Journal of Genetics最新文献

In the fruit fly Drosophila melanogaster, circadian rhythm was disrupted when the inner nuclear membrane protein lamin B receptor (LBR) was depleted from its clock neurons (Proc. Natl. Acad. Sci. USA 118, e2019756118. 2021; https://doi.org/10. 1073/pnas.2019756118 and Research 6, 0139, 2023; https://doi.org/10.34133/research.0139). Ordinarily, the clock proteinPERIOD (PER) forms foci close to the inner nuclear membrane in the circadian clock's repression phase. The size, number, and location of foci near the nuclear membrane oscillate with a 24-h rhythm. When LBR was absent the foci did not form. The PER foci bring per and other clock genes close to the nuclear envelope, where their transcription is silenced. Then, in the circadian clock's activation phase, the PER protein gradually gets degraded and the foci disappear. The clock genes, including per, relocate to the nucleus interior where they resume transcription. Rhythmic re-positioning of clock genes between nucleus periphery and interior, correlates with their repression and activation in the circadian cycle. Absence of LBR disrupted this rhythm. Phosphorylation of PER promoted the formation of foci whereas dephosphorylation by protein phosphatase 2A causedthem to disappear. LBR promoted focus formation by destabilizing the catalytic subunit of protein phosphatase 2A. The lbr gene is no stranger to this journal. The first hint that vertebrate LBR is also a sterol biosynthesis enzyme, specifically, a sterol C14 reductase, was reported here (J. Genet. 73, 33-41, 1994; https://www.ias.ac.in/article/fulltext/jgen/073/01/0033-0041). Mutations in the human Lbr gene cause a range of phenotypes--from the relatively benign Pelger-Huet anomaly to the perinatally lethal Greenberg skeletal dysplasia.Drosophila, like all insects, is a sterol auxotroph. The fly orthologue of vertebrate lbr genes encodes a protein (dLBR) that shares several properties with vertebrate LBR proteins, with one notable exception. While human LBR complemented theyeast Saccharomyces cerevisiae erg24 mutant which lacks sterol C14 reductase activity, dLBR did not (J. Cell. Sci. 117, 2015-28, 2004; https://doi.org/10.1242/jcs.01052). Despite not possessing sterol reductase activity, dLBR retains significant sequence homology with vertebrate LBRs which have this activity. An undergraduate summer trainee in my laboratory obtained early (unpublished) evidence that dLBR lost sterol reductase activity during evolution. She transferred adult drosophila flies to vials containing a medium made of agar, dextrose, and dried and powdered mycelium of the filamentous fungus Neurospora crassa. On medium made with wild-type mycelium, theflies mated, laid eggs, hatched larvae, and developed pupae which eclosed progeny adult flies. The life cycle was no different than on 'regular' fly food composed of agar, dextrose and yeast extract. However, on a medium made with my

Fixation index (F_st) statistics provide critical insights into evolutionary processes affecting the structure of genetic variation within and among populations. F_st statistics have been widely applied in population and evolutionary genetics to identify genomic regions targeted by selection pressures. The FSTest 1.3 software was developed to estimate four F_st statistics of Hudson, Weir and Cockerham, Nei, and Wright using high-throughput genotyping or sequencing data. Here, we introduced FSTest 1.3 and compared its performance with two widely used software VCFtools 0.1.16 and PLINK 2.0. Chromosome 1 of 1000 Genomes Phase III variant data belonging to South Asian (n = 211) and African (n = 274) populations were included as an example case in this study. Different F_st estimates were calculated for each single-nucleotide polymorphism (SNP) in a pairwise comparison of South Asian against African populations, and the results of FSTest 1.3 were confirmed by VCFtools 0.1.16 and PLINK 2.0. Two different sliding window approaches, one based on a fixed number of SNPs and another based on a fixed number of base pair (bp) were conducted using FSTest 1.3 and VCFtools 0.1.16. Our results showed that regions with low coverage genotypic data could lead to an overestimation of F_st in sliding window analysis using a fixed number of bp. FSTest 1.3 could mitigate this challenge by estimating the average of consecutive SNPs along the chromosome. FSTest 1.3 allows direct analysis of VCF files with a small amount of code and can calculate F_st estimates on a desktop computer for more than a million SNPs in a few minutes. FSTest 1.3 is freely available at https://github.com/similab/FSTest.

We present here the complete mitochondrial sequence of the critically endangered Malaysian giant turtle, Orlitia borneensis. The assembled mitochondrial genome includes 13 protein-coding genes (PCGs), 22 transfer RNA (tRNA) genes, two ribosomal RNA genes (rRNAs), and one control region. This mitochondrial genome has been archived in the NCBI GenBank with accession number OQ808845. The Batagur control region is relatively smaller than O. borneensis and closer to Aldabrachelys gigantea, which suggests potentially that O. borneensis has undergone an expansion in the control region.

