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https://www.readbyqxmd.com/read/28734759/nivolumab-in-patients-with-metastatic-dna-mismatch-repair-deficient-or-microsatellite-instability-high-colorectal-cancer-checkmate-142-an-open-label-multicentre-phase-2-study
#1
Michael J Overman, Ray McDermott, Joseph L Leach, Sara Lonardi, Heinz-Josef Lenz, Michael A Morse, Jayesh Desai, Andrew Hill, Michael Axelson, Rebecca A Moss, Monica V Goldberg, Z Alexander Cao, Jean-Marie Ledeine, Gregory A Maglinte, Scott Kopetz, Thierry André
BACKGROUND: Metastatic DNA mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) colorectal cancer has a poor prognosis after treatment with conventional chemotherapy and exhibits high levels of tumour neoantigens, tumour-infiltrating lymphocytes, and checkpoint regulators. All of these features are associated with the response to PD-1 blockade in other tumour types. Therefore, we aimed to study nivolumab, a PD-1 immune checkpoint inhibitor, in patients with dMMR/MSI-H metastatic colorectal cancer...
July 19, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28734069/pathogen-richness-and-abundance-predict-patterns-of-adaptive-mhc-variation-in-insular-amphibians
#2
Supen Wang, Conghui Liu, Anthony B Wilson, Na Zhao, Xianping Li, Wei Zhu, Xu Gao, Xuan Liu, Yiming Li
The identification of the factors responsible for genetic variation and differentiation at adaptive loci can provide important insights into the evolutionary process, and is crucial for the effective management of threatened species. We studied the impact of environmental viral richness and abundance on functional diversity and differentiation of the MHC class Ia locus in populations of the black-spotted pond frog (Pelophylax nigromaculatus), an IUCN-listed species, on 24 land-bridge islands of the Zhoushan Archipelago and 3 nearby mainland sites...
July 22, 2017: Molecular Ecology
https://www.readbyqxmd.com/read/28734064/extensive-seed-and-pollen-dispersal-and-assortative-mating-in-the-rain-forest-tree-entandrophragma-cylindricum-meliaceae-inferred-from-indirect-and-direct-analyses
#3
F K Monthe, O J Hardy, J L Doucet, J Loo, J Duminil
Pollen and seed dispersal are key processes affecting the demographic and evolutionary dynamics of plant species, and are also important considerations for the sustainable management of timber trees. Through direct and indirect genetic analyses we studied the mating system and the extent of pollen and seed dispersal in an economically-important timber species, Entandrophragma cylindricum (Meliaceae). We genotyped adult trees, seeds and saplings from a 400-ha study plot in a natural forest from East Cameroon using eight nuclear microsatellite markers...
July 22, 2017: Molecular Ecology
https://www.readbyqxmd.com/read/28734054/population-demography-and-heterozygosity-fitness-correlations-in-natural-guppy-populations-an-examination-using-sexually-selected-fitness-traits
#4
Catherine E Grueber, John L Fitzpatrick, Alessandro Devigili, Clelia Gasparini, Indar W Ramnarine, Jonathan P Evans
Heterozygosity-fitness correlations (HFCs) have been examined in a wide diversity of contexts, and the results are often used to infer the role of inbreeding in natural populations. Although population demography, reflected in population-level genetic parameters such as allelic diversity or identity disequilibrium, is expected to play a role in the emergence and detectability of HFCs, direct comparisons of variation in HFCs across many populations of the same species, with different genetic histories, are rare...
July 22, 2017: Molecular Ecology
https://www.readbyqxmd.com/read/28734015/different-mir-21-3p-isoforms-and-their-different-features-in-colorectal-cancer
#5
Weijuan Jiao, Xueqin Leng, Qun Zhou, Yayun Wu, Lina Sun, Yan Tan, Hengli Ni, Xiaoqiang Dong, Tong Shen, Yao Liu, Jianming Li
MiR-21, the only miRNA found to be overexpressed in any type of solid tumor, its guide stand, miR-21-5p, has been studied a lot in colorectal cancer (CRC), however, few researchers focused on its passenger strand, miR-21-3p. In this study, based on The Cancer Genome Atlas (TCGA) data, we found that there were more variety and quantity of miR-21-3p isoforms in microsatellite instability (MSI)-type CRC. We further examined the role of miR-21-3p by in vitro and in vivo studies. MiR-21-3p may be an oncogene in CRC by promoting cellular mobility through epithelial-mesenchymal transition (EMT)...
