scholarly journals mtDNA polymorphism and metabolic inhibition affect sperm performance in conplastic mice

Reproduction ◽  
2017 ◽  
Vol 154 (4) ◽  
pp. 341-354 ◽  
Author(s):  
Maximiliano Tourmente ◽  
Misa Hirose ◽  
Saleh Ibrahim ◽  
Damian K Dowling ◽  
Daniel M Tompkins ◽  
...  
Keyword(s):  
Nuclear Dna ◽  
Reproductive Traits ◽  
Inbred Strains ◽  
Nucleotide Substitutions ◽  
Single Nucleotide ◽  
Atp Production ◽  
Dna Mutations ◽  
Performance Response ◽  
Nuclear Background ◽  
Male Specific

Whereas a broad link exists between nucleotide substitutions in the mitochondrial genome (mtDNA) and a range of metabolic pathologies, exploration of the effect of specific mtDNA genotypes is on-going. Mitochondrial DNA mutations are of particular relevance for reproductive traits, since they are expected to have profound effects on male specific processes as a result of the strict maternal inheritance of mtDNA. Sperm motility is crucially dependent on ATP in most systems studied. However, the importance of mitochondrial function in the production of the ATP necessary for sperm function remains uncertain. In this study, we test the effect of mtDNA polymorphisms upon mouse sperm performance and bioenergetics by using five conplastic inbred strains that share the same nuclear background while differing in their mitochondrial genomes. We found that, while genetic polymorphisms across distinct mtDNA haplotypes are associated with modification in sperm progressive velocity, this effect is not related to ATP production. Furthermore, there is no association between the number of mtDNA polymorphisms and either (a) the magnitude of sperm performance decrease, or (b) performance response to specific inhibition of the main sperm metabolic pathways. The observed variability between strains may be explained in terms of additive effects of single nucleotide substitutions on mtDNA coding sequences, which have been stabilized through genetic drift in the different laboratory strains. Alternatively, the decreased sperm performance might have arisen from the disruption of the nuclear DNA/mtDNA interactions that have coevolved during the radiation ofMus musculussubspecies.

scholarly journals Role of Mitochondrial Genome Mutations in Pathogenesis of Carotid Atherosclerosis

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Margarita A. Sazonova ◽  
Vasily V. Sinyov ◽  
Anastasia I. Ryzhkova ◽  
Elena V. Galitsyna ◽  
Zukhra B. Khasanova ◽  
...  
Keyword(s):  
Mitochondrial Genome ◽  
Carotid Atherosclerosis ◽  
Nuclear Dna ◽  
Nucleotide Substitutions ◽  
Single Nucleotide ◽  
Atherosclerotic Lesions ◽  
Dna Mutations ◽  
Blood Leukocyte ◽  
Study Participants

Mutations of mtDNA, due to their higher frequency of occurrence compared to nuclear DNA mutations, are the most promising biomarkers for assessing predisposition of the occurrence and development of atherogenesis. The aim of the present article was an analysis of correlation of several mitochondrial genome mutations with carotid atherosclerosis. Leukocytes from blood of study participants from Moscow polyclinics were used as research material. The sample size was 700 people. The sample members were diagnosed with “atherosclerosis” on the basis of ultrasonographic examination and biochemical and molecular cell tests. DNA was isolated from blood leukocyte samples of the study participants. PCR fragments of DNA, containing the region of 11 investigated mutations, were pyrosequenced. The heteroplasmy level of these mutations was detected. Statistical analysis of the obtained results was performed using the software package SPSS 22.0. According to the obtained results, an association of mutations m.652delG, m.3336C>T, m.12315G>A, m.14459G>A m.15059G>A with carotid atherosclerosis was found. These mutations can be biomarkers for assessing predisposition to this disease. Additionally, two single nucleotide substitutions (m.13513G>A and m.14846G>A), negatively correlating with atherosclerotic lesions, were detected. These mutations may be potential candidates for gene therapy of atherosclerosis and its risk factors.

scholarly journals The Role of Mitochondria in Carcinogenesis

2021 ◽  
Vol 22 (10) ◽  
pp. 5100
Author(s):  
Paulina Kozakiewicz ◽  
Ludmiła Grzybowska-Szatkowska ◽  
Marzanna Ciesielka ◽  
Jolanta Rzymowska
Keyword(s):  
Prostate Cancer ◽  
Mitochondrial Dna ◽  
Nuclear Dna ◽  
Dna Polymorphisms ◽  
Gene Encoding ◽  
Dna Mutations ◽  
Nadh Ubiquinone Oxidoreductase ◽  
Gene Coi ◽  
The Impact

