Publications by authors named "Hasan Khatib"

41 Publications

Prediction of biological age and evaluation of genome-wide dynamic methylomic changes throughout human aging.

G3 (Bethesda) 2021 Apr 7. Epub 2021 Apr 7.

Department of Animal and Dairy Sciences, University of Wisconsin-Madison, 53706, Madison, WI, USA.

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 4,409 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/g3journal/jkab112DOI Listing
April 2021

The Intergenerational Impacts of Paternal Diet on DNA Methylation and Offspring Phenotypes in Sheep.

Front Genet 2020 5;11:597943. Epub 2020 Nov 5.

Department of Animal and Dairy Sciences, University of Wisconsin-Madison, Madison, WI, United States.

Knowledge of non-genomic inheritance of traits is currently limited. Although it is well established that maternal diet influences offspring inheritance of traits through DNA methylation, studies on the impact of prepubertal paternal diet on DNA methylation are rare. This study aimed to evaluate the impact of prepubertal diet in Polypay rams on complex traits, DNA methylation, and transmission of traits to offspring. A total of 10 littermate pairs of F0 rams were divided so that one ram was fed a control diet, and the other was fed the control diet with supplemental methionine. Diet was associated with earlier age at puberty in treatment vs. control F0 rams. F0 treatment rams tended to show decreased pubertal weight compared to control rams; however, no differences were detected in overall growth. A total of ten F0 rams were bred, and the entire F1 generation was fed a control diet. Diet of F0 rams had a significant association with scrotal circumference (SC) and weight at puberty of F1 offspring. The paternal diet was not significantly associated with F1 ram growth or age at puberty. The DNA methylation of F0 ram sperm was assessed, and genes related to both sexual development (e.g., , , , , , ) and body weight (e.g., , ) were prevalent in the data. These results provide novel information about the mechanisms through which the prepubertal paternal diet may alter body weight at puberty and sexual development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fgene.2020.597943DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7674940PMC
November 2020

Integration of whole-genome DNA methylation data with RNA sequencing data to identify markers for bull fertility.

Anim Genet 2020 Aug 23;51(4):502-510. Epub 2020 Apr 23.

Department of Animal Sciences, University of Wisconsin, Madison, WI, 53706, USA.

Predicting bull fertility prior to breeding is a current challenge for the dairy industry. The use of molecular biomarkers has been previously assessed. However, the integration of this information has not been performed to extract biologically relevant markers. The goal of this study was to integrate DNA methylation data with previously published RNA-sequencing results in order to identify candidate markers for sire fertility. A total of 1765 differentially methylated cytosines were found between high- and low-fertility sires. Ten genes associated with 11 differentially methylated cytosines were found in a previous study of gene expression between high- and low-fertility sires. Additionally, two of these genes code for proteins found exclusively in bull seminal plasma. Collectively, our results reveal 10 genes that could be used in the future as a panel for predicting bull fertility.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/age.12941DOI Listing
August 2020

Characterization and functional roles of paternal RNAs in 2-4 cell bovine embryos.

Sci Rep 2019 12 30;9(1):20347. Epub 2019 Dec 30.

University of Wisconsin, Department of Animal Sciences, Madison, WI, 53706, USA.

Embryos utilize oocyte-donated RNAs until they become capable of producing RNAs through embryonic genome activation (EGA). The sperm's influence over pre-EGA RNA content of embryos remains unknown. Recent studies have revealed that sperm donate non-genomic components upon fertilization. Thus, sperm may also contribute to RNA presence in pre-EGA embryos. The first objective of this study was to investigate whether male fertility status is associated with the RNAs present in the bovine embryo prior to EGA. A total of 65 RNAs were found to be differentially expressed between 2-4 cell bovine embryos derived from high and low fertility sires. Expression patterns were confirmed for protein phosphatase 1 regulatory subunit 36 (PPP1R36) and ataxin 2 like (ATXN2L) in three new biological replicates. The knockdown of ATXN2L led to a 22.9% increase in blastocyst development. The second objective of this study was to characterize the parental origin of RNAs present in pre-EGA embryos. Results revealed 472 sperm-derived RNAs, 2575 oocyte-derived RNAs, 2675 RNAs derived from both sperm and oocytes, and 663 embryo-exclusive RNAs. This study uncovers an association of male fertility with developmentally impactful RNAs in 2-4 cell embryos. This study also provides an initial characterization of paternally-contributed RNAs to pre-EGA embryos. Furthermore, a subset of 2-4 cell embryo-specific RNAs was identified.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-019-55868-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6937301PMC
December 2019

Melatonin promotes Cashmere goat (Capra hircus) secondary hair follicle growth: a view from integrated analysis of long non-coding and coding RNAs.

Cell Cycle 2018 17;17(10):1255-1267. Epub 2018 Jul 17.

a College of Animal Science & Technology , Northwest A&F University , Yangling , China.

The role of melatonin in promoting the yield of Cashmere goat wool has been demonstrated for decades though there remains a lack of knowledge regarding melatonin mediated hair follicle growth. Recent studies have demonstrated that long non-coding RNAs (lncRNAs) are widely transcribed in the genome and play ubiquitous roles in regulating biological processes. However, the role of lncRNAs in regulating melatonin mediated hair follicle growth remains unclear. In this study, we established an in vitro Cashmere goat secondary hair follicle culture system, and demonstrated that 500 ng/L melatonin exposure promoted hair follicle fiber growth. Based on long intergenic RNA sequencing, we demonstrated that melatonin promoted hair follicle elongation via regulating genes involved in focal adhesion and extracellular matrix receptor pathways and further cis predicting of lncRNAs targeted genes indicated that melatonin mediated lncRNAs mainly targeted vascular smooth muscle contraction and signaling pathways regulating the pluripotency of stem cells. We proposed that melatonin exposure not only perturbed key signals secreted from hair follicle stem cells to regulate hair follicle development, but also mediated lncRNAs mainly targeted to pathways involved in the microvascular system and extracellular matrix, which constitute the highly orchestrated microenvironment for hair follicle stem cell. Taken together, our findings here provide a profound view of lncRNAs in regulating Cashmere goat hair follicle circadian rhythms and broaden our knowledge on melatonin mediated hair follicle morphological changes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/15384101.2018.1471318DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6110581PMC
November 2019

Integrative analysis of methylomic and transcriptomic data in fetal sheep muscle tissues in response to maternal diet during pregnancy.

