Allelotyping of Follicular Thyroid Carcinoma: Frequent Allelic Losses in Chromosome Arms 7q, 11p, and 22q

The genetic mechanisms involved in development of follicular thyroid carcinoma are poorly understood, although allelic losses (LOH) in this type of tumor have been reported in small panels of follicular thyroid carcinomas examined in earlier studies. To clarify the real frequency of allelic loss we carried out a genome-wide allelotyping study of 66 follicular thyroid carcinomas using 39 microsatellite markers representing all nonacrocentric autosomal arms. The mean frequency of LOH was 9.2%, and the mean fractional allelic loss was 0.09. The most frequent allelic losses were detected in 7q (28%), 11p (28%), and 22q (41%). When we compared these results with our previous allelotyping studies using identical markers in other types of thyroid cancers, the 9.2% mean frequency of allelic loss detected in follicular thyroid carcinomas was higher than that in papillary thyroid carcinomas (3%), but not as high as that detected in anaplastic thyroid carcinomas (20%). Frequent allelic losses of markers on chromosomes 7q, 11p, and 22q suggest locations to examine for the presence of suppressor genes associated with the development of follicular thyroid carcinoma.

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Comparative transcriptome analysis of mule uncovered several heterosis-related genes for improving muscular endurance and cognition

10.1101/823047 ◽

2019 ◽

Author(s):

Shan Gao

Keyword(s):

Alternative Splicing ◽

Molecular Genetic ◽

Hybrid Vigor ◽

Neuronal System ◽

Future Studies ◽

Genome Wide ◽

A Genome ◽

Genetic Mechanisms ◽

Productive Traits ◽

Genome Wide Gene Expression

AbstractHeterosis has been widely exploited in animal and plant breeding to enhance the productive traits of hybrid progeny of two breeds or two species. Although, there were multiple models for explaining the hybrid vigor, such as dominance and over-dominance hypothesis, its underlying molecular genetic mechanisms remain equivocal. The aim of this study is through comparing the different expression genes (DEGs) and different alternative splicing (DAS) genes to explore the mechanism of heterosis. Here, we performed a genome-wide gene expression and alternative splicing analysis of two heterotic crosses between donkey and horse in three tissues. The results showed that the DAS genes influenced the heterosis-related phenotypes in a unique than DEGs and about 10% DEGs are DAS genes. In addition, over 69.7% DEGs and 87.2% DAS genes showed over-dominance or dominance, respectively. Furthermore, the “Muscle Contraction” and “Neuronal System” pathways were significantly enriched both for the DEGs and DAS genes in muscle. TNNC2 and RYR1 genes may contribute to mule’s great endurance while GRIA2 and GRIN1 genes may be related with mule’s cognition. Together, these DEGs and DAS genes provide the candidates for future studies of the genetic and molecular mechanism of heterosis in mule.

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Clinicopathological and metastasis status of follicular thyroid cancer

Ministry of Science and Technology, Vietnam ◽

10.31276/vjst.63(9).06-09 ◽

2021 ◽

Vol 63 (9) ◽

pp. 6-9

Author(s):

Xuan Hau Nguyen ◽

◽

Thi Phuong Anh Nguyen ◽

Van Quang Le ◽

◽

...

Keyword(s):

Thyroid Cancer ◽

Thyroid Carcinoma ◽

Follicular Thyroid Carcinoma ◽

Nodal Metastasis ◽

Follicular Thyroid Cancer ◽

Male Ratio ◽

Mean Diameter ◽

The Mean ◽

Metastatic Sites ◽

Undetermined Significance

This study aims to evaluate the clinicopathological and metastasis status of follicular thyroid cancer at K Hospital. We conducted a retrospective combined with prospective cohort study of 48 follicular thyroid carcinoma patients treated by surgery at K hospital from January 2016 to July 2020. The mean age was 44±16.1 and the female/male ratio was 4.3/1. Most patients presented with an asymptomatic and had a unilateral tumor with mean diameter was 21.7±12 mm. 72.9% of tumors were classified as TIRADS 4 on ultrasound, and FNA did not play a big role in the diagnosis of follicular thyroid carcinoma with undetermined significance result in 48.9% of cases. Distant metastasis in 18.8%, the most common metastatic sites were bone, followed by the lungs. The overall rate of nodal metastasis was 31.3%. Cancer in both thyroid lobes had significantly associated with nodal metastasis (p<0.05)

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Genome-Wide Histone H3K27 Acetylation Profiling Identified Genes Correlated With Prognosis in Papillary Thyroid Carcinoma

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.682561 ◽

2021 ◽

Vol 9 ◽

Author(s):

Luyao Zhang ◽

Dan Xiong ◽

Qian Liu ◽

Yiling Luo ◽

Yuhan Tian ◽

...

