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Journal of Dairy Science Jan 2021Development of ketosis in high-producing dairy cows contributes to several animal health issues and highlights the need for a better understanding of the genetic basis... (Meta-Analysis)
Meta-Analysis
Development of ketosis in high-producing dairy cows contributes to several animal health issues and highlights the need for a better understanding of the genetic basis of metabolic diseases. To evaluate the pattern of differential gene expression in the liver of cows under negative energy balance (NEB), and under subclinical and clinical ketosis, a meta-analysis of gene expression and genome-wide association studies results was performed. An initial systematic review identified 118 articles based on the key words "cow," "liver," "negative energy balance," "ketosis," "expression," "qPCR," "microarray," "proteomic," "RNA-Seq," and "GWAS." After further screening for only peer-reviewed and pertinent articles for gene expression during NEB and clinical and subclinical ketosis (considering plasma levels of β-hydroxybutyrate), 20 articles were included in the analysis. From the systematic review, 430 significant SNPs identified by genome-wide association studies (GWAS) were assigned to genes reported in gene expression studies by considering chromosome and base pair positions in the ARS-UCD 1.2 bovine assembly. Venn diagrams were created to integrate the data obtained in the systematic review, and Gene Ontology enrichment analysis was carried out using official gene names. A QTL enrichment analysis was also performed to identify potential positional candidate loci. Twenty-four significant SNPs were located within the coordinates of differentially expressed genes located on chromosomes 2, 3, 6, 9, 11, 14, 27, and 29. Three significant metabolic pathways were associated with NEB and subclinical and clinical ketosis. In addition, 2 important genes, PPARA (peroxisome proliferator activated receptor alpha) and ACACA (acetyl-coenzyme A carboxylase α), were identified, which were differentially expressed in the 3 metabolic conditions. The PPARA gene is involved in the regulation of lipid metabolism and fatty liver disease and the ACACA gene encodes an enzyme that catalyzes the carboxylation of acetyl-coenzyme A to malonyl-coenzyme A, which is a rate-limiting step in fatty acid synthesis. Gene network analysis revealed co-expression interactions among 34 genes associated with functions involving fatty acid transport and fatty acid metabolism. For the annotated QTL, 9 QTL were identified for ketosis. The genes FN1 (fibronectin 1) and PTK2 (protein tyrosine kinase 2), which are mainly involved in cell adhesion and formation of extracellular matrix constituents, were enriched for QTL previously associated with the trait "ketosis" on chromosome 2 and for the trait "milk iron content" on chromosome 14, respectively. This integration of gene expression and GWAS data provides an additional understanding of the genetic background of NEB and subclinical and clinical ketosis in dairy cattle. Thus, it is a useful approach to identify biological mechanisms underlying these metabolic conditions in dairy cattle.
Topics: Animals; Cattle; Cattle Diseases; Energy Metabolism; Female; Gene Expression
PubMed: 33189279
DOI: 10.3168/jds.2020-18883 -
Clinical Colorectal Cancer Oct 2009The use of adjuvant therapy in stage II colorectal cancer (CRC) remains controversial. There is a need to identify more effective predictors than the traditional staging... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
The use of adjuvant therapy in stage II colorectal cancer (CRC) remains controversial. There is a need to identify more effective predictors than the traditional staging system to aid therapeutic decision-making. We performed a systematic review and meta-analysis of gene expression profiles (GEPs) to assess their utility for risk stratification and prediction of poor outcomes in stage II CRC.
PATIENTS AND METHODS
We performed a comprehensive literature search through December 2007. Studies were included if they reported GEP-based assays in patients with stage II CRC, and either subsequent cancer recurrence or death within 3 years. The prognostic likelihood ratio (LR) and odds ratio (OR) were calculated with 95% confidence intervals and pooled using the fixed-effects method. The weighted average sensitivity, specificity, and accuracy were also reported.
RESULTS
Eight cohorts involving 271 patients contributed to the analysis. The average accuracy, sensitivity, and specificity were 81.9%, 76.2%, and 84.5%, respectively, with a prognostic LR of 4.7 (95% CI, 3.2-6.8) and a prognostic OR of 15.1 (95% CI, 7.9-28.6). No evidence for significant interstudy heterogeneity was noted in either analysis. Subgroup analysis found no difference in results for the prediction of cancer recurrence or death.
CONCLUSION
This analysis demonstrates the promising potential of using GEP assays as predictors of poor outcomes in stage II CRC, such as cancer recurrence or death. To maximize their utility and availability, further studies will be needed to identify and validate specific gene signatures for poor prognosis in stage II CRC.