BMC Genomics 2018 02 6;19(1):123. Epub 2018 Feb 6.

Department of Animal Sciences, University of Wisconsin, 1675 Observatory Drive, Madison, WI, 53706, USA.

Background: Numerous studies have established a link between maternal diet and the physiological and metabolic phenotypes of their offspring. In previous studies in sheep, we demonstrated that different maternal diets altered the transcriptome of fetal tissues. However, the mechanisms underlying transcriptomic changes are poorly understood. DNA methylation is an epigenetic mark regulating transcription and is largely influenced by dietary components of the one-carbon cycle that generate the methyl group donor, SAM. Therefore, in the present study, we tested whether different maternal diets during pregnancy would alter the DNA methylation and gene expression patterns in fetal tissues.

Results: Pregnant ewes were randomly divided into two groups which received either hay or corn diet from mid-gestation (day 67 ± 5) until day 131 ± 1 when fetuses were collected by necropsy. A total of 1516 fetal longissimus dorsi (LD) tissues were used for DNA methylation analysis and gene expression profiling. Whole genome DNA methylation using methyl-binding domain enrichment analysis revealed 60 differentially methylated regions (DMRs) between hay and corn fetuses with 39 DMRs more highly methylated in the hay fetuses vs. 21 DMRs more highly methylated in the corn fetuses. Three DMRs (LPAR3, PLIN5-PLIN4, and the differential methylation of a novel lincRNA) were validated using bisulfite sequencing. These DMRs were associated with differential gene expression. Additionally, significant DNA methylation differences were found at the single CpG level. Integrative methylome and transcriptome analysis revealed an association between gene expression and inter-/intragenic methylated regions. Furthermore, intragenic DMRs were found to be associated with expression of neighboring genes.

Conclusions: The findings of this study imply that maternal diet from mid- to late-gestation can shape the epigenome and the transcriptome of fetal tissues, and putatively affect phenotypes of the lambs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12864-018-4509-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5801776PMC
February 2018

MicroRNA Signaling in Embryo Development.

Biology (Basel) 2017 Sep 14;6(3). Epub 2017 Sep 14.

Department of Animal Sciences, University of Wisconsin-Madison, Madison, WI 53706, USA.

Expression of microRNAs (miRNAs) is essential for embryonic development and serves important roles in gametogenesis. miRNAs are secreted into the extracellular environment by the embryo during the preimplantation stage of development. Several cell types secrete miRNAs into biological fluids in the extracellular environment. These fluid-derived miRNAs have been shown to circulate the body. Stable transport is dependent on proper packaging of the miRNAs into extracellular vesicles (EVs), including exosomes. These vesicles, which also contain RNA, DNA and proteins, are on the forefront of research on cell-to-cell communication. Interestingly, EVs have been identified in many reproductive fluids, such as uterine fluid, where their miRNA content is proposed to serve as a mechanism of crosstalk between the mother and conceptus. Here, we review the role of miRNAs in molecular signaling and discuss their transport during early embryo development and implantation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/biology6030034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5617922PMC
September 2017

Sexual Dimorphism of miRNAs Secreted by Bovine -produced Embryos.

Front Genet 2017 4;8:39. Epub 2017 Apr 4.

Department of Animal Sciences, University of Wisconsin, MadisonWI, USA.

Sexual dimorphism of bovine blastocysts has previously been observed through differences in development, cell death, metabolism, telomere length, DNA methylation, and transcriptomics. However, dimorphism in the secretion of miRNAs to culture media has not yet been evaluated. The objectives of this study were to determine if sex-specific blastocyst miRNA secretion occurs and to further investigate the role these miRNAs may have in the interaction between a blastocyst and the maternal environment. embryo culture was performed and media from male and female blastocysts was collected into sex-specific pools. Profiling of 68 miRNAs revealed a total of eight miRNAs that were differentially expressed between female and male-conditioned media. Validation by qPCR confirmed higher expression of miR-22 ( < 0.05), miR-122 ( < 0.05), and miR-320a ( < 0.05) in female media for three additional biological replicates. To examine the potential roles of secreted miRNAs to the media in communication with the maternal environment, miR-22, miR-122, and miR-320a were each supplemented to four replicates of primary bovine endometrial epithelial cell culture. Uptake of miR-122 ( < 0.05) and miR-320a ( < 0.05) was detected, and a trend of uptake was detected for miR-22 ( > 0.05). Further, expression of the progesterone receptor transcript, a predicted target of all three miRNAs, was found to be upregulated in the cells following supplementation of miR-122 ( < 0.05) and miR-320a ( < 0.05), and a trend upregulation of the transcript was observed following miR-22 ( 0.05) supplementation. This work demonstrates that male and female conceptuses are able to differentially secrete miRNAs at the blastocyst stage and that these miRNAs have the ability to induce a transcriptomic response when applied to maternal cells. This knowledge builds on the known dimorphic differences in conceptuses at the blastocyst stage and demonstrates a role for blastocyst-secreted miRNAs in cell-cell communication.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fgene.2017.00039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5378762PMC
April 2017

Male fertility status is associated with DNA methylation signatures in sperm and transcriptomic profiles of bovine preimplantation embryos.