Keyword(s):

Thyroid Carcinoma ◽

Histone Acetylation ◽

Disease Free Survival ◽

Free Survival ◽

Super Enhancer ◽

Genome Wide ◽

A Genome ◽

Histone H3k27 ◽

Benign Thyroid

Thyroid carcinoma (TC) is the most common endocrine malignancy, and papillary TC (PTC) is the most frequent subtype of TC, accounting for 85–90% of all the cases. Aberrant histone acetylation contributes to carcinogenesis by inducing the dysregulation of certain cancer-related genes. However, the histone acetylation landscape in PTC remains elusive. Here, we interrogated the epigenomes of PTC and benign thyroid nodule (BTN) tissues by applying H3K27ac chromatin immunoprecipitation followed by deep sequencing (ChIP-seq) along with RNA-sequencing. By comparing the epigenomic features between PTC and BTN, we detected changes in H3K27ac levels at active regulatory regions, identified PTC-specific super-enhancer-associated genes involving immune-response and cancer-related pathways, and uncovered several genes that associated with disease-free survival of PTC. In summary, our data provided a genome-wide landscape of histone modification in PTC and demonstrated the role of enhancers in transcriptional regulations associated with prognosis of PTC.

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Identification of Genes Regulating Cell Death inStaphylococcus aureus

10.1101/569053 ◽

2019 ◽

Author(s):

Rebecca Yee ◽

Jie Feng ◽

Jiou Wang ◽

Jiazhen Chen ◽

Ying Zhang

Keyword(s):

Cell Death ◽

Acetic Acid ◽

Drug Targets ◽

Opportunistic Pathogen ◽

Infection Model ◽

Chronic Infections ◽

Bacterial Cell Death ◽

Genome Wide ◽

A Genome ◽

Genetic Mechanisms

AbstractStaphylococcus aureusis an opportunistic pathogen that causes acute and chronic infections. Due toS. aureus’ s highly resistant and persistent nature, it is paramount to identify better drug targets in order to eradicateS. aureusinfections. Despite the efforts in understanding bacterial cell death, the genes and pathways ofS. aureuscell death remain elusive. Here, we performed a genome-wide screen using a transposon mutant library to study the genetic mechanisms involved inS. aureuscell death. Using a precisely controlled heat-ramp and acetic acid exposure assays, mutations in 27 core genes (hsdR1, hslO, nsaS, sspA, folD, mfd, vraF, kdpB, USA300HOU_2684, 0868, 0369, 0420, 1154, 0142, 0930, 2590, 0997, 2559, 0044, 2004, 1209, 0152, 2455, 0154, 2386, 0232, 0350 involved in transporters, transcription, metabolism, peptidases, kinases, transferases, SOS response, nucleic acid and protein synthesis) caused the bacteria to be more death-resistant. In addition, we identified mutations in core 10 genes (capA, gltT, mnhG1,USA300HOU_1780, 2496, 0200, 2029, 0336, 0329, 2386, involved in transporters, metabolism, transcription, cell wall synthesis) from heat-ramp and acetic acid that caused the bacteria to be more death-sensitive or with defect in persistence. Interestingly, death-resistant mutants were more virulent than the parental strain USA300 and caused increased mortality in aCaenorhabditis elegansinfection model. Conversely, death-sensitive mutants were less persistent and formed less persister cells upon exposure to different classes of antibiotics. These findings provide new insights into the mechanisms ofS. aureuscell death and offer new therapeutic targets for developing more effective treatments caused byS. aureus.

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The Potential Role of Genetic Assimilation during Maize Domestication

10.1101/105940 ◽

2017 ◽

Cited By ~ 2

Author(s):

Anne Lorant ◽

Sarah Pedersen ◽

Irene Holst ◽

Matthew B. Hufford ◽

Klaus Winter ◽

...

