed the correlation between these subfamilies and their regional GC contents. We also discovered one novel lineage-specific CR1 subfamilies in turkeys when compared with chickens. We built an evolutionary tree of these subfamilies and concluded that CR1 repeats may play an important role in reshaping the structure of bird genomes.
Genome Biology and Evolution 01/2009; 1:119-30. · 4.62 Impact Factor
-
George E Liu
[show abstract]
[hide abstract]
ABSTRACT: The next-generation sequencing technologies are able to produce millions of short sequence reads in a high-throughput, cost-effective fashion. The emergence of these technologies has not only facilitated genome sequencing but also started to change the landscape of life sciences. Here, I survey their major applications ranging from whole-genome sequencing and resequencing, single nucleotide polymorphism (SNP) and structural variation discovery, to mRNA and noncoding RNA profiling and protein-nucleic acid interaction assay. These case studies in structural, functional and comparative genomics, metagenomics, and epigenomics are providing a more complete picture of the genome structures and functions. In the near future, we will witness broad impacts of these next-generation sequencing technologies for solving the complex biological problems in food, nutrition and agriculture. In this article, recent patents based information is also included.
Recent patents on food, nutrition & agriculture. 01/2009; 1(1):75-9.