BMC Genomics 2017 04 5;18(1):280. Epub 2017 Apr 5.

Department of Animal Sciences, University of Wisconsin-Madison, Madison, WI, 53706, USA.

Background: Infertility in dairy cattle is a concern where reduced fertilization rates and high embryonic loss are contributing factors. Studies of the paternal contribution to reproductive performance are limited. However, recent discoveries have shown that, in addition to DNA, sperm delivers transcription factors and epigenetic components that are required for fertilization and proper embryonic development. Hence, characterization of the paternal contribution at the time of fertilization is warranted. We hypothesized that sire fertility is associated with differences in DNA methylation patterns in sperm and that the embryonic transcriptomic profiles are influenced by the fertility status of the bull. Embryos were generated in vitro by fertilization with either a high or low fertility Holstein bull. Blastocysts derived from each high and low fertility bulls were evaluated for morphology, development, and transcriptomic analysis using RNA-Sequencing. Additionally, DNA methylation signatures of sperm from high and low fertility sires were characterized by performing whole-genome DNA methylation binding domain sequencing.

Results: Embryo morphology and developmental capacity did not differ between embryos generated from either a high or low fertility bull. However, RNA-Sequencing revealed 98 genes to be differentially expressed at a false discovery rate < 1%. A total of 65 genes were upregulated in high fertility bull derived embryos, and 33 genes were upregulated in low fertility derived embryos. Expression of the genes CYCS, EEA1, SLC16A7, MEPCE, and TFB2M was validated in three new pairs of biological replicates of embryos. The role of the differentially expressed gene TFB2M in embryonic development was further assessed through expression knockdown at the zygotic stage, which resulted in decreased development to the blastocyst stage. Assessment of the epigenetic signature of spermatozoa between high and low fertility bulls revealed 76 differentially methylated regions.

Conclusions: Despite similar morphology and development to the blastocyst stage, preimplantation embryos derived from high and low fertility bulls displayed significant transcriptomic differences. The relationship between the paternal contribution and the embryonic transcriptome is unclear, although differences in methylated regions were identified which could influence the reprogramming of the early embryo. Further characterization of paternal factors delivered to the oocyte could lead to the identification of biomarkers for better selection of sires to improve reproductive efficiency.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12864-017-3673-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5382486PMC
April 2017

Dexrazoxane Diminishes Doxorubicin-Induced Acute Ovarian Damage and Preserves Ovarian Function and Fecundity in Mice.

PLoS One 2015 6;10(11):e0142588. Epub 2015 Nov 6.

Department of Obstetrics and Gynecology, University of Wisconsin, Madison, Wisconsin, United States of America.

Advances in cancer treatment utilizing multiple chemotherapies have dramatically increased cancer survivorship. Female cancer survivors treated with doxorubicin (DXR) chemotherapy often suffer from an acute impairment of ovarian function, which can persist as long-term, permanent ovarian insufficiency. Dexrazoxane (Dexra) pretreatment reduces DXR-induced insult in the heart, and protects in vitro cultured murine and non-human primate ovaries, demonstrating a drug-based shield to prevent DXR insult. The present study tested the ability of Dexra pretreatment to mitigate acute DXR chemotherapy ovarian toxicity in mice through the first 24 hours post-treatment, and improve subsequent long-term fertility throughout the reproductive lifespan. Adolescent CD-1 mice were treated with Dexra 1 hour prior to DXR treatment in a 1:1 mg or 10:1 mg Dexra:DXR ratio. During the acute injury period (2-24 hours post-injection), Dexra pretreatment at a 1:1 mg ratio decreased the extent of double strand DNA breaks, diminished γH2FAX activation, and reduced subsequent follicular cellular demise caused by DXR. In fertility and fecundity studies, dams pretreated with either Dexra:DXR dose ratio exhibited litter sizes larger than DXR-treated dams, and mice treated with a 1:1 mg Dexra:DXR ratio delivered pups with birth weights greater than DXR-treated females. While DXR significantly increased the "infertility index" (quantifying the percentage of dams failing to achieve pregnancy) through 6 gestations following treatment, Dexra pretreatment significantly reduced the infertility index following DXR treatment, improving fecundity. Low dose Dexra not only protected the ovaries, but also bestowed a considerable survival advantage following exposure to DXR chemotherapy. Mouse survivorship increased from 25% post-DXR treatment to over 80% with Dexra pretreatment. These data demonstrate that Dexra provides acute ovarian protection from DXR toxicity, improving reproductive health in a mouse model, suggesting this clinically available drug may provide ovarian protection for cancer patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0142588PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4636352PMC
June 2016

mRNA fragments in in vitro culture media are associated with bovine preimplantation embryonic development.

Front Genet 2015 24;6:273. Epub 2015 Aug 24.

Department of Animal Sciences, University of Wisconsin-Madison, Madison WI, USA.