The mitochondria are essential for normal cell functioning. Changes in mitochondrial DNA (mtDNA) may affect the occurrence of some chronic diseases and cancer. This process is complex and not entirely understood. The assignment to a particular mitochondrial haplogroup may be a factor that either contributes to cancer development or reduces its likelihood. Mutations in mtDNA occurring via an increase in reactive oxygen species may favour the occurrence of further changes both in mitochondrial and nuclear DNA. Mitochondrial DNA mutations in postmitotic cells are not inherited, but may play a role both in initiation and progression of cancer. One of the first discovered polymorphisms associated with cancer was in the gene NADH-ubiquinone oxidoreductase chain 3 (mt-ND3) and it was typical of haplogroup N. In prostate cancer, these mutations and polymorphisms involve a gene encoding subunit I of respiratory complex IV cytochrome c oxidase subunit 1 gene (COI). At present, a growing number of studies also address the impact of mtDNA polymorphisms on prognosis in cancer patients. Some of the mitochondrial DNA polymorphisms occur in both chronic disease and cancer, for instance polymorphism G5913A characteristic of prostate cancer and hypertension.

Single Nucleotide Substitutions Effectively Block Cas9 and Allow for Scarless Genome Editing in Caenorhabditis elegans

2021 ◽  
Author(s):  
Jeffrey C Medley ◽  
Shilpa Hebbar ◽  
Joel T Sydzyik ◽  
Anna Y. Zinovyeva
Keyword(s):  
Caenorhabditis Elegans ◽  
Genome Editing ◽  
Dna Breaks ◽  
Nucleotide Substitutions ◽  
Paternal Genome ◽  
Single Nucleotide ◽  
C Elegans ◽  
Homology Directed Repair ◽  
Maternal Genome ◽  
Guide Sequence

In Caenorhabditis elegans, germline injection of Cas9 complexes is reliably used to achieve genome editing through homology-directed repair of Cas9-generated DNA breaks. To prevent Cas9 from targeting repaired DNA, additional blocking mutations are often incorporated into homologous repair templates. Cas9 can be blocked either by mutating the PAM sequence that is essential for Cas9 activity or by mutating the guide sequence that targets Cas9 to a specific genomic location. However, it is unclear how many nucleotides within the guide sequence should be mutated, since Cas9 can recognize off-target sequences that are imperfectly paired to its guide. In this study, we examined whether single-nucleotide substitutions within the guide sequence are sufficient to block Cas9 and allow for efficient genome editing. We show that a single mismatch within the guide sequence effectively blocks Cas9 and allows for recovery of edited animals. Surprisingly, we found that a low rate of edited animals can be recovered without introducing any blocking mutations, suggesting a temporal block to Cas9 activity in C. elegans. Furthermore, we show that the maternal genome of hermaphrodite animals is preferentially edited over the paternal genome. We demonstrate that maternally provided haplotypes can be selected using balancer chromosomes and propose a method of mutant isolation that greatly reduces screening efforts post-injection. Collectively, our findings expand the repertoire of genome editing strategies in C. elegans and demonstrate that extraneous blocking mutations are not required to recover edited animals when the desired mutation is located within the guide sequence.

Serum alkaline phosphatase activity is regulated by a chromosomal region containing the alkaline phosphatase 2 gene (Akp2) in C57BL/6J and DBA/2J mice

2005 ◽  
Vol 23 (3) ◽  
pp. 295-303 ◽  
Author(s):  
Jennifer E. Foreman ◽  
David A. Blizard ◽  
Glenn Gerhard ◽  
Holly A. Mack ◽  
Dean H. Lang ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Chromosomal Region ◽  
Serum Alkaline Phosphatase ◽  
Inbred Strains ◽  
Lod Score ◽  
Serum Alkaline Phosphatase Activity ◽  
Single Nucleotide ◽  
Significance Level ◽  
Hepatic Expression ◽  
Trait Locus

Quantitative trait locus (QTL) analyses were conducted to identify chromosomal regions that contribute to variability in serum alkaline phosphatase (AP) enzyme activity in mice derived from the C57BL/6J (B6) and DBA/2J (D2) inbred strains. Serum AP was measured in 400 B6D2 F2 mice at 5 mo and 400 B6D2 F2 mice at 15 mo of age that were genotyped at 96 microsatellite markers, and in 19 BXD recombinant inbred (RI) strains at 5 mo of age. A QTL on the distal end of chromosome 4 was present in all sex- and age-specific analyses with a peak logarithm of odds (LOD) score of 20.36 at 58.51 cM. The Akp2 gene, which encodes the major serum AP isozyme, falls within this QTL region at 70.2 cM where the LOD score reached 13.2 (LOD significance level set at 4.3). Serum AP activity was directly related to the number of D2 alleles of a single nucleotide polymorphism in the 5′-flanking region of the Akp2 gene, although no strain-related differences in hepatic expression of Akp2 RNA were found. A variety of sequence polymorphisms in this chromosomal region could be responsible for the differences in serum AP activity; the Akp2 gene, however, with several known amino acid substitutions between protein sequences of the B6 and D2 strains, is a leading candidate.