The genus Indotyphlops has a widespread distribution in the Indian landmass and Southeast Asia, with 20 reported species. The current classification within the genus is based on morphology. In this study, we sampled all the reported Indotyphlops species from subcontinental India, to resolve relationships within this genus and to understand biogeographic patterns that resulted in the widespread distribution. We generated sequences for five nuclear markers which were used in the global typhlopoid phylogeny and built phylogenetic trees of the superfamily Typhlopoidea. We also carried out divergence time analysis and biogeographic analysis to understand the time and modes of dispersal and diversification of these species. The results show Indotyphlops sensu lato to be polyphyletic, with the clade consisting of I. porrectus and I. exiguus sister to a clade consisting of the southeast Asian typhlopid genera Ramphotyphlops, Anilios, Malayotyphlops, Acutotyphlops, Sundatyphlops, and Indotyphlops sensu stricto. The other clade consists of I. pammeces and I. braminus from the Indian subcontinent and I. albiceps from Southeast Asia. Biogeographical analysis suggests two dispersals from Asia to the Indian landmass-an earlier dispersal from Eurasia into India led to the lineage consisting of I. porrectus and I. exiguus, followed by a later dispersal that evolved into I. pammeces and I. braminus. These results necessitate a taxonomic revision. We propose the genus Pseudoindotyphlops gen. nov. for the clade currently consisting of the most recent common ancestor (MRCA) of I. porrectus and I. exiguus, and all descendants thereof.

Myostatin is a known negative regulator of muscle tissue growth. Thus, an inhibitor of myostatin may be therapeutically useful as an anabolic agent for the muscle tissue. A promising gene-silencing approach for gene therapy is DNA interference (DNAi), a sequence that is complementary to the promoter region of a target gene. To confer resistance to nuclease digestion, several modifications such as methylphosphonate or phosphorothioate have been proposed, wherein a nonbridging oxygen atom in the oligonucleotide phosphate backbone is replaced by sulphur. The aim of the present study was to assess the effectiveness of the DNAi molecule with phosphorothioate (PS) and without phosphorothioate (WPS) modification for inhibition of myostatin gene expression in mice. Eighteen four-week-old male BALB/c mice were randomly divided into three groups: DNAi-PS (n = 6), DNAi-WPS (n = 6) and control (n = 6). Intraperitoneal injections of DNAi (10 mg/kg) were given once a week, and mice body weights were measured weekly and sacrificed after three weeks. The expression of myostatin was assessed using real-time quantitative polymerace chain reaction. For histological evaluation, the skeletal muscle tissue was dissected from the biceps. The results were analysed by a t-test. Results demonstrated that administration of DNAi intraperitoneally with modification could suppress myostatin expression by up to 70%. Leg weight and histological analysis proved that chemically modified DNAi significantly suppressed the myostatin gene in mice. Overall, the results on DNA-induced gene silencing by antisense DNA oligonucleotides in animals can provide insight into the treatment of inherited diseases.

Colorectal cancer (CRC) is known to develop due to the accumulation of both genetic and epigenetic alterations, resulting in the conversion of intestinal epithelial cells to malignant adenocarcinoma cells. Caudal type homeobox 1 (CDX1) gene is a homeobox transcription factor and a selective tumour suppressor gene that is an important factor for the development of intestinal cells. This gene plays a role in the differentiation of intestinal epithelial cells, and its expression decreases in a number of cell lines derived from CRC, which suggests that a lack of CDX1 expression is a risk factor for the development of colorectal carcinoma. Therefore, the methylated DNA amounts of CDX1 gene in stool samples were investigated as a noninvasive method for the detection of CRC. In the present study, the methylation of CDX1 gene promoter region was assessed in stool samples of 50 CRC patients and 50 healthy individuals by MethyLight PCR using two primers and a Taq Man probe, which was completely specifically designed for fully methylated DNA of the gene promoter region. The percentage of methylated reference (PMR) of the studied gene in all samples was calculated similarly to previous studies. Statistical analysis was performed using SPSS 16. The PMR medians were 3.25 (95% CI: 0.1-100) and 0.1 (95% CI: 0.07-1) in the stool samples of CRC patients and healthy individuals, respectively. The results showed a significant difference in CDX1 gene PMR between stool samples of CRC patients and controls (P-value0.001). According to the results of this study, it can be argued that measurement of CDX1 gene DNA in stool samples using the MethyLight PCR has acceptable sensitivity and specificity, and is adequately potential to be used as a noninvasive complementary method for the diagnosis of CRC, along with colonoscopy as the gold standard to this end. This study is the first report on CDX1 methylation in stool samples of CRC patients. Therefore, further research should be carried out with a larger sample size to evaluate its efficacy as a diagnostic biomarker in clinical laboratories.