In vitro production (IVP) systems have been used to bypass problems of fertilization and early embryonic development. However, embryos produced by IVP are commonly selected for implantation based on morphological assessment, which is not a strong indicator of establishment and maintenance of pregnancy. Thus, there is a need to identify additional indicators of embryonic developmental potential. Previous studies have identified microRNA expression in in vitro culture media to be indicative of embryo quality in both bovine and human embryos. Like microRNAs, mRNAs have been shown to be secreted from cells into the extracellular environment, but it is unknown whether or not these RNAs are secreted by embryos. Thus, the objective of the present study was to determine whether mRNAs are secreted into in vitro culture media and if their expression in the media is indicative of embryo quality. In vitro culture medium was generated and collected from both blastocyst and degenerate (those which fail to develop from the morula to blastocyst stage) embryos. Small-RNA sequencing revealed that many mRNA fragments were present in the culture media. A total of 17 mRNA fragments were differentially expressed between blastocyst and degenerate conditioned media. Differential expression was confirmed by quantitative real-time PCR for fragments of mRNA POSTN and VSNL-1, in four additional biological replicates of media. To better understand the mechanisms of mRNA secretion into the media, the expression of a predicted RNA binding protein of POSTN, PUM2, was knocked down using an antisense oligonucleotide gapmer. Supplementation of a PUM2 gapmer significantly reduced blastocyst development and decreased secretion of POSTN mRNA into the media. Overall, differential mRNA expression in the media was repeatable and sets the framework for future study of mRNA biomarkers in in vitro culture media to improve predictability of reproductive performance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fgene.2015.00273DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4547040PMC
September 2015

Exploring causal networks underlying fat deposition and muscularity in pigs through the integration of phenotypic, genotypic and transcriptomic data.

BMC Syst Biol 2015 Sep 16;9:58. Epub 2015 Sep 16.

Department of Animal Sciences, University of Wisconsin-Madison, Madison, WI, 53706, USA.

Background: Joint modeling and analysis of phenotypic, genotypic and transcriptomic data have the potential to uncover the genetic control of gene activity and phenotypic variation, as well as shed light on the manner and extent of connectedness among these variables. Current studies mainly report associations, i.e. undirected connections among variables without causal interpretation. Knowledge regarding causal relationships among genes and phenotypes can be used to predict the behavior of complex systems, as well as to optimize management practices and selection strategies. Here, we performed a multistep procedure for inferring causal networks underlying carcass fat deposition and muscularity in pigs using multi-omics data obtained from an F2 Duroc x Pietrain resource pig population.

Results: We initially explored marginal associations between genotypes and phenotypic and expression traits through whole-genome scans, and then, in genomic regions with multiple significant hits, we assessed gene-phenotype network reconstruction using causal structural learning algorithms. One genomic region on SSC6 showed significant associations with three relevant phenotypes, off-midline10th-rib backfat thickness, loin muscle weight, and average intramuscular fat percentage, and also with the expression of seven genes, including ZNF24, SSX2IP, and AKR7A2. The inferred network indicated that the genotype affects the three phenotypes mainly through the expression of several genes. Among the phenotypes, fat deposition traits negatively affected loin muscle weight.

Conclusions: Our findings shed light on the antagonist relationship between carcass fat deposition and lean meat content in pigs. In addition, the procedure described in this study has the potential to unravel gene-phenotype networks underlying complex phenotypes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12918-015-0207-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4574162PMC
September 2015

Characterization of microRNA in bovine in vitro culture media associated with embryo quality and development.

J Dairy Sci 2015 Sep 2;98(9):6552-63. Epub 2015 Jul 2.

Department of Animal Sciences, University of Wisconsin, Madison 53706. Electronic address:

Dairy cattle fertility has declined over time due to factors including reduced fertilization and early embryonic loss. To counter fertility problems and better study preimplantation embryonic development, in vitro production systems have been developed. These systems largely assess embryos based on their morphology, which is not a strong indicator of developmental potential. Currently, no biomarkers can be used to noninvasively survey an embryo's potential in terms of its development and ability to establish a pregnancy. Thus, the objective of this study was to characterize and identify microRNA (miRNA) in culture media of embryos of differing developmental competence for future development as noninvasive biomarkers of embryo quality. The MiRNA sequencing of media conditioned by blastocyst and degenerate (those that failed to develop from the morula to blastocyst stage) embryos, revealed 11 differentially expressed miRNA; all were higher in concentration in degenerate conditioned media. Differential expression of mature microRNA (miR)-24, miR-191, and miR-148a was further validated using quantitative real-time PCR. Functional analysis of miR-24 revealed that addition of a mimic miRNA to culture media of morulae embryos resulted in a 27.3% decrease in development to the blastocyst stage. Furthermore, expression of miR-24 was 44.29-fold higher in blastocysts cultured with a miR-24 mimic compared with control blastocysts. Interestingly, the expression of CDKN1b, a target gene of miR-24 was repressed in embryos grown in the presence of the miRNA mimic. Mimic supplementation experiments suggest that miRNA are taken up by the embryo and that extracellular miRNA affect embryonic development. Overall, identification of a rich extracellular milieu in conditioned media sets the framework for future studies to determine the long-term predictive ability of embryo-based miRNA biomarkers on pregnancy outcome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3168/jds.2015-9510DOI Listing
September 2015

Maternal nutrition induces gene expression changes in fetal muscle and adipose tissues in sheep.

BMC Genomics 2014 Nov 28;15:1034. Epub 2014 Nov 28.

Department of Animal Sciences, University of Wisconsin-Madison, 1675 Observatory Drive, Madison, WI 53706, USA.

Background: Maternal nutrition during different stages of pregnancy can induce significant changes in the structure, physiology, and metabolism of the offspring. These changes could have important implications on food animal production especially if these perturbations impact muscle and adipose tissue development. Here, we evaluated the impact of different maternal isoenergetic diets, alfalfa haylage (HY; fiber), corn (CN; starch), and dried corn distillers grains (DG; fiber plus protein plus fat), on the transcriptome of fetal muscle and adipose tissues in sheep.