Topics: Antineoplastic Agents; Biomarkers, Tumor; Colorectal Neoplasms; DNA, Neoplasm; Gene Expression Profiling; Humans; Neoplasm Staging; Oligonucleotide Array Sequence Analysis; Treatment Outcome
PubMed: 19822511
DOI: 10.3816/CCC.2009.n.035 -
Journal of Pediatric Genetics Sep 2020Oculoauriculovertebral spectrum (OAVS) is a rare class of heterogenous congenital craniofacial malformation conditions of unknown etiology. Although classic OAVS has... (Review)
Review
Microarray-Based Comparative Genomic Hybridization, Multiplex Ligation-Dependent Probe Amplification, and High-Resolution Karyotype for Differential Diagnosis Oculoauriculovertebral Spectrum: A Systematic Review.
Oculoauriculovertebral spectrum (OAVS) is a rare class of heterogenous congenital craniofacial malformation conditions of unknown etiology. Although classic OAVS has been described as hemifacial microsomia with facial asymmetry and microtia, there is no consensus regarding clinical criteria for diagnosis or genetic cause. This systematic review aims to assess the applicability of high-resolution (HR) karyotype, fluorescence in situ hybridization, multiplex ligation-dependent probe amplification (MLPA), and microarray-based comparative genomic hybridization (array-CGH) for differential diagnosis of OAVS. A search was performed in PubMed and Web of Science using all entry terms to the following descriptors: Goldenhar's syndrome, cytogenetic analysis, hybridization in situ, fluorescent, comparative genomic hybridization, multiplex polymerase chain reaction, whole genome sequencing, and karyotype analysis methods. After screening, 25 articles met eligibility. Of the included studies, 59 individuals had a genetic alteration identified. Array-CGH, MLPA, and HR karyotype appear to be viable approaches for molecular diagnosis in OAVS. Heterogeneity is a hallmark of OAVS. Establishing an enhanced framework for diagnosis would inform clinical decision making, and better resource utilization could improve health care facility efficiency and economy.
PubMed: 32714614
DOI: 10.1055/s-0040-1712118 -
American Journal of Medical Genetics.... Jun 2018Holoprosencephaly (HPE) is a structural brain anomaly characterized by failure of the forebrain to separate during early embryogenesis. Both genetic and environmental... (Meta-Analysis)
Meta-Analysis
Holoprosencephaly (HPE) is a structural brain anomaly characterized by failure of the forebrain to separate during early embryogenesis. Both genetic and environmental etiologies of HPE have been discovered over the last three decades. Traditionally, the genetic workup for HPE has been a karyotype, chromosomal microarray, and/or Sanger sequencing of select genes. The recent increased availability of next-generation sequencing has changed the molecular diagnostic landscape for HPE, associating new genes with this disorder such as FGFR1. We conducted a systematic review of the medical literature for the molecular testing of HPE for studies published in the last 20 years. We also queried known commercial diagnostic laboratories and used information on their websites to construct a list of available commercial testing. Our group released its first recommendations in 2010 and this update incorporates the technology shifts and gene discoveries over the last decade. These recommendations provide a guide for genetic diagnosis of HPE, which is paramount for patients and their families for prognosis, treatment, and genetic counseling.
Topics: Algorithms; Alleles; Genes, Recessive; Genetic Counseling; Genetic Markers; Genetic Testing; High-Throughput Nucleotide Sequencing; Holoprosencephaly; Humans; Karyotyping
PubMed: 29771000
DOI: 10.1002/ajmg.c.31617 -
Cancer Cell International 2018Many studies have investigated the prognostic role of biomarkers in colorectal liver metastases (CRLM). However, no biomarker has been established in routine clinical... (Review)
Review
BACKGROUND
Many studies have investigated the prognostic role of biomarkers in colorectal liver metastases (CRLM). However, no biomarker has been established in routine clinical practice. The aim of this study was to scrutinize the current literature for biomarkers evaluated by immunohistochemistry as prognostic markers in patients with resected CRLM.
METHODS
A systematic review was performed according to the PRISMA guidelines. Articles were identified in the PubMed database with selected search terms and by cross-references search. The REMARK quality criteria were applied. Markers were included if they reported the prognostic impact of immunohistochemical markers in a multivariable setting in relation to overall survival (OS). A meta-analysis was conducted when more than one original article provided survival data of a marker.
RESULTS
In total, 26 biomarkers were identified as independent significant markers for OS in resected CRLM. These biomarkers were found to be involved in multiple oncogenic signalling pathways that control cell growth, apoptosis, angiogenesis and evasion of immune detection. Among these biomarker candidates were Ki-67, EGFR, p53, hTERT, CD34, TSP-1, KISS1, Aurora kinase A and CDX2. CD34 and TSP-1 were reported as significantly associated with survival by more than one study and where therefore pooled in a meta-analysis.
