scholarly journals R577X polymorphism of alpha-actinin-3 in human populations of North-Eastern Asia

2017 ◽  
Vol 15 (1) ◽  
pp. 50
Author(s):  
Boris A Malyarchuk ◽  
Miroslava V Derenko ◽  
Galina A Denisova
Keyword(s):  
Cold Adaptation ◽  
Stop Codon ◽  
Premature Stop Codon ◽  
Muscle Metabolism ◽  
Enzymatic Digestion ◽  
Muscle Performance ◽  
Human Populations ◽  
Eastern Asia ◽  
North East ◽  
North Eastern

Background. In polymorphism rs1815739, a C → T transition converts arginine to a premature stop-codon at residue 577 of the alpha-actinin-3 (ACTN3) protein (R577X polymorphism). This polymorphism may affect muscle performance, and the derived 577X allele has been found to be under-represented in sprint/power athletes. In addition, loss of alpha-actinin-3 results in a shift in muscle metabolism toward the more efficient aerobic pathway, thus pointing that this polymorphism may have been involved in enhancing the capability for hunting and for cold adaptation. Here, we study rs1815739 polymorphism in native populations (Chukchi, Koryaks and Evens) and newcomers (Russians) of North-Eastern Asia. Materials and methods. Genomic DNA was isolated from peripheral blood. ACTN3 genotypes for rs1815739 locus were established by enzymatic digestion of amplicons with DdeI. Heterozygotes TT were confirmed by DNA sequencing. In addition, data on exome variation in Siberian populations were analyzed. Results. Lowered frequencies (less than 40%) of “mutant” allele rs1815739-T were found in studied populations of North-Eastern Asia. Analysis of exome data has shown that haplotype comprising the rs1815739-T allele reaches the highest frequencies in populations of Southern and Central Siberia, while it is rather rare in the north-east of Siberia. Conclusion. The results obtained contradict the hypothesis that the rs1815739 polymorphism may have been involved in cold adaptation of North-East Siberians.

scholarly journals Evolution of the human gastrokine locus and confounding factors regarding the pseudogenicity of GKN3

2013 ◽  
Vol 45 (15) ◽  
pp. 667-683 ◽  
Author(s):  
Jessica H. Geahlen ◽  
Carlo Lapid ◽  
Kaisa Thorell ◽  
Igor Nikolskiy ◽  
Won Jae Huh ◽  
...  
Keyword(s):  
Selective Sweep ◽  
Stop Codon ◽  
Genetic Locus ◽  
Donor Site ◽  
Premature Stop Codon ◽  
Population Based ◽  
Splice Donor Site ◽  
Human Populations ◽  
Selective Sweeps ◽  
Gastric Mucous

In a screen for genes expressed specifically in gastric mucous neck cells, we identified GKN3, the recently discovered third member of the gastrokine family. We present confirmatory mouse data and novel porcine data showing that mouse GKN3 expression is confined to mucous cells of the corpus neck and antrum base and is prominently expressed in metaplastic lesions. GKN3 was proposed originally to be expressed in some human populations and a pseudogene in others. To investigate that hypothesis, we studied human GKN3 evolution in the context of its paralogous genomic neighbors, GKN1 and GKN2. Haplotype analysis revealed that GKN3 mimics GKN2 in patterns of exonic SNP allocation, whereas GKN1 appeared to be more stringently selected. GKN3 showed signatures of both directional selection and population based selective sweeps in humans. One such selective sweep includes SNP rs10187256, originally identified as an ancestral tryptophan to premature STOP codon mutation. The derived (nonancestral) allele went to fixation in Asia. We show that another SNP, rs75578132, identified 5 bp downstream of rs10187256, exhibits a second selective sweep in almost all Europeans, some Latinos, and some Africans, possibly resulting from a reintroduction of European genes during African colonization. Finally, we identify a mutation that would destroy the splice donor site in the putative exon3-intron3 boundary, which occurs in all human genomes examined to date. Our results highlight a stomach-specific human genetic locus, which has undergone various selective sweeps across European, Asian, and African populations and thus reflects geographic and ethnic patterns in genome evolution.