Results: Prepartum diets were associated with notable gene expression changes in fetal tissues. In longissimus dorsi muscle, a total of 224 and 823 genes showed differential expression (FDR ≤0.05) in fetuses derived from DG vs. CN and HY vs. CN maternal diets, respectively. Several of these significant genes affected myogenesis and muscle differentiation. In subcutaneous and perirenal adipose tissues, 745 and 208 genes were differentially expressed (FDR ≤0.05), respectively, between CN and DG diets. Many of these genes are involved in adipogenesis, lipogenesis, and adipose tissue development. Pathway analysis revealed that several GO terms and KEGG pathways were enriched (FDR ≤0.05) with differentially expressed genes associated with tissue and organ development, chromatin biology, and different metabolic processes.

Conclusions: These findings provide evidence that maternal nutrition during pregnancy can alter the programming of fetal muscle and fat tissues in sheep. The ramifications of the observed gene expression changes, in terms of postnatal growth, body composition, and meat quality of the offspring, warrant future investigation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/1471-2164-15-1034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4301459PMC
November 2014

Expression of microRNAs in bovine and human pre-implantation embryo culture media.

Front Genet 2014 24;5:91. Epub 2014 Apr 24.

Department of Animal Sciences, University of Wisconsin-Madison Madison, WI, USA.

MicroRNAs (miRNA) are short non-coding RNAs which act to regulate expression of genes driving numerous cellular processes. These RNAs are secreted within exosomes from cells into the extracellular environment where they may act as signaling molecules. In addition, they are relatively stable and are specifically expressed in association to certain cancers making them strong candidates as biological markers. Moreover, miRNAs have been detected in body fluids including urine, milk, saliva, semen, and blood plasma. However, it is unknown whether they are secreted by embryonic cells into the culture media. Given that miRNAs are expressed throughout embryonic cellular divisions and embryonic genome activation, we hypothesized that they are secreted from the embryo into the extracellular environment and may play a role in the developmental competence of bovine embryos. To test this hypothesis, bovine embryos were cultured individually from day 5 to day 8 of development in an in vitro fertilization system and gene expression of 5 miRNAs was analyzed in both embryos and culture media. Differential miRNA gene expression was observed between embryos that developed to the blastocyst stage and those that failed to develop from the morula to blastocyst stage, deemed degenerate embryos. MiR-25, miR-302c, miR-196a2, and miR-181a expression was found to be higher in degenerate embryos compared to blastocyst embryos. Interestingly, these miRNAs were also found to be expressed in the culture media of both bovine and human pre-implantation embryos. Overall, our results show for the first time that miRNAs are secreted from pre-implantation embryos into culture media and that miRNA expression may correlate with developmental competence of the embryo. Expression of miRNAs in in vitro culture media could allow for the development of biological markers for selection of better quality embryos and for subsequent successful pregnancy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fgene.2014.00091DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4006060PMC
May 2014

Effect of maternal methionine supplementation on the transcriptome of bovine preimplantation embryos.

PLoS One 2013 21;8(8):e72302. Epub 2013 Aug 21.

Department of Animal Sciences, University of Wisconsin, Madison, Wisconsin, USA.

Maternal nutrition exclusively during the periconceptional period can induce remarkable effects on both oocyte maturation and early embryo development, which in turn can have lifelong consequences. The objective of this study was to evaluate the effect of maternal methionine supplementation on the transcriptome of bovine preimplantation embryos. Holstein cows were randomly assigned to one of two treatments differing in level of dietary methionine (1.89 Met vs. 2.43 Met % of metabolizable protein) from calving until embryo flushing. High quality preimplantation embryos from individual cows were pooled and then analyzed by RNA sequencing. Remarkably, a subtle difference in methionine supplementation in maternal diet was sufficient to cause significant changes in the transcriptome of the embryos. A total of 276 genes out of 10,662 showed differential expression between treatments (FDR <0.10). Interestingly, several of the most significant genes are related to embryonic development (e.g., VIM, IFI6, BCL2A1, and TBX15) and immune response (e.g., NKG7, TYROBP, SLAMF7, LCP1, and BLA-DQB). Likewise, gene set enrichment analysis revealed that several Gene Ontology terms, InterPro entries, and KEGG pathways were enriched (FDR <0.05) with differentially expressed genes involved in embryo development and immune system. The expression of most genes was decreased by maternal methionine supplementation, consistent with reduced transcription of genes with increased methylation of specific genes by increased methionine. Overall, our findings provide evidence that supplementing methionine to dams prior to conception and during the preimplantation period can modulate gene expression in bovine blastocysts. The ramifications of the observed gene expression changes for subsequent development of the pregnancy and physiology of the offspring warrant further investigation in future studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0072302PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3749122PMC
June 2014

Knockdown of CDKN1C (p57(kip2)) and PHLDA2 results in developmental changes in bovine pre-implantation embryos.

PLoS One 2013 22;8(7):e69490. Epub 2013 Jul 22.

Department of Dairy Science, University of Wisconsin-Madison, Madison, Wisconsin, USA.