Keyword(s):

Gene Expression ◽

Zea Mays ◽

Potential Role ◽

Expression Patterns ◽

Genetic Assimilation ◽

Genome Wide ◽

A Genome ◽

Genetic Mechanisms ◽

Maize Domestication

ABSTRACTDomestication research has largely focused on identification of morphological and genetic differences between extant populations of crops and their wild relatives. Little attention has been paid to the potential effects of environment despite substantial known changes in climate from the time of domestication to modern day. Recent research, in which maize and teosinte (i.e., wild maize) were exposed to environments similar to the time of domestication, resulted in a plastic induction of domesticated phenotypes in teosinte and little response to environment in maize. These results suggest that early agriculturalists may have selected for genetic mechanisms that cemented domestication phenotypes initially induced by a plastic response of teosinte to environment, a process known as genetic assimilation. To better understand this phenomenon and the potential role of environment in maize domestication, we examined differential gene expression in maize (Zea mays ssp. mays) and teosinte (Zea mays ssp. parviglumis) between past and present conditions. We identified a gene set of over 2000 loci showing a change in expression across environmental conditions in teosinte and invariance in maize. In fact, overall we observed both greater plasticity in gene expression and more substantial re-wiring of expression networks in teosinte across environments when compared to maize. While these results suggest genetic assimilation played at least some role in domestication, genes showing expression patterns consistent with assimilation are not significantly enriched for previously identified domestication candidates, indicating assimilation did not have a genome-wide effect.

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Genome-wide association study reveals the genetic determinism of growth traits in a Gushi-Anka F2 chicken population

Heredity ◽

10.1038/s41437-020-00365-x ◽

2020 ◽

Author(s):

Yanhua Zhang ◽

Yuzhe Wang ◽

Yiyi Li ◽

Junfeng Wu ◽

Xinlei Wang ◽

...

Keyword(s):

Association Study ◽

Genome Wide Association Study ◽

Growth Traits ◽

Carcass Traits ◽

Significant Snps ◽

Genome Wide Association ◽

Pathway Enrichment Analysis ◽

Genome Wide ◽

A Genome ◽

Genetic Mechanisms

Abstract Chicken growth traits are economically important, but the relevant genetic mechanisms have not yet been elucidated. Herein, we performed a genome-wide association study to identify the variants associated with growth traits. In total, 860 chickens from a Gushi-Anka F2 resource population were phenotyped for 68 growth and carcass traits, and 768 samples were genotyped based on the genotyping-by-sequencing (GBS) method. Finally, 734 chickens and 321,314 SNPs remained after quality control and removal of the sex chromosomes, and these data were used to carry out a GWAS analysis. A total of 470 significant single-nucleotide polymorphisms (SNPs) for 43 of the 68 traits were detected and mapped on chromosomes (Chr) 1–6, -9, -10, -16, -18, -23, and -27. Of these, the significant SNPs in Chr1, -4, and -27 were found to be associated with more than 10 traits. Multiple traits shared significant SNPs, indicating that the same mutation in the region might have a large effect on multiple growth or carcass traits. Haplotype analysis revealed that SNPs within the candidate region of Chr1 presented a mosaic pattern. The significant SNPs and pathway enrichment analysis revealed that the MLNR, MED4, CAB39L, LDB2, and IGF2BP1 genes could be putative candidate genes for growth and carcass traits. The findings of this study improve our understanding of the genetic mechanisms regulating chicken growth and carcass traits and provide a theoretical basis for chicken breeding programs.

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Identification of putative markers of triclabendazole resistance by a genome-wide analysis of genetically recombinant Fasciola hepatica

Parasitology ◽

10.1017/s0031182013000528 ◽

2013 ◽

Vol 140 (12) ◽

pp. 1523-1533 ◽

Cited By ~ 31

Author(s):

J. HODGKINSON ◽

K. CWIKLINSKI ◽

N. J. BEESLEY ◽

S. PATERSON ◽

D. J. L. WILLIAMS

Keyword(s):

Genetic Resources ◽

Fasciola Hepatica ◽

Genome Wide Analysis ◽

Extensive Analysis ◽

Genome Wide ◽

A Genome ◽

Genetic Mechanisms ◽

Triclabendazole Resistance

SUMMARYDespite years of investigation into triclabendazole (TCBZ) resistance in Fasciola hepatica, the genetic mechanisms responsible remain unknown. Extensive analysis of multiple triclabendazole-susceptible and -resistant isolates using a combination of experimental in vivo and in vitro approaches has been carried out, yet few, if any, genes have been demonstrated experimentally to be associated with resistance phenotypes in the field. In this review we summarize the current understanding of TCBZ resistance from the approaches employed to date. We report the current genomic and genetic resources for F. hepatica that are available to facilitate novel functional genomics and genetic experiments for this parasite in the future. Finally, we describe our own non-biased approach to mapping the major genetic loci involved in conferring TCBZ resistance in F. hepatica.