Raising Iraqi indigenous chickens (IIC) is restricted by their thin and low eggshell weights. Due to the importance of the prolactin (Prl) gene in regulating a wide range of egg production traits, this study assessed the potential genetic polymorphisms associated with Prl that may influence these traits. The polymorphism was examined in three Prl loci of the IIC breed (n = 120) in comparison with the standard Hyline breed (n = 120). The polymorphism of both breeds was associated with eggshell weight and thickness indices for 16 weeks, starting from the 44th to the 59th week. After genotyping three loci within Prl by polymerase chain reaction-single-stranded conformation polymorphism (SSCP) method, only one novel SNP was identified in intron 4, namely 129G>A. The identified intron SNP exerted a significant association with both eggshell thickness and weight indices throughout the investigation period. Birds with GG genotype exhibited higher indices of eggshell thickness and weight than those with the GA and AA genotypes, respectively. The employed in silico tools predicted a remarkable ability for the identified SNP to alter the mRNA splicing pattern, which might be related to altered prolactin activity in birds having an alternative allele A. This study is the first to suggest the significance of this novel intron SNP in assessing eggshell traits in chickens.

We report the case of a Spanish pediatric patient with developmental delay, hypotonia, feeding difficulties, visual problems, and hyperkinetic movements. Whole-exome sequencing uncovered a new heterozygous de novo Synaptotagmin 1 (SYT1) missense variant, NM_005639.3:c.930T>A (p.Asp310Glu), in a female proband. This gene encodes the synaptotagmin-1 (SYT1) protein, which is a component of a protein complex involved in the fusion of synaptic vesicles with the presynaptic membrane. Pathogenic SYT1 variants have been associated with Baker-Gordon syndrome (BAGOS), an autosomal dominant neurodevelopmental disorder. Although up to 30 cases have been identified worldwide, to the best of our knowledge, this is the first patient described with mitochondrial respiratory chain deficiencies and rod-cone dysfunction. In conclusion, our data expand both the genetic and phenotypic spectrum associated with SYT1 variants.

A recent report by G. Clark points to a sustained persistence of social status in England that extends vertically across several generations and horizontally across many levels of kinship. We seek to put his findings in historical perspective. We do so by relating them to two lines of thinking related to biological inheritance. One predated the rediscovery of Mendel's work and led to the field of quantitative genetics, which dealt on the whole with quasi-continuously varying traits. The other is based on the rediscovery itself and led to a reconciliation between quantitative genetics and discrete Mendelian elements of heredity. Both were enmeshed with the supposed need for, and societal consequences of, eugenics and assortative mating. Also on both issues, the significant ideas can be traced to R. A. Fisher, inspired in one case by F. Galton and in the other by J. A. Cobb, with strong support for Galton and Cobb coming from Karl Pearson. Clark's findings point to societal stratification, and assortative mating for wealth is a straightforward hypothesis to account for it. However, it should be noted that the findings support, but do not prove, the hypothesis.

Phenotypic mutants are valuable resources for elucidating the function of genes responsible for their expression. This study examined mutant rice strains expressing three traits: spotted leaf 6 (spl6), lax panicle (lax), and liguleless (lg). In the mutant, the spl6 phenotype was a genetically programmed lesion-mimicking mutation (LMM) that displayed spontaneously scattered spots across the leaf surface. In the lg trait, the plant lacked a collar region, and there were no auricles and ligules at the junction of the leaf blade and leaf sheath. The lax panicle trait manifested as sparely arranged spikelets resulting from the terminal spikelet with no lateral spikelets, which caused a drastic reduction of the total seed number in the mutant. All three mutant genes were genetically recessive and had nuclear gene regulation. The dihybrid segregation of the lg gene was classified independently according to the Mendelian 9:3:3:1 dihybrid segregation ratio in the F₂ generation, suggesting that the lg gene is not linked to the same chromosome as the lax and spl6 genes. On the other hand, spl6 and lax were not assorted independently, indicating that they are closely linked on chromosome 1 in rice. Additional linkage analysis from the recombination of spl6 and lax genes reconfirmed that the two genes were ~9.4 cM away from each other. The individual single-gene mutant plant from one plant with a three-gene mutation (spl6, lax, and lg) was isolated and characterized, which will be a crucial resource for the gene cloning and molecular characterization of these genes.