CONCLUSION
A number of independent prognostic biomarkers for resected CRLM were identified. However, most markers were evaluated in a retrospective setting with small patient cohorts, without external validation. Large, prospective, multicentre studies with standardised methods are needed before biomarkers can translated into the clinic.
PubMed: 30602942
DOI: 10.1186/s12935-018-0715-8 -
Aging Dec 2020Dysregulation of α(1,6)-fucosyltransferase (FUT8) plays significant roles in development of a variety of malignant tumor types. We collected as many relevant articles... (Meta-Analysis)
Meta-Analysis
Dysregulation of α(1,6)-fucosyltransferase (FUT8) plays significant roles in development of a variety of malignant tumor types. We collected as many relevant articles and microarray datasets as possible to assess the prognostic value of FUT8 expression in malignant tumors. For this purpose, we systematically searched PubMed, Embase, Web of Science, Springer, Chinese National Knowledge Infrastructure (CNKI), and Wan Fang, and eventually identified 7 articles and 35 microarray datasets (involving 6124 patients and 10 tumor types) for inclusion in meta-analysis. In each tumor type, FUT8 expression showed significant (p< 0.05) correlation with one or more clinicopathological parameters; these included patient gender, molecular subgroup, histological grade, TNM stage, estrogen receptor, progesterone receptor, and recurrence status. In regard to survival prognosis, FUT8 expression level was associated with overall survival in non-small cell lung cancer (NSCLC), breast cancer, diffuse large B cell lymphoma, gastric cancer, and glioma. FUT8 expression was also correlated with disease-free survival in NSCLC, breast cancer, and colorectal cancer, and with relapse-free survival in pancreatic ductal adenocarcinoma. For most tumor types, survival prognosis of patients with high FUT8 expression was related primarily to clinical features such as gender, tumor stage, age, and pathological category. Our systematic review and meta-analysis confirmed the association of FUT8 with clinicopathological features and patient survival rates for numerous malignant tumor types. Verification of prognostic value of FUT8 in these tumor types will require a large-scale study using standardized methods of detection and analysis.
Topics: Biomarkers, Tumor; Fucosyltransferases; Gene Expression Regulation, Neoplastic; Humans; Neoplasms
PubMed: 33323540
DOI: 10.18632/aging.202239 -
American Journal of Medical Genetics.... Sep 2016Over the last decade, several advances in ultrasound techniques, increasing availability of whole genome microarray testing, and overall expansion of our knowledge about... (Meta-Analysis)
Meta-Analysis Review
Over the last decade, several advances in ultrasound techniques, increasing availability of whole genome microarray testing, and overall expansion of our knowledge about the human genome have drastically enhanced our ability to detect chromosomal abnormalities prenatally. Despite that, genotype-phenotype correlation is difficult to establish for many chromosomal aberrations, particularly for those that are rare, as it requires thorough analysis of a significant number of cases. This in turn increases the burden of the obstetric provider to appropriately counsel a patient regarding prognosis and pregnancy options in these complicated situations. Our experience in prenatal diagnosis and management of a fetus with multiple anomalies and partial trisomy for the 14q11-q24.2 prompted a comprehensive analysis of the relevant literature. Although complete non-mosaic trisomy 14 is associated with first trimester miscarriages, partial trisomy 14q is a rare condition with undefined genotype-phenotype correlation, preventing accurate prenatal counseling, and informed decision making. We performed a systematic literature review, that aimed to summarize prenatal and postnatal findings of individual case reports on 51 patients with partial trisomy 14q in order to elucidate genotype-phenotype correlation, and to supply healthcare professionals with recommendation on essential fetal and parental testing for accurate diagnosis, pregnancy outcomes, and proper family counseling. Comparison of the clinical findings among the patients with partial 14q trisomy suggest that the resulting phenotype is likely to be influenced by the extent of the 14q trisomy segment, associated chromosomal imbalances, parental origin of the rearrangement, and dosage of the genes within the imprinted 14q32 cluster. © 2016 Wiley Periodicals, Inc.
Topics: Chromosomes, Human, Pair 14; Comparative Genomic Hybridization; Disease Management; Female; Genetic Association Studies; Genetic Counseling; Genetic Testing; Humans; In Situ Hybridization, Fluorescence; Oligonucleotide Array Sequence Analysis; Polymorphism, Single Nucleotide; Pregnancy; Pregnancy Outcome; Trisomy; Ultrasonography, Prenatal
PubMed: 27286879
DOI: 10.1002/ajmg.a.37793 -
Genetics in Medicine : Official Journal... May 2011Autism is one of the most heritable complex disorders, but the genetic etiology of autism spectrum disorders is unexplained in ∼ 90% of cases. Highly penetrant... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Autism is one of the most heritable complex disorders, but the genetic etiology of autism spectrum disorders is unexplained in ∼ 90% of cases. Highly penetrant microdeletions and microduplications of 16p11.2 contribute to the pathogenesis of autism spectrum disorder, but the extent to which these variants account for the total burden of idiopathic autism spectrum disorders has not been systematically investigated.