Imprinted genes have been implicated in early embryonic, placental, and neonatal development and alterations in expression levels of these genes can lead to growth abnormalities and embryonic lethality. However, little is known about the functions of bovine imprinted genes during the pre-implantation period. Therefore, the objective of this study was to assess the influence of altered expression of imprinted genes on developmental progress of embryos using small interfering RNA (siRNA). Expression levels of 18 imprinted genes (MAGEL2, UBE3A, IGF2R, NAP1L5, TSSC4, PEG3, NDN, CDKN1C, PHLDA2, MKRN3, USP29, NNAT, PEG10, RTL1, IGF2, H19, MIM1, and XIST) were compared between embryos reaching the blastocyst stage and growth-arrested embryos (degenerates) using quantitative real-time PCR (qRT-PCR). Ten genes were found to be differentially expressed between blastocysts and degenerates. The CDKN1C gene showed the highest upregulation in blastocysts whereas PHLDA2 was highly expressed in degenerates. To assess whether the observed differential gene expression was causative or resultant of embryo degeneration, these genes were selected for functional analysis using siRNA. Injection of siRNA specific to PHLDA2 into one-cell zygotes resulted in a substantial increase in blastocyst development, whereas injection of CDKN1C-specific siRNA resulted in a 45% reduction (P = 0.0006) in blastocyst development. RNA-Seq analysis of CDKN1C-siRNA-injected vs. non-injected embryos revealed 51 differentially expressed genes with functions in apoptosis, lipid metabolism, differentiation, and cell cycle regulation. Gene ontology analysis revealed nine pathways related to cell signaling, metabolism, and nucleic acid processing. Overall, our results show that proper expression levels of the imprinted genes CDKN1C and PHLDA2 are critical for embryo development, which suggests that these genes can be used as markers for normal blastocyst formation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0069490PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3718760PMC
February 2014

Maternal Diet during Pregnancy Induces Gene Expression and DNA Methylation Changes in Fetal Tissues in Sheep.

Front Genet 2013 5;4:49. Epub 2013 Apr 5.

College of Animal Science and Technology, Northwest Agriculture and Forestry University Yangling, China ; Department of Animal Sciences, University of Wisconsin-Madison Madison, WI, USA.

Studies in rats and mice have established that maternal nutrition induces epigenetic modifications, sometimes permanently, that alter gene expression in the fetus, which in turn leads to phenotypic changes. However, limited data is available on the influence of maternal diet on epigenetic modifications and gene expression in sheep. Therefore, the objectives of this study were to investigate the impact of different maternal dietary energy sources on the expression of imprinted genes in fetuses in sheep. Ewes were naturally bred to a single sire and from days 67 ± 3 of gestation until necropsy (days 130 ± 1), they were fed one of three diets of alfalfa haylage (HY; fiber), corn (CN; starch), or dried corn distiller's grains (DG; fiber plus protein plus fat). A total of 26 fetuses were removed from the dams and longissimus dorsi, semitendinosus, perirenal adipose depot, and subcutaneous adipose depot tissues were collected for expression and DNA methylation analyses. Expression analysis of nine imprinted genes and three DNA methyltransferase (DNMTs) genes showed significant effects of the different maternal diets on the expression of these genes. The methylation levels of CpG islands of both IGF2R and H19 were higher in HY and DG than CN fetuses in both males and females. This result is consistent with the low amino acid content of the CN diet, a source of methyl group donors, compared to HY and DG diets. Thus, results of this study provide evidence of association between maternal nutrition during pregnancy and transcriptomic and epigenomic alterations of imprinted genes and DNMTs in the fetal tissues.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fgene.2013.00049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3617393PMC
April 2013

Inferring quantitative trait pathways associated with bull fertility from a genome-wide association study.

Front Genet 2012 11;3:307. Epub 2013 Jan 11.

Department of Animal Sciences, University of Wisconsin Madison, WI, USA.

Whole-genome association studies typically focus on genetic markers with the strongest evidence of association. However, single markers often explain only a small component of the genetic variance and hence offer a limited understanding of the trait under study. As such, the objective of this study was to perform a pathway-based association analysis in Holstein dairy cattle in order to identify relevant pathways involved in bull fertility. The results of a single-marker association analysis, using 1,755 bulls with sire conception rate data and genotypes for 38,650 single nucleotide polymorphisms (SNPs), were used in this study. A total of 16,819 annotated genes, including 2,767 significantly associated with bull fertility, were used to interrogate a total of 662 Gene Ontology (GO) terms and 248 InterPro (IP) entries using a test of proportions based on the cumulative hypergeometric distribution. After multiple-testing correction, 20 GO categories and one IP entry showed significant overrepresentation of genes statistically associated with bull fertility. Several of these functional categories such as small GTPases mediated signal transduction, neurogenesis, calcium ion binding, and cytoskeleton are known to be involved in biological processes closely related to male fertility. These results could provide insight into the genetic architecture of this complex trait in dairy cattle. In addition, this study shows that quantitative trait pathways inferred from single-marker analyses could enhance our interpretations of the results of genome-wide association studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fgene.2012.00307DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3542705PMC
January 2013

Bovine genomics by james e. Womack.

Authors:
Hasan Khatib

Front Genet 2012 27;3:275. Epub 2012 Nov 27.

Department of Animal Sciences, University of Wisconsin-Madison Madison, WI, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fgene.2012.00275DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3536026PMC
January 2013

Genes of the transforming growth factor-beta signalling pathway are associated with pre-implantation embryonic development in cattle.

J Dairy Res 2012 Aug 12;79(3):310-7. Epub 2012 Jun 12.

College of Animal Science and Technology, China Agricultural University, Beijing 100193, China.

One of the main factors affecting cattle fertility is pre-implantation development of the bovine embryo, which is a complex process regulated by various signal-transduction pathways. The transforming growth factor-β (TGF-β) signalling system, which is responsible for many biological processes including cell proliferation, differentiation and apoptosis, also is involved in embryo development. We hypothesized that altered expression of TGF-β genes in pre-implantation bovine embryos is associated with morphological abnormalities of these embryos. To test this hypothesis, we produced embryos in vitro and classified them at the blastocyst stage as either normally developed blastocysts or degenerates (growth-arrested embryos). The expression patterns of 25 genes from the TGF-β pathway were assessed using quantitative real time PCR. Ten genes showed differential expression between the two embryo groups, four genes displayed similar expressional profiles, and 11 genes had no detectable expression. An altered expression profile was statistically significant for 10 of the 14 expressed genes, and all were up-regulated in degenerate embryos vs. blastocysts. Furthermore, genomic association analysis of the cows from which embryos were produced revealed a significant association of ID3 and BMP4 polymorphisms--two of the most significant differentially expressed genes--with fertilization rate and blastocyst rate, respectively. Taken together, we conclude that TGF-β pathway genes, especially BMP4 and ID3 play a vital function in the regulation of pre-implantation embryo development at both embryo and maternal levels. Hence, these genes may be suitable as genetic markers for embryo development and fertility in cattle.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1017/S0022029912000210DOI Listing
August 2012

Genome-wide identification and initial characterization of bovine long non-coding RNAs from EST data.