Ectopic Transcript Analysis Indicates that Allelic Exclusion is an Important Cause of Type I Protein C Deficiency in Patients with Nonsense and Frameshift Mutations in the PROC Gene

1996 ◽  
Vol 75 (06) ◽  
pp. 870-876 ◽  
Author(s):  
José Manuel Soria ◽  
Lutz-Peter Berg ◽  
Jordi Fontcuberta ◽  
Vijay V Kakkar ◽  
Xavier Estivill ◽  
...  
Keyword(s):  
Splice Site ◽  
Protein C ◽  
Stop Codon ◽  
Premature Stop Codon ◽  
Allelic Exclusion ◽  
Polymorphism Analysis ◽  
Type I ◽  
Protein C Deficiency ◽  
Nonsense Mutations ◽  
Stop Codons

SummaryNonsense mutations, deletions and splice site mutations are a common cause of type I protein C deficiency. Either directly or indirectly by altering the reading frame, these' lesions generate or may generate premature stop codons and could therefore be expected to result in premature termination of translation. In this study, the possibility that such mutations could instead exert their pathological effects at an earlier stage in the expression pathway, through “allelic exclusion” at the RNA level, was investigated. Protein C (PROC) mRNA was analysed in seven Spanish type I protein C deficient patients heterozygous for two nonsense mutations, a 7bp deletion, a 2bp insertion and three splice site mutations. Ectopic RNA transcripts from patient and control lymphocytes were analysed by RT-PCR and direct sequencing of amplified PROC cDNA fragments. The nonsense mutations and the deletion were absent from the cDNAs indicating that only mRNA derived from the normal allele had been expressed. Similarly for the splice site mutations, only normal PROC cDNAs were obtained. In one case, exclusion of the mutated allele could be confirmed by polymorphism analysis. In contrast to these six mutations, the 2 bp insertion was not associated with loss of mRNA from the mutated allele. In this case, cDNA analysis revealed the absence of 19 bases from the PROC mRNA consistent with the generation and utilization of a cryptic splice site 3’ to the site of mutation, which would result in a frameshift and a premature stop codon. It is concluded that allelic exclusion is a common causative mechanism in those cases of type I protein C deficiency which result from mutations that introduce premature stop codons

The influence of submesoscale eddies on hydrochemical parameters and structural and functional characteristics of phytoplankton in the north-eastern part of the Black Sea

2019 ◽  
pp. 24-40
Author(s):  
Sergey B. Kuklev ◽  
Vladimir A. Silkin ◽  
Valeriy K. Chasovnikov ◽  
Andrey G. Zatsepin ◽  
Larisa A. Pautova ◽  
...  
Keyword(s):  
Anticyclonic Eddy ◽  
The Black Sea ◽  
Hydrochemical Parameters ◽  
North East ◽  
The North ◽  
Seasonal Thermocline ◽  
North Eastern ◽  
Quantitative Indicators ◽  
The City ◽  
North Eastern Part

On June 7, 2018, a sub-mesoscale anticyclonic eddy induced by the wind (north-east) was registered on the shelf in the area of the city of Gelendzhik. With the help of field multidisciplinary expedition ship surveys, it was shown that this eddy exists in the layer above the seasonal thermocline. At the periphery of the eddy weak variability of hydrochemical parameters and quantitative indicators of phytoplankton were recorded. The result of the formation of such eddy structure was a shift in the structure of phytoplankton – the annual observed coccolithophores bloom was not registered.

