A hemizygous GYG2 mutation and Leigh syndrome: a possible link?

Leigh syndrome (LS) is an early-onset progressive neurodegenerative disorder characterized by unique, bilateral neuropathological findings in brainstem, basal ganglia, cerebellum and spinal cord. LS is genetically heterogeneous, with the majority of the causative genes affecting mitochondrial malfunction, and many cases still remain unsolved. Here, we report male sibs affected with LS showing ketonemia, but no marked elevation of lactate and pyruvate. To identify their genetic cause, we performed whole exome sequencing. Candidate variants were narrowed down based on autosomal recessive and X-linked recessive models. Only one hemizygous missense mutation (c.665G>C, p.W222S) in glycogenin-2 (GYG2) (isoform a: NM_001079855) in both affected sibs and a heterozygous change in their mother were identified, being consistent with the X-linked recessive trait. GYG2 encodes glycogenin-2 (GYG2) protein, which plays an important role in the initiation of glycogen synthesis. Based on the structural modeling, the mutation can destabilize the structure and result in protein malfunctioning. Furthermore, in vitro experiments showed mutant GYG2 was unable to undergo the self-glucosylation, which is observed in wild-type GYG2. This is the first report of GYG2 mutation in human, implying a possible link between GYG2 abnormality and LS.     

Molecular epidemiological characterization of Staphylococcus aureus isolates originating from food poisoning outbreaks that occurred in Tokyo,Japan

Staphylococcal food poisoning (SFP), one of the commonest food‐borne diseases, results from the ingestion of one or more staphylococcal enterotoxins (SEs) produced in foods by Staphylococcus aureus. In the present study, 203 S. aureus strains originating from 83 outbreaks that had occurred in Tokyo were examined for their coagulase type and genotype of SEs to analyze their molecular epidemiological characteristics. The representative subsets of the 83 S. aureus isolates were analyzed by multilocus sequence typing (MLST) and S. aureus pathogenicity island (SaPI) scanning. The isolates were integrated into eight specific clonal complexes (CC) s; CC81, CC8, CC6, CC5, CC508, CC59, CC20 and CC30. The profiles of the coagulase type, SE/SEl genotype and the suspected type of enterotoxin‐encoding mobile genetic element (MGE) indicated a correlation with each CC. SaPI scanning showed fixed regularity between the distributions of genomic islands, including SaPIs, and the phylogenetic lineage based on MLST. These results indicate that the S. aureus isolates, which classified into eight CCs, have distinguishable properties concerning specific coagulase type, enterotoxin genotype and MGE type. Strains of S. aureus harboring these particular elements possess the potential to cause SFP.     

Prevalence of human T‐lymphotropic virus type 1 carriers among pregnant women in Hokkaido,Japan

As there is a risk of MTCT of HTLV‐1, the HSGP HTLV‐1 MTCT was organized in 2011. To determine how many pregnant women are infected with HTLV‐1 in Hokkaido, which is the northernmost and the second largest island in Japan with a population of 5 467 000 and 39 392 newborns in 2011, the HSGP HTLV‐1 MTCT asked all facilities that may care for pregnant women in Hokkaido in July 2013 to provide information on the number of pregnant women who underwent screening for anti‐HTLV‐1 antibody using particle agglutination or chemiluminescent enzyme immunoassay, and the numbers of those with positive, equivocal, and negative test results in the screening and confirmation tests using western blotting or PCR methods in 2012, respectively. A total of 111 facilities participated in this study and provided information on 33 617 pregnant women who underwent screening in 2012, corresponding to approximately 85% of all pregnant women who gave birth in Hokkaido in 2012. Of 81 candidates for a confirmation test because of positive (n = 77) or equivocal (n = 4) results on screening, 63 (78%) underwent the confirmation test and, finally, 34 (0.1%) and 33 563 (99.8%) women were judged to be HTLV‐1 carriers and non‐carriers, respectively. It was concluded that the prevalence rate of HTLV‐1 carriers was low, one per 1000 pregnant women in Hokkaido. Approximately 40 infants are born yearly to mothers infected with HTLV‐1 in Hokkaido.     