Anim Genet 2012 Dec 8;43(6):674-82. Epub 2012 Feb 8.

Department of Dairy Science, University of Wisconsin-Madison, Madison, WI 53706, USA.

It has become increasingly clear that the mammalian genomes produce many long non-coding RNAs (lncRNAs). Accumulating evidence suggests important functions for lncRNAs in a variety of biological processes. However, little is known about lncRNA identity and characteristics in cattle. Using public bovine-specific expressed sequence tags sequences, we reconstructed transcript assemblies, from which reference sequences were obtained for RNAs. Intergenic regions with evidence of transcription were screened for putative lncRNAs using the combination of a gene-finding program and a support vector machine-based tool for the calculation of protein-coding potential. A total of 449 putative lncRNAs located in 405 intergenic regions were identified. Characterization of these putative bovine lncRNAs suggests that they are generally expressed in a tissue-specific manner, their GC contents are higher than randomly selected intergenic sequences but are lower than protein-coding genes, and they are moderately conserved among mammals. This is the first genome-wide catalogue of putative intergenic lncRNAs in cattle and provides important targets for functional studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1365-2052.2012.02325.xDOI Listing
December 2012

RNA-Seq analysis uncovers transcriptomic variations between morphologically similar in vivo- and in vitro-derived bovine blastocysts.

BMC Genomics 2012 Mar 28;13:118. Epub 2012 Mar 28.

Department of Dairy Science, University of Wisconsin, Madison, WI 53706, USA.

Background: A valuable tool for both research and industry, in vitro fertilization (IVF) has applications range from gamete selection and preservation of traits to cloning. Although IVF has achieved worldwide use, with approximately 339,685 bovine embryos transferred in 2010 alone, there are still continuing difficulties with efficiency. It is rare to have more than 40% of fertilized in vitro cattle oocytes reach blastocyst stage by day 8 of culture, and pregnancy rates are reported as less than 45% for in vitro produced embryos. To investigate potential influences in-vitro fertilization (IVF) has on embryonic development, this study compares in vivo- and in vitro-derived bovine blastocysts at a similar stage and quality grade (expanded, excellent quality) to determine the degree of transcriptomic variation beyond morphology using RNA-Seq.

Results: A total of 26,906,451 and 38,184,547 fragments were sequenced for in vitro and in vivo embryo pools, respectively. We detected expression for a total of 17,634 genes, with 793 genes showing differential expression between the two embryo populations with false discovery rate (FDR) < 0.05. There were also 395 novel transcribed units found, of which 45 were differentially expressed (FDR < 0.05). In addition, 4,800 genes showed evidence of alternative splicing, with 873 genes displaying differential alternative splicing between the two pools (FDR < 0.05). Using GO enrichment analysis, multiple biological pathways were found to be significantly enriched for differentially expressed genes (FDR < 0.01), including cholesterol and sterol synthesis, system development, and cell differentiation.

Conclusions: Thus, our results support that IVF may influence at the transcriptomic level and that morphology is limited in full characterization of bovine preimplantation embryos.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/1471-2164-13-118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3368723PMC
March 2012

Characterization and comparison of the leukocyte transcriptomes of three cattle breeds.

PLoS One 2012 23;7(1):e30244. Epub 2012 Jan 23.

Department of Dairy Science, University of Wisconsin, Madison, Wisconsin, United States of America.

In this study, mRNA-Seq was used to characterize and compare the leukocyte transcriptomes from two taurine breeds (Holstein and Jersey), and one indicine breed (Cholistani). At the genomic level, we identified breed-specific base changes in protein coding regions. Among 7,793,425 coding bases, only 165 differed between Holstein and Jersey, and 3,383 (0.04%) differed between Holstein and Cholistani, 817 (25%) of which resulted in amino acid changes in 627 genes. At the transcriptional level, we assembled transcripts and estimated their abundances including those from more than 3,000 unannotated intergeneic regions. Differential gene expression analysis showed a high similarity between Holstein and Jersey, and a much greater difference between the taurine breeds and the indicine breed. We identified gene ontology pathways that were systematically altered, including the electron transport chain and immune response pathways that may contribute to different levels of heat tolerance and disease resistance in taurine and indicine breeds. At the post-transcriptional level, sequencing mRNA allowed us to identify a number of genes undergoing differential alternative splicing among different breeds. This study provided a high-resolution survey of the variation between bovine transcriptomes at different levels and may provide important biological insights into the phenotypic differentiation among cattle breeds.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0030244PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3264571PMC
June 2012

Association of milk protein genes with fertilization rate and early embryonic development in Holstein dairy cattle.

J Dairy Res 2012 Feb 13;79(1):47-52. Epub 2011 Oct 13.

Department of Animal Sciences, University of Wisconsin-Madison, Madison, WI, USA.