Late Cretaceous Kholokhovchan floral assemblage of the Okhotsk-Chukotka volcanogenic belt (North-Eastern Asia)

Palaeobotany ◽  
2013 ◽  
Vol 4 ◽  
pp. 116-147 ◽  
Author(s):  
S. V. Shczepetov ◽  
A. B. Herman
Keyword(s):  
Late Cretaceous ◽  
Eastern Asia ◽  
Plant Fossils ◽  
Volcanogenic Belt ◽  
North Eastern ◽  
Volcanogenic Deposits ◽  
Floral Assemblage ◽  
Eastern Russia ◽  
Comprehensive Study

Results of comprehensive study of the Kholokhovchan floral assemblage collection is summarized. These plant fossils were collected in 1978 by E. L. Lebedev from volcanogenic deposits in Penzhina and Oklan rivers interfluve, North-Eastern Russia. This assemblage was previously known as a list of Lebedev’s preliminary identifi cations only. He had suggested that the Kholokhovchan assemblage is correlative to the latest Albian — early Turonian Grebenka flora from the Anadyr River middle reaches. However, our study demonstrates that the Kholokhovchan assemblage is most similar to the presumably the Turonian-Coniacian Arman flora of the Okhotsk-Chukotka volcanogenic belt and, therefore, should be dated as the Turonian-Coniacian or Turonian.

Induction of Translational Readthrough across the Thalassemia-Causing Premature Stop Codon in β-Globin-Encoding mRNA

Biochemistry ◽  
2019 ◽  
Vol 59 (1) ◽  
pp. 80-84 ◽  
Author(s):  
Debaleena Kar ◽  
Karthi Sellamuthu ◽  
Sangeetha Devi Kumar ◽  
Sandeep M. Eswarappa
Keyword(s):  
Stop Codon ◽  
Premature Stop Codon ◽  
Translational Readthrough

scholarly journals A Novel Truncating Mutation in HOMER2 Causes Nonsyndromic Progressive DFNA68 Hearing Loss in a Spanish Family

Genes ◽  
2021 ◽  
Vol 12 (3) ◽  
pp. 411
Author(s):  
María Lachgar ◽  
Matías Morín ◽  
Manuela Villamar ◽  
Ignacio del Castillo ◽  
Miguel Ángel Moreno-Pelayo
Keyword(s):  
Hearing Loss ◽  
Stop Codon ◽  
Coiled Coil ◽  
Premature Stop Codon ◽  
Scaffolding Protein ◽  
Common Mechanism ◽  
Chinese Family ◽  
Truncating Mutation ◽  
Spanish Family ◽  
Sensory Defect

Nonsyndromic hereditary hearing loss is a common sensory defect in humans that is clinically and genetically highly heterogeneous. So far, 122 genes have been associated with this disorder and 50 of them have been linked to autosomal dominant (DFNA) forms like DFNA68, a rare subtype of hearing impairment caused by disruption of a stereociliary scaffolding protein (HOMER2) that is essential for normal hearing in humans and mice. In this study, we report a novel HOMER2 variant (c.832_836delCCTCA) identified in a Spanish family by using a custom NGS targeted gene panel (OTO-NGS-v2). This frameshift mutation produces a premature stop codon that may lead in the absence of NMD to a shorter variant (p.Pro278Alafs*10) that truncates HOMER2 at the CDC42 binding domain (CBD) of the coiled-coil structure, a region that is essential for protein multimerization and HOMER2-CDC42 interaction. c.832_836delCCTCA mutation is placed close to the previously identified c.840_840dup mutation found in a Chinese family that truncates the protein (p.Met281Hisfs*9) at the CBD. Functional assessment of the Chinese mutant revealed decreased protein stability, reduced ability to multimerize, and altered distribution pattern in transfected cells when compared with wild-type HOMER2. Interestingly, the Spanish and Chinese frameshift mutations might exert a similar effect at the protein level, leading to truncated mutants with the same Ct aberrant protein tail, thus suggesting that they can share a common mechanism of pathogenesis. Indeed, age-matched patients in both families display quite similar hearing loss phenotypes consisting of early-onset, moderate-to-profound progressive hearing loss. In summary, we have identified the third variant in HOMER2, which is the first one identified in the Spanish population, thus contributing to expanding the mutational spectrum of this gene in other populations, and also to clarifying the genotype–phenotype correlations of DFNA68 hearing loss.

scholarly journals Cis-Segregation of c.1171C>T Stop Codon (p.R391*) in SERPINC1 Gene and c.1691G>A Transition (p.R506Q) in F5 Gene and Selected GWAS Multilocus Approach in Inherited Thrombophilia

Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 934
Author(s):  
Donato Gemmati ◽  
Giovanna Longo ◽  
Eugenia Franchini ◽  
Juliana Araujo Silva ◽  
Ines Gallo ◽  
...  
Keyword(s):  
At Risk ◽  
Stop Codon ◽  
Association Studies ◽  
Premature Stop Codon ◽  
Large Family ◽  
Genome Wide Association Studies ◽  
Loss Of Function ◽  
Gene Markers ◽  
Inherited Thrombophilia ◽  
Fv Leiden

Inherited thrombophilia (e.g., venous thromboembolism, VTE) is due to rare loss-of-function mutations in anticoagulant factors genes (i.e., SERPINC1, PROC, PROS1), common gain-of-function mutations in procoagulant factors genes (i.e., F5, F2), and acquired risk conditions. Genome Wide Association Studies (GWAS) recently recognized several genes associated with VTE though gene defects may unpredictably remain asymptomatic, so calculating the individual genetic predisposition is a challenging task. We investigated a large family with severe, recurrent, early-onset VTE in which two sisters experienced VTE during pregnancies characterized by a perinatal in-utero thrombosis in the newborn and a life-saving pregnancy-interruption because of massive VTE, respectively. A nonsense mutation (CGA > TGA) generating a premature stop-codon (c.1171C>T; p.R391*) in the exon 6 of SERPINC1 gene (1q25.1) causing Antithrombin (AT) deficiency and the common missense mutation (c.1691G>A; p.R506Q) in the exon 10 of F5 gene (1q24.2) (i.e., FV Leiden; rs6025) were coinherited in all the symptomatic members investigated suspecting a cis-segregation further confirmed by STR-linkage-analyses [i.e., SERPINC1 IVS5 (ATT)5–18, F5 IVS2 (AT)6–33 and F5 IVS11 (GT)12–16] and SERPINC1 intragenic variants (i.e., rs5878 and rs677). A multilocus investigation of blood-coagulation balance genes detected the coexistence of FV Leiden (rs6025) in trans with FV HR2-haplotype (p.H1299R; rs1800595) in the aborted fetus, and F11 rs2289252, F12 rs1801020, F13A1 rs5985, and KNG1 rs710446 in the newborn and other members. Common selected gene variants may strongly synergize with less common mutations tuning potential life-threatening conditions when combined with rare severest mutations. Merging classic and newly GWAS-identified gene markers in at risk families is mandatory for VTE risk estimation in the clinical practice, avoiding partial risk score evaluation in unrecognized at risk patients.

scholarly journals A Review of Recently Discovered Remains of the Pleistocene Branchiopods (Anostraca, Notostraca) from NE Siberia and Arctic Canada

Water ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 280
Author(s):  
D. Christopher Rogers ◽  
Anton A. Zharov ◽  
Anna N. Neretina ◽  
Svetlana A. Kuzmina ◽  
Alexey A. Kotov
Keyword(s):  
Western North America ◽  
Temporary Wetlands ◽  
Indicator Organisms ◽  
Aquatic Habitats ◽  
Eastern Asia ◽  
Large Mammal ◽  
Large Branchiopods ◽  
North Eastern ◽  
North Western ◽  
Large Branchiopod

In this study, we examine, identify, and discuss fossil remains of large branchiopod crustaceans collected from six sites across the Beringian region (north-eastern Asia and north-western North America). Eggs and mandibles from Anostraca and Notostraca, as well as a notostracan telson fragment and a possible notostracan second maxilla, were collected from both paleosediment samples and also from large mammal hair. The remains of large branchiopods and other species that are limited to seasonally astatic aquatic habitats (temporary wetlands) could be useful indicator organisms of paleoecological conditions. Different recent large branchiopod species have very different ecological preferences, with each species limited to specific geochemical component tolerance ranges regarding various salinity, cation, and gypsum concentrations. Our purpose is to bring the potential usefulness of these common fossil organisms to the attention of paleoecologists.

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