Concentration of Sec12 at ER exit sites via interaction with cTAGE5 is required for collagen export

Mechanisms for exporting variably sized cargo from the endoplasmic reticulum (ER) using the same machinery remain poorly understood. COPII-coated vesicles, which transport secretory proteins from the ER to the Golgi apparatus, are typically 60–90 nm in diameter. However, collagen, which forms a trimeric structure that is too large to be accommodated by conventional transport vesicles, is also known to be secreted via a COPII-dependent process. In this paper, we show that Sec12, a guanine-nucleotide exchange factor for Sar1 guanosine triphosphatase, is concentrated at ER exit sites and that this concentration of Sec12 is specifically required for the secretion of collagen VII but not other proteins. Furthermore, Sec12 recruitment to ER exit sites is organized by its direct interaction with cTAGE5, a previously characterized collagen cargo receptor component, which functions together with TANGO1 at ER exit sites. These findings suggest that the export of large cargo requires high levels of guanosine triphosphate–bound Sar1 generated by Sec12 localized at ER exit sites.     

FGFR1-Frs2/3 Signalling Maintains Sensory Progenitors during Inner Ear Hair Cell Formation

Inner ear mechanosensory hair cells transduce sound and balance information. Auditory hair cells emerge from a Sox2-positive sensory patch in the inner ear epithelium, which is progressively restricted during development. This restriction depends on the action of signaling molecules. Fibroblast growth factor (FGF) signalling is important during sensory specification: attenuation of Fgfr1 disrupts cochlear hair cell formation; however, the underlying mechanisms remain unknown. Here we report that in the absence of FGFR1 signaling, the expression of Sox2 within the sensory patch is not maintained. Despite the down-regulation of the prosensory domain markers, p27^Kip1, Hey2, and Hes5, progenitors can still exit the cell cycle to form the zone of non-proliferating cells (ZNPC), however the number of cells that form sensory cells is reduced. Analysis of a mutant Fgfr1 allele, unable to bind to the adaptor protein, Frs2/3, indicates that Sox2 maintenance can be regulated by MAP kinase. We suggest that FGF signaling, through the activation of MAP kinase, is necessary for the maintenance of sensory progenitors and commits precursors to sensory cell differentiation in the mammalian cochlea.     

The Genome Landscape of the African Green Monkey Kidney-Derived Vero Cell Line

Continuous cell lines that originate from mammalian tissues serve as not only invaluable tools for life sciences, but also important animal cell substrates for the production of various types of biological pharmaceuticals. Vero cells are susceptible to various types of microbes and toxins and have widely contributed to not only microbiology, but also the production of vaccines for human use. We here showed the genome landscape of a Vero cell line, in which 25,877 putative protein-coding genes were identified in the 2.97-Gb genome sequence. A homozygous ∼9-Mb deletion on chromosome 12 caused the loss of the type I interferon gene cluster and cyclin-dependent kinase inhibitor genes in Vero cells. In addition, an ∼59-Mb loss of heterozygosity around this deleted region suggested that the homozygosity of the deletion was established by a large-scale conversion. Moreover, a genomic analysis of Vero cells revealed a female Chlorocebus sabaeus origin and proviral variations of the endogenous simian type D retrovirus. These results revealed the genomic basis for the non-tumourigenic permanent Vero cell lineage susceptible to various pathogens and will be useful for generating new sub-lines and developing new tools in the quality control of Vero cells.     

Sequence Analysis of the Genome of Carnation (Dianthus caryophyllus L.)

The whole-genome sequence of carnation (Dianthus caryophyllus L.) cv. ‘Francesco’ was determined using a combination of different new-generation multiplex sequencing platforms. The total length of the non-redundant sequences was 568 887 315 bp, consisting of 45 088 scaffolds, which covered 91% of the 622 Mb carnation genome estimated by k-mer analysis. The N50 values of contigs and scaffolds were 16 644 bp and 60 737 bp, respectively, and the longest scaffold was 1 287 144 bp. The average GC content of the contig sequences was 36%. A total of 1050, 13, 92 and 143 genes for tRNAs, rRNAs, snoRNA and miRNA, respectively, were identified in the assembled genomic sequences. For protein-encoding genes, 43 266 complete and partial gene structures excluding those in transposable elements were deduced. Gene coverage was ∼98%, as deduced from the coverage of the core eukaryotic genes. Intensive characterization of the assigned carnation genes and comparison with those of other plant species revealed characteristic features of the carnation genome. The results of this study will serve as a valuable resource for fundamental and applied research of carnation, especially for breeding new carnation varieties. Further information on the genomic sequences is available at http://carnation.kazusa.or.jp.     