July 22, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28730763/dna-mismatch-repair-deficiency-in-lung-and-oral-cavity-carcinomas-the-role-of-histogenetic-origin
#6
Konstantina N Spetsotaki, Evangelos Tsiambas, Athanasios Stamatelopoulos, Panagiotis P Fotiades, Ioannis Kastanioudakis, Pericles Tomos, Vasileios Ragos
DNA mismatch repair system (DNA MMR) is a crucial genetic mechanism for DNA homeostasis in prokaryotic and eukaryotic cells. During DNA replication and also recombination, point intra-nucleotide errors including base deletion, insertion, and mis-incorporation happen. These raised abnormalities in the newly synthesized DNA strand could affect negatively the stability of the molecule and the function of the corresponding genes. DNA MMR proteins prevent these errors by recognizing and repairing them, securing directly the normal anatomy of the DNA double strand and indirectly the expression of the genes...
May 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/28730668/recurrent-triploid-digynic-conceptions-and-mature-ovarian-teratomas-are-they-different-manifestations-of-the-same-genetic-defect
#7
Yassemine Khawajkie, William Buckett, Ngoc Minh Phuong Nguyen, Nawel Mechtouf, Asangla Ao, Jocelyne Arseneau, Rima Slim
Miscarriages affect 15% of clinically recognized pregnancies. Recurrent miscarriage (RM) is defined by the occurrence of at least two consecutive pregnancy losses and affects 1% to 5% of couples trying to conceive. In an attempt to categorize patients with RM and identify the mechanisms leading to their miscarriages, we first used flow cytometry to assess the ploidy of 93 products of conception (POCs) from 53 patients with RM (≥ 3 miscarriages). We identified a single patient with four triploid POCs. We then used fluorescent in situ hybridization to confirm the triploidies and fluorescent microsatellite genotyping with distal and pericentromeric markers to determine their parental origin and the mechanisms leading to their formation...
July 21, 2017: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/28729957/decline-of-heterozygosity-in-a-large-but-isolated-population-a-45-year-examination-of-moose-genetic-diversity-on-isle-royale
#8
Renae L Sattler, Janna R Willoughby, Bradley J Swanson
Wildlife conservation and management approaches typically focus on demographic measurements to assess population viability over both short and long periods. However, genetic diversity is an important predictor of long term population vitality. We investigated the pattern of change in genetic diversity in a large and likely isolated moose (Alces alces) population on Isle Royale (Lake Superior) from 1960-2005. We characterized samples, partitioned into five different 5-year periods, using nine microsatellite loci and a portion of the mtDNA control region...
2017: PeerJ
https://www.readbyqxmd.com/read/28729953/demographic-inference-through-approximate-bayesian-computation-skyline-plots
#9
Miguel Navascués, Raphaël Leblois, Concetta Burgarella
The skyline plot is a graphical representation of historical effective population sizes as a function of time. Past population sizes for these plots are estimated from genetic data, without a priori assumptions on the mathematical function defining the shape of the demographic trajectory. Because of this flexibility in shape, skyline plots can, in principle, provide realistic descriptions of the complex demographic scenarios that occur in natural populations. Currently, demographic estimates needed for skyline plots are estimated using coalescent samplers or a composite likelihood approach...
2017: PeerJ
https://www.readbyqxmd.com/read/28729869/genetic-patterns-of-myrceugenia-correifolia-a-rare-species-of-fog-dependent-forests-of-mediterranean-chile-is-it-a-climatic-relict
#10
Fernanda Pérez, Luis F Hinojosa, Gioconda Peralta, Paz Montenegro, Carla Irarrázabal, Michel Cossio
Rare species frequently occur in areas with microclimatic conditions that are atypical for their regions, but that were more common in the past, and that probably have operated as climatic refugia for a long time. Myrceugenia correifolia is a rare arboreal species that grows in deep canyons and hilltops of the Coast Range of north-central Chile between 30° and 35°S. In the northern edge of its distribution M. correifolia grows in small patches of fog-dependent forest surrounding by xeric vegetation. These forest formations are thought to be remnants of an ancient and continuous rainforest that according to some authors became fragmented during aridization of the Neogene (Neogene relict) and to others during warm-dry cycles of the Pleistocene (glacial relicts)...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28729554/comparison-of-traditional-and-new-generation-dna-markers-declares-high-genetic-diversity-and-differentiated-population-structure-of-wild-almond-species