METHODS
A systematic literature review and meta-analysis were performed to determine the prevalence of these variants among individuals diagnosed with autism spectrum disorders. A planned subgroup analysis was conducted to assess prevalence differences between sporadic and familial autism spectrum disorder cases.
RESULTS
In the combined analysis of 3613 idiopathic autism spectrum disorder cases from seven studies, the meta-analytic prevalence of these microdeletions and microduplications was 0.76% (95% CI, 0.51-1.12%). When stratified by copy number variant-type, the prevalence of microdeletions was 0.50% (95% CI, 0.31-0.82%) and the prevalence of microduplications was 0.28% (95% CI, 0.14-0.56%). Sporadic autism spectrum disorder cases showed only a slightly higher prevalence than familial cases.
CONCLUSION
The number needed to test to identify one such variant is 132 patients (95% CI, 89-198). Such information, especially as it pertains to diagnostic yield in genetic testing, should prove useful to clinicians considering chromosomal microarray analysis in subjects with autism spectrum disorders.
Topics: Child; Child Development Disorders, Pervasive; Chromosome Deletion; Chromosome Duplication; Chromosomes, Human, Pair 16; DNA Copy Number Variations; Gene Dosage; Humans; Incidence; Publication Bias
PubMed: 21289514
DOI: 10.1097/GIM.0b013e3182076c0c -
Dose-response : a Publication of... 2019Radiation therapy induces acute and chronic radiological toxicity, in particular hematological toxicity (HT). This study aimed to explore the mechanistic clue and... (Review)
Review
Analysis of mRNA Expression Patterns in Peripheral Blood Cells of 3 Patients With Cancer After the First Fraction of 2 Gy Irradiation: An Integrated Case Report and Systematic Review.
BACKGROUND
Radiation therapy induces acute and chronic radiological toxicity, in particular hematological toxicity (HT). This study aimed to explore the mechanistic clue and potential predictors at the messenger RNA (mRNA) level.
MATERIALS AND METHODS
Peripheral blood was collected from 3 patients with cervical cancer (CC), nasopharynx cancer (NC), and tongue cancer (TC) after the first 2 Gy fraction of radiotherapy (RT). High-throughput sequencing was used to assess mRNA profiles.
RESULTS
Eleven genes, such as ALAS2(5-aminolevulinate synthase), SLC4A1(solute carrier family 4 member 1), (hemoglobin subunit gamma 2), (TNF α-induced protein 3), (period circadian clock 1), (coiled-coil domain containing 136), (chromosome 9 open reading frame 84), (interleukin 1β), (FosB protooncogene), (nuclear receptor subfamily 4), (polymerase family member 15), had overlapping expression changes in all 3 cancers of which 3 (, and ) are suggested as potential predictors for the early diagnosis of HT after RT.
CONCLUSIONS
may be useful predictors of HT in patients after RT. Eleven overlapping expression mRNAs among 3 cancers might be potential predictors for early diagnosis of radiation toxicity in patients.
PubMed: 30833875
DOI: 10.1177/1559325819833474 -
Prenatal Diagnosis Aug 2023Unexplained stillbirth is defined as a stillbirth with no known cause after the exclusion of common causes, including obstetric complications, infections, placental... (Review)
Review
Unexplained stillbirth is defined as a stillbirth with no known cause after the exclusion of common causes, including obstetric complications, infections, placental insufficiency or abruption, umbilical cord complications, and congenital abnormalities with or without known genetic cause. More than 60% of stillbirth cases remain unexplained. The aim of this systematic review was to investigate the known genetic causes of unexplained stillbirth cases and to evaluate the current position and future directions for the use of genetic and genomic testing in expanding the knowledge in this field. A systematic search through several databases was performed using the keywords genetics and stillbirths in humans. Different methods to detect various types of causal genetic aberrations have been used in the past decades, from standard karyotyping to novel methods such as chromosomal microarray analysis and next generation sequencing technologies. Apart from common chromosomal aneuploidies, a promising hypothesis about genetic causes included genes related to cardiomyopathies and channelopathies. However, these were tested in the research settings, since molecular karyotyping is currently the standard approach in the routine evaluation of genetic causes of stillbirth. Hereby, we provide evidence that expanding knowledge using novel genetic and genomic testing might uncover new genetic causes of unexplained stillbirth.
Topics: Humans; Female; Pregnancy; Stillbirth; Placenta; Aneuploidy; Databases, Factual; Genetic Profile
PubMed: 37072878
DOI: 10.1002/pd.6354