Generation and Characterization of Ins1-cre-driver C57BL/6N for Exclusive Pancreatic Beta Cell-specific Cre-loxP Recombination

Cre/loxP system-mediated site-specific recombination is utilized to study gene function in vivo. Successful conditional knockout of genes of interest is dependent on the availability of Cre-driver mice. We produced and characterized pancreatic β cell-specific Cre-driver mice for use in diabetes mellitus research. The gene encoding Cre was inserted into the second exon of mouse Ins1 in a bacterial artificial chromosome (BAC). Five founder mice were produced by microinjection of linearized BAC Ins1-cre. The transgene was integrated between Mafa and the telomere on chromosome 15 in one of the founders, BAC Ins1-cre25. To investigate Cre-loxP recombination, BAC Ins1-cre25 males were crossed with two different Cre-reporters, R26R and R26GRR females. On gross observation, reporter signal after Cre-loxP recombination was detected exclusively in the adult pancreatic islets in both F₁ mice. Immunohistological analysis indicated that Cre-loxP recombination-mediated reporter signal was colocalized with insulin in pancreatic islet cells of both F₁ mice, but not with glucagon. Moreover, Cre-loxP recombination signal was already observed in the pancreatic islets at E13.5 in both F₁ fetuses. Finally, we investigated ectopic Cre-loxP recombination for Ins1, because the ortholog Ins2 is also expressed in the brain, in addition to the pancreas. However, there was no Cre-loxP recombination-mediated reporter signal in the brain of both F₁ mice. Our data suggest that BAC Ins1-cre25 mice are a useful Cre-driver C57BL/6N for pancreatic β cell-specific Cre-loxP recombination, except for crossing with knock-in mice carrying floxed gene on chromosome 15.     

Transgenerational epigenetic information through the sperm: Sperm cells not just merely supply half of the genome for new life; they also seem to transmit additional information via epigenetic modifications

The biological cause for the increase in Autism Spectrum Disorder may be fathers’ older age and the epigenetic marks it leaves on sperm cells. Subject Categories: Chromatin, Epigenetics, Genomics & Functional Genomics, Development & Differentiation, Ecology

COVID‐19 is not the only pandemic that is affecting an increasing number of people; autism spectrum disorder (ASD) is another ongoing pandemic that has attracted much less attention despite the fact that its prevalence is rapidly increasing. Between 1975 and 2009, the frequency of ASD in the United States increased from 1/5,000 to 1/110, and the US Centers for Disease Control and Prevention recently reported an incidence as high as 1/54 (see “Further reading”). This is not confined to the United States of course but the same trend can be observed in other countries as well. One possible explanation for this dramatic increase in ASD is the change of diagnostic criteria. These were established in the 1980s and have since been expanded to include milder forms of autism. Along with more public awareness of ASD and more cases being recognized as such, this would explain, at least in part, the increasing number of affected children, but social and diagnostic factors are not sufficient to explain the rise of ASD: there must also be biological factors at play. Indeed, various epidemiological studies suggest that the age of the parents, in particular the father’s age, is an important risk factor.The age at childbirth is related to socioeconomic issues: longer education or higher costs for raising and educating children correlate with older parental age. In addition, assisted reproductive technologies are further increasing the age of birth as this helps women to delay motherhood until into their late 30s or even 40s. However, as both reproductive capacity and the quality of germline cells decline with age, older age at childbirth is associated with lower pregnancy rates, increased risk of miscarriage, and higher risk of various diseases and disorders for the children.     

Induction of (6-4) photolyase gene transcription by blue light in Xenopus A6 cells

(6-4) photolyase repairs pyrimidine-pyrimidone (6-4) photoproducts generated in DNA upon UV light exposure. We studied the effects of blue light on the expression of this gene in Xenopus A6 cells. Exposure of the cells to blue light, but not red light, for 12 h resulted in more than 20-fold increase of the (6-4) photolyase mRNA. By contrast, levels of the other two photolyase mRNAs, i.e., those for CPD photolyase and cryptochrome DASH, did not change significantly. Oxygen radicals presumably generated within the cells upon exposure to blue light were not the cause of the induction, since addition of neither hydrogen peroxide nor a photosensitizer, phenol red, in the culture medium increased the (6-4) photolyase mRNA level. These results support the possibility that the expression of (6-4) photolyase may be regulated by a mechanism involving an as yet ill-defined blue light photoreceptor in the peripheral tissues of Xenopus.