#11
Karim Sorkheh, Mehrana Koohi Dehkordi, Sezai Ercisli, Attila Hegedus, Júlia Halász
Wild almond species as sources of genetic variation may have crucial importance in breeding. A total of 389 accessions of 18 species have been analysed using inter-retrotransposon amplified polymorphism (IRAP), retrotransposon-microsatellite amplified polymorphism (REMAP), sequence-specific amplification polymorphism (S-SAP), amplified fragment length polymorphism (AFLP), inter simple sequence repeat (ISSR) and simple sequence repeats (SSR). Retrotransposon markers indicated the presence and movement of some Ty3-gypsy and Ty1-copia-elements in almond genome...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28728588/genetic-structure-and-gene-flow-of-the-flea-xenopsylla-cheopis-in-madagascar-and-mayotte
#12
Mireille Harimalala, Sandra Telfer, Hélène Delatte, Phillip C Watts, Adélaïde Miarinjara, Tojo Rindra Ramihangihajason, Soanandrasana Rahelinirina, Minoarisoa Rajerison, Sébastien Boyer
BACKGROUND: The flea Xenopsylla cheopis (Siphonaptera: Pulicidae) is a vector of plague. Despite this insect's medical importance, especially in Madagascar where plague is endemic, little is known about the organization of its natural populations. We undertook population genetic analyses (i) to determine the spatial genetic structure of X. cheopis in Madagascar and (ii) to determine the potential risk of plague introduction in the neighboring island of Mayotte. RESULTS: We genotyped 205 fleas from 12 sites using nine microsatellite markers...
July 20, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/28728506/microsatellite-instability-and-promoter-hypermethylation-of-dna-repair-genes-in-hematologic-malignancies-a-forthcoming-direction-toward-diagnostics
#13
Priyanjali Bhattacharya, Trupti N Patel
OBJECTIVE: The objective of our review is to highlight the significance of microsatellite hypervariation in diagnostics of hematologic malignancies. METHODS: For the past few decades, extensive experiments in cancer research have explored all the possible pathways and a number of deleterious mutations that either make the tumor suppressor genes (TSGs) dysfunctional or cause the proto-oncogenes to behave abnormally by changing the cellular phenotype hence rendering disease...
July 20, 2017: Hematology (Amsterdam, Netherlands)
https://www.readbyqxmd.com/read/28727488/microsatellites-mapping-for-non-model-species-with-chromosomal-rearrangement-a-case-study-in-the-frog-quasipaa-boulengeri-anura-dicroglossidae
#14
Xiuyun Yuan, Siqi Yuan, Ya Liu, Yun Xia, Xiaomao Zeng
Gene mapping is an important resource for understanding the evolution of genes and cytogenetics. Model species with a known genetic map or genome sequence allow for the selection of genetic markers on a desired chromosome, while it is hard to locate these markers on chromosomes of non-model species without such references. A frog species, Quasipaa boulengeri, shows chromosomal rearrangement polymorphisms, making itself a fascinating model for chromosomal speciation mediated by suppressed recombination. However, no markers have been located on its rearranged chromosomes...
July 20, 2017: Genome Génome / Conseil National de Recherches Canada
https://www.readbyqxmd.com/read/28727142/genomic-and-transcriptomic-heterogeneity-of-colorectal-tumors-arising-in-lynch-syndrome
#15
Hans Binder, Lydia Hopp, Michal R Schweiger, Steve Hoffmann, Frank Jühling, Martin Kerick, Bernd Timmermann, Susann Siebert, Christina Grimm, Lilit Nersisyan, Arsen Arakelyan, Maria Herberg, Peter Buske, Henry Loeffler-Wirth, Maciej Rosolowski, Christoph Engel, Jens Przybilla, Martin Peifer, Nicolaus Friedrichs, Gabriela Moeslein, Margarete Odenthal, Michelle Hussong, Sophia Peters, Stefanie Holzapfel, Jacob Nattermann, Robert Hueneburg, Wolff Schmiegel, Brigitte Royer-Pokora, Stefan Aretz, Michael Kloth, Matthias Kloor, Reinhard Buettner, Jörg Galle, Markus Loeffler
Colorectal cancer (CRC) arising in Lynch Syndrome (LS) comprises tumors with constitutional mutations in DNA mismatch-repair genes. Whole-genome and transcriptome studies of LS-CRC are still missing to address questions about similarities and differences of mutation and gene expression characteristics between LS-CRC and sporadic CRC, about the molecular heterogeneity of LS-CRC and about specific mechanisms of LS-CRC genesis linked to dysfunctional mismatch-repair in LS colonic mucosa and the possible role of immune editing...