scholarly journals An exploration of ambigrammatic sequences in narnaviruses

2019 ◽  
Author(s):  
Joseph L. DeRisi ◽  
Greg Huber ◽  
Amy Kistler ◽  
Hanna Retallack ◽  
Michael Wilkinson ◽  
...  
Keyword(s):  
De Novo ◽  
Rna Viruses ◽  
Nucleotide Substitutions ◽  
Rna Dependent Rna Polymerase ◽  
Single Nucleotide ◽  
Reading Frame ◽  
Reverse Complement ◽  
Positive Sense ◽  
Reverse Strand ◽  
Coding Strategy

ABSTRACTNarnaviruses have been described as positive-sense RNA viruses with a remarkably simple genome of ∼ 3 kb, encoding only a highly conserved RNA-dependent RNA polymerase (RdRp). Many narnaviruses, however, are ‘ambigrammatic’ and harbour an additional uninterrupted open reading frame (ORF) covering almost the entire length of the reverse complement strand. No function has been described for this ORF, yet the absence of stops is conserved across diverse narnaviruses, and in every case the codons in the reverse ORF and the RdRp are aligned. The > 3 kb ORF overlap on opposite strands, unprecedented among RNA viruses, motivates an exploration of the constraints imposed or alleviated by the codon alignment. Here, we show that only when the codon frames are aligned can all stop codons be eliminated from the reverse strand by synonymous single-nucleotide substitutions in the RdRp gene, suggesting a mechanism for de novo gene creation within a strongly conserved amino-acid sequence. It will be fascinating to explore what implications this coding strategy has for other aspects of narnavirus biology. Beyond narnaviruses, our rapidly expanding catalogue of viral diversity may yet reveal additional examples of this broadly-extensible principle for ambigrammatic-sequence development.

scholarly journals Association of non-synonymous SNPs of <i>OPN</i> gene with litter size traits in pigs

2015 ◽  
Vol 58 (2) ◽  
pp. 317-323 ◽  
Author(s):  
T. Kumchoo ◽  
S. Mekchay
Keyword(s):  
Litter Size ◽  
Reproductive Traits ◽  
Snp Markers ◽  
Strong Linkage Disequilibrium ◽  
Nucleotide Polymorphisms ◽  
Large White ◽  
Single Nucleotide ◽  
Pcr Rflp ◽  
Polymerase Chain ◽  
Acid Exchange

Abstract. Osteopontin (OPN) gene is a secreted phosphoprotein which appears to play a key function in the conceptus implantation, placentation and maintenance of pregnancy in pigs. The objectives of this study were to verify the non-synonymous single nucleotide polymorphisms (SNPs) and their association with litter size traits in commercial Thai Large White pigs. A total of 320 Thai Large White sows were genotyped using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Three SNPs at c.425G> A, c.573T> C and c.881C> T revealed amino acid exchange rates of p.110Ala> Thr, p.159Val> Ala and p.262Pro> Ser, respectively, and were then segregated. These three SNPs were significantly associated with total number born (TNB) and number born alive (NBA) traits. No polymorphisms of the two SNP markers (c.278A> G and c.452T> G) were observed in this study. Moreover, the SNPs at c.425G> A and c.573T> C were found to be in strong linkage disequilibrium. The association of OPN with litter size emphasizes the importance of porcine OPN as a candidate gene for reproductive traits in pig breeding.

scholarly journals A Novel Distinct Genetic Variant of Tomato Torrado Virus with Substantially Shorter RNA1-Specific 3’untranslated Region (3’UTR)

Plants ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 2454
Author(s):  
Marta Budziszewska ◽  
Przemysław Wieczorek
Keyword(s):  
Amino Acid ◽  
Genetic Variability ◽  
Untranslated Region ◽  
Genetic Variant ◽  
Sequencing Data ◽  
Sequence Analyses ◽  
Nucleotide Substitutions ◽  
Systemic Necrosis ◽  
Single Nucleotide

Tomato torrado virus (ToTV) induces severe systemic necrosis in Solanum lycopersicum. This work aimed at describing the genetic variability of necrosis-inducing ToTV-Wal’17 collected in 2017, derived from the ToTV-Wal’03 after long-term passages in plants. Sequence analyses of the ToTV-Wal’17 indicated twenty-eight single nucleotide substitutions in coding sequence of both RNAs, twelve of which resulted in amino acid changes in viral polyproteins. Moreover the sequencing data revealed that the 3’UTR of ToTV-Wal’17 RNA1 was 394 nts shorter in comparison to Wal’03. The performed sequence analyses revealed that 3’UTR of RNA1 of ToTV-Wal’17 is the most divergent across all previously described European isolates.

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