Concomitant with intensive selection for increased milk yield, reproductive performance of dairy cows has declined in the last decades, in part due to an unfavourable genetic relationship between these traits. Given that the six main milk protein genes (i.e. whey proteins and caseins) are directly involved in milk production and hence have been a target of the strong selection aimed at improving milk yield in dairy cattle, we hypothesized that these genes could show selection footprints associated with fertility traits. In this study, we used an in-vitro fertilization (IVF) system to test genetic association between 66 single nucleotide polymorphisms (SNPs) in the four caseins (αS1-casein, αS2-casein, β-casein and κ-casein) and the two whey protein genes (α-lactalbumin and β-lactoglobulin) with fertilization rate and early embryonic development in the Holstein breed. A total of 6893 in-vitro fertilizations were performed and a total of 4661 IVF embryos were produced using oocytes from 399 ovaries and semen samples from 12 bulls. Associations between SNPs and fertility traits were analysed using a mixed linear model with genotype as fixed effect and ovary and bull as random effects. A multiple testing correction approach was used to account for the correlation between SNPs due to linkage disequilibrium. After correction, polymorphisms in the LALBA and LGB genes showed significant associations with fertilization success and blastocyst rate. No significant associations were detected between SNPs located in the casein region and IVF fertility traits. Although the molecular mechanisms underlying the association between whey protein genes and fertility have not yet been characterized, this study provides the first evidence of association between these genes and fertility traits. Furthermore, these results could shed light on the antagonistic relationship that exists between milk yield and fertility in dairy cattle.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1017/S0022029911000744DOI Listing
February 2012

Comparison of transcriptomic landscapes of bovine embryos using RNA-Seq.

BMC Genomics 2010 Dec 17;11:711. Epub 2010 Dec 17.

Department of Dairy Science, University of Wisconsin, Madison, WI 53706, USA.

Background: Advances in sequencing technologies have opened a new era of high throughput investigations. Although RNA-seq has been demonstrated in many organisms, no study has provided a comprehensive investigation of the bovine transcriptome using RNA-seq.

Results: In this study, we provide a deep survey of the bovine embryonic transcriptomes, the first application of RNA-seq in cattle. Embryos cultured in vitro were used as models to study early embryonic development in cattle. RNA amplified from limited amounts of starting total RNA were sequenced and mapped to the reference genome to obtain digital gene expression at single base resolution. In particular, gene expression estimates from more than 1.6 million unannotated bases in 1785 novel transcribed units were obtained. We compared the transcriptomes of embryos showing distinct developmental statuses and found genes that showed differential overall expression as well as alternative splicing.

Conclusion: Our study demonstrates the power of RNA-seq and provides further understanding of bovine preimplantation embryonic development at a fine scale.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/1471-2164-11-711DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3019235PMC
December 2010

Upregulation of imprinted genes in mice: an insight into the intensity of gene expression and the evolution of genomic imprinting.

Epigenetics 2010 Feb 1;5(2):149-58. Epub 2010 Mar 1.

Department of Dairy Science, University of Wisconsin, Madison, WI, USA.

Imprinted genes are expressed monoallelically because one of the two copies is silenced epigentically in a parent-of-origin pattern. This pattern of expression is controlled by differential marking of parental alleles by DNA methylation and chromatin modifications, including both suppressive and permissive histone acetylation and methylation. Suppressive histone modifications mark silenced alleles of imprinted genes, while permissive histone modifications mark the active alleles, suggesting the possibility that imprinted genes would show upregulation in gene expression. However, it is currently unknown whether imprinted genes show such upregulation. To address this question in mice, we estimated the intensity of expression of 59 genes relative to the rest of the genome by analyzing microarray data. Expression levels of 24 genes were validated using quantitative real-time PCR (qPCR). Expression of imprinted genes was found to be upreguled in various adult and embryonic mouse tissues. Consistent with their functions in growth and development, imprinted genes were found to be highly expressed in extraembryonic tissues and progressively upregulated during early embryonic development. In conclusion, upregulation of imprinted genes found in this study is similar to the dosage compensation (twofold upregulation) recently reported for X-linked genes. It has been proposed that the twofold upregulation of X-linked genes has been coupled with low transcriptional variation (noise) which could lead to deleterious effects on the organism. Results of this study suggest a general need for imprinted genes in the mouse to be upregulated to certain levels in order to avoid deleterious effects of variation in gene expression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3020655PMC
http://dx.doi.org/10.4161/epi.5.2.11081DOI Listing
February 2010

Transcriptomic profiling of bovine IVF embryos revealed candidate genes and pathways involved in early embryonic development.

BMC Genomics 2010 Jan 11;11:23. Epub 2010 Jan 11.

Department of Dairy Science, University of Wisconsin-Madison, Madison, WI 53706, USA.

Background: Early embryonic loss is a large contributor to infertility in cattle. Although genetic factors are known to affect early embryonic development, the discovery of such factors has been a serious challenge. The objective of this study was to identify genes differentially expressed between blastocysts and degenerative embryos at early stages of development.

Results: Using microarrays, genome-wide RNA expression was profiled and compared for in vitro fertilization (IVF) - derived blastocysts and embryos undergoing degenerative development up to the same time point. Surprisingly similar transcriptomic profiles were found in degenerative embryos and blastocysts. Nonetheless, we identified 67 transcripts that significantly differed between these two groups of embryos at a 15% false discovery rate, including 33 transcripts showing at least a two-fold difference. Several signaling and metabolic pathways were found to be associated with the developmental status of embryos, among which were previously known important steroid biosynthesis and cell communication pathways in early embryonic development.

Conclusions: This study presents the first direct and comprehensive comparison of transcriptomes between IVF blastocysts and degenerative embryos, providing important information for potential genes and pathways associated with early embryonic development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/1471-2164-11-23DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2824717PMC
January 2010

The genome sequence of taurine cattle: a window to ruminant biology and evolution.

Science 2009 Apr;324(5926):522-8

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1126/science.1169588DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2943200PMC
April 2009