July 20, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28727001/analysis-of-genetic-diversity-of-chinese-dairy-goats-via-microsatellite-markers
#16
G Z Wang, S S Chen, T L Chao, Z B Ji, L Hou, Z J Qin, J M Wang
In this study, 15 polymorphic microsatellite markers were used to analyze the genetic structure and phylogenetic relationships of 6 dairy goat breeds in China, including 4 native developed breeds and 2 introduced breeds. The results showed that a total of 172 alleles were detected in 347 samples of the dairy goat breeds included in this study. The mean number of effective alleles per locus was 4.92. Except for BMS0812, all of the remaining microsatellite loci were highly polymorphic (polymorphism information content [PIC] > 0...
May 2017: Journal of Animal Science
https://www.readbyqxmd.com/read/28725387/origins-of-two-hemiclonal-hybrids-among-three-hexagrammos-species-teleostei-hexagrammidae-genetic-diversification-through-host-switching
#17
Hiroyuki Munehara, Miho Horita, Motoko R Kimura-Kawaguchi, Aya Yamazaki
Two natural, hemiclonal hybrid strains were discovered in three Hexagrammos species. The natural hybrids, all of which were females that produced haploid eggs containing only the Hexagrammos octogrammus genome (maternal ancestor; hereafter Hoc), generated F1 hybrid-type offspring by fertilization with haploid sperm of Hexagrammos agrammus or Hexagrammos otakii (paternal species; Hag and Hot, respectively). This study was performed to clarify the extent of diversification between the two hybrids and the maternal ancestor...
October 2016: Ecology and Evolution
https://www.readbyqxmd.com/read/28723952/evidence-for-prehistoric-origins-of-the-g2019s-mutation-in-the-north-african-berber-population
#18
Rafiqua Ben El Haj, Ayyoub Salmi, Wafa Regragui, Ahmed Moussa, Naima Bouslam, Houyam Tibar, Ali Benomar, Mohamed Yahyaoui, Ahmed Bouhouche
The most common cause of the monogenic form of Parkinson's disease known so far is the G2019S mutation of the leucine-rich repeat kinase 2 (LRRK2) gene. Its frequency varies greatly among ethnic groups and geographic regions ranging from less than 0.1% in Asia to 40% in North Africa. This mutation has three distinct haplotypes; haplotype 1 being the oldest and most common. Recent studies have dated haplotype 1 of the G2019S mutation to about 4000 years ago, but it remains controversial whether the mutation has a Near-Eastern or Moroccan-Berber ancestral origin...
2017: PloS One
https://www.readbyqxmd.com/read/28722587/lack-of-geospatial-population-structure-yet-significant-linkage-disequilibrium-in-the-reservoir-of-plasmodium-falciparum-in-bongo-district-ghana
#19
Shazia Ruybal-Pesántez, Kathryn E Tiedje, Mary M Rorick, Lucas Amenga-Etego, Anita Ghansah, Abraham Oduro, Kwadwo A Koram, Karen P Day
Malaria control in West Africa is impeded by the large reservoir of chronic asymptomatic Plasmodium falciparum infections in the human population. This study aimed to assess the extent of diversity in the P. falciparum reservoir in Bongo District (BD), Ghana, at the end of the dry season, the lowest point in malaria transmission over the course of the year. Analysis of the variation in 12 microsatellite loci was completed for 200 P. falciparum isolates collected from a cross-sectional survey of residents of all ages from two catchment areas in BD...
July 3, 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/28720156/fmr1-cgg-repeat-expansion-mutation-detection-and-linked-haplotype-analysis-for-reliable-and-accurate-preimplantation-genetic-diagnosis-of-fragile-x-syndrome
#20
Indhu-Shree Rajan-Babu, Mulias Lian, Felicia S H Cheah, Min Chen, Arnold S C Tan, Ethiraj B Prasath, Seong Feei Loh, Samuel S Chong
Fragile X mental retardation 1 (FMR1) full-mutation expansion causes fragile X syndrome. Trans-generational fragile X syndrome transmission can be avoided by preimplantation genetic diagnosis (PGD). We describe a robust PGD strategy that can be applied to virtually any couple at risk of transmitting fragile X syndrome. This novel strategy utilises whole-genome amplification, followed by triplet-primed polymerase chain reaction (TP-PCR) for robust detection of expanded FMR1 alleles, in parallel with linked multi-marker haplotype analysis of 13 highly polymorphic microsatellite markers located within 1 Mb of the FMR1 CGG repeat, and the AMELX/Y dimorphism for gender identification...
July 19, 2017: Expert Reviews in Molecular Medicine
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