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PRICKLE1 × FOCAD Interaction Revealed by Genome-Wide vQTL Analysis of Human Facial Traits

Frontiers in Genetics ◽

10.3389/fgene.2021.674642 ◽

2021 ◽

Vol 12 ◽

Author(s):

Dongjing Liu ◽

Hyo-Jeong Ban ◽

Ahmed M. El Sergani ◽

Myoung Keun Lee ◽

Jacqueline T. Hecht ◽

...

Keyword(s):

Phenotypic Variability ◽

Strong Support ◽

Variable Structure ◽

Cranial Base ◽

Facial Morphology ◽

Genome Wide ◽

A Genome ◽

Trait Variance ◽

Mean Size ◽

The Mean

The human face is a highly complex and variable structure resulting from the intricate coordination of numerous genetic and non-genetic factors. Hundreds of genomic loci impacting quantitative facial features have been identified. While these associations have been shown to influence morphology by altering the mean size and shape of facial measures, their effect on trait variance remains unclear. We conducted a genome-wide association analysis for the variance of 20 quantitative facial measurements in 2,447 European individuals and identified several suggestive variance quantitative trait loci (vQTLs). These vQTLs guided us to conduct an efficient search for gene-by-gene (G × G) interactions, which uncovered an interaction between PRICKLE1 and FOCAD affecting cranial base width. We replicated this G × G interaction signal at the locus level in an additional 5,128 Korean individuals. We used the hypomorphic Prickle1Beetlejuice (Prickle1Bj) mouse line to directly test the function of Prickle1 on the cranial base and observed wider cranial bases in Prickle1Bj/Bj. Importantly, we observed that the Prickle1 and Focadhesin proteins co-localize in murine cranial base chondrocytes, and this co-localization is abnormal in the Prickle1Bj/Bj mutants. Taken together, our findings uncovered a novel G × G interaction effect in humans with strong support from both epidemiological and molecular studies. These results highlight the potential of studying measures of phenotypic variability in gene mapping studies of facial morphology.

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Serial genome-wide sequencing of cell-free DNA (cfDNA) by assays used in non-invasive prenatal testing (NIPT) to identify copy number alterations (CNAs) associated with immunotherapy response.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e14533 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e14533-e14533

Author(s):

Aaron Goodman ◽

Taylor Jensen ◽

Shumei Kato ◽

Christopher Ellison ◽

Lisa Tran ◽

...

Keyword(s):

Cancer Patients ◽

Peripheral Blood ◽

Prenatal Testing ◽

Quantitative Detection ◽

Initial Increase ◽

Continuous Increase ◽

Genome Wide ◽

A Genome ◽

The Mean ◽

Sustained Increase

e14533 Background: cfDNA derived from tumor cells can be detected in the plasma of many cancer patients. Noninvasive methods to detect CNAs have been developed to detect chromosomal abnormalities in the setting of prenatal screening. We hypothesized that similar methods can be used to enable quantitative detection of CNAs in cfDNA, as represented by a genome instability number (GIN), in patients with cancer and used to monitor response to immunotherapy. Methods: Peripheral blood for CNA analysis was collected from patients with diverse cancers for whom immunotherapy was planned. Plasma was separated from peripheral blood using centrifugation. cfDNA was collected and subjected to low-coverage, genome-wide sequencing. CNAs were detected using methods developed for noninvasive prenatal testing. GIN was calculated as the cumulative sum of the deviation from baseline for all detected autosomal CNAs. The current analysis focused on patients with a complete or partial response (CR/PR) or progressive disease (PD). Results: Of 48 patients, 11 (23%) attained CR/PR; 17 (35%), PD; 20, stable disease. Twelve of the 28 patients (43%) with CR/PR (5 (42%)) or PD (7 (58%)) had a GIN value consistent with the presence of CNAs at treatment initiation and ≥ 1 additional sample for comparison. Four of the 5 patients with CR/PR had a decrease in their GIN from their baseline while all 7 patients with PD had a sustained increase in their GIN. The mean (standard error of the mean (SEM)) change in GIN from maximum to minimum for responders was –2753.8 (+/-1643); mean (SEM) change in GIN from minimum to maximum for progressors was 1373.76 (+/-576) (p = 0.0221). Interestingly, 3 of the 5 responders had an initial increase in their GIN after 2-3 weeks of treatment followed by a decline, while all 7 progressors had a continuous increase in their GIN. Conclusions: GIN can be used to monitor response to immune checkpoint inhibitors in cancer patients. Serial evaluation shows an initial GIN increase followed by decline in patients who eventually attain CR/PR, but a sustained increase in patients with progression.

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