Journal of Genetics最新文献

Intellectual developmental disorder, X-linked 104 (XLID104), caused by the FRMPD4 gene variant, is a rare X-linked genetic disease that primarily manifests as intellectual disability (ID) and language delay, and may be accompanied by behavioural abnormalities. Currently, only 11 patients from four families have been reported to carry FRMPD4 gene variants. Here, we report a rare case of a Chinese patient with XLID104 who was presented with severe ID and language impairment. Genetic testing results showed that the patient had a novel hemizygous variant on FRMPD4 inherited from the heterozygous variant NM_001368397: c.1772A>C (p.Glu591Ala) carried by his mother. To our knowledge, this variant has not been reported previously. Western blot results for the recombinant plasmid constructed in vitro indicated that the expression of the mutant protein may be reduced. Using molecular dynamics simulations, we predicted that the mutant protein may affect the interaction of the FRMPD4 protein with DLG4. In this study, we expand the spectrum of FRMPD4 variants and suggest that the clinical awareness of the genetic diagnosis of nonsyndromic ID should be strengthened.

The aroma in rice is the most appreciable quality trait, controlled by the loss of function of the betaine aldehyde dehydrogenase 2 (BADH2) gene. In the present study, indica rice cultivars (basmati, nonbasmati aromatic, and nonaromatic) were screened to explore allelic differences in the BADH2 gene using two functional markers (badh2-p-5′UTR and FMbadh2-E7). Notably, the results of the present mutational analysis showed that both markers confirmed a different mutation in indica rice cultivars than earlier reported japonica accessions. It was found that there is 250-bp deletion in the promoter region of aromatic Kagesali and Kalakrishna as compared to nonaromatic Kolamb. The results of FMbadh2-E7 showed 8-bp deletion and six SNPs in exon 7 of the Kalakrishna cultivar. Interestingly, the nonbasmati aromatic Lalbhat rice cultivar did not harbour any reported mutation and showed a novel BADH2 allele carrying 1-bp deletion in exon 7. Among the selected aromatic rice cultivars, eight cultivars showed mutation in the 5′ UTR region and interestingly 23 rice cultivars carried the mutation in both 5′ UTR and exon 7 of a BADH2 gene. The 2-acetyl-1-pyrroline (2AP) biosynthesis related metabolites, enzyme assay and gene expression supported mutation in BADH2 gene and expression of 2AP in aromatic rice cultivars under study.

Typhoid is endemic in India and has high global incidence. There were large outbreaks of typhoid in India between 1990 and 2018. Available typhoid vaccines induce variable levels of protective antibodies among recipients; thus, there is variability in response to the vaccine. Interindividual genomic differences is hypothesized to be a determinant of the variability in response. We studied the antibody response of ~1000 recipients of the Vi-polysaccharide typhoid vaccine from Kolkata, India, who showed considerable variability of antibody response, i.e., anti-Vi-polysaccharide antibody level 28 days postvaccination relative to prevaccination. For each vaccinee, whole-genome genotyping was performed using the Infinium Global Screening Array (Illumina). We identified 39 SNPs that mapped to 13 chromosomal regions to be associated with antibody response to the vaccine; these included SNPs on genes LRRC28 (15q26.3), RGS7 (1q43), PTPRD (9p23), CERKL (2q31.3), DGKB (7p21.2), and TCF4 (18q21.2). Many of these loci are known to be associated with various blood cell traits, autoimmune traits and responses to other vaccines; these genes are involved in immune related functions, including TLR response, JAK–STAT signalling, phagocytosis and immune homeostasis.

Rainbow trout (Oncorhynchus mykiss) and brown trout (Salmo trutta fario) are popular salmonid species that are reared for sport and recreational activities worldwide. In India, they were introduced and successfully established in the late 19th and early 20th centuries by the European settlers. However, until now, no studies have analysed the genetic integrity of wild trout populations in India. Therefore, this study aimed to analyse the genetic integrity of the wild rainbow trout populations from south India, one wild rainbow trout population from north India, and one wild brown trout population from north India. Genetic diversity studies revealed low genetic diversity in all the population with genetic bottlenecks in two trout populations from south India and disruption of alleles in the populations from north India. The results showed that the south Indian trout populations are in a comparatively poor condition than the north Indian trout populations, and stocking efforts have recently been carried out to enhance the genetic diversity of south Indian trout populations.

MOCA1 encodes the last key glucuronosyltransferase for ionic stress sensor glycosyl inositol phosphoryl-ceramide (GIPCs) biosynthesis in Arabidopsis, which indicates that the MOCA gene family play important role in plant tolerance to salt stress. However, the isolation and function of MOCAs in staple crops have not been reported and the downstream targets of MOCAs in salt stress tolerance signalling pathway are not clear. In this study, we identified 110 MOCA genes in wheat which were classified into five clades and they differed in gene structure, protein length, conserved motifs and expression profiles in different tissues and under salt stress. TaMOCA1 was selected for further functional study in response to salt stress. TaMOCA1 was rapidly induced by NaCl treatment. The 35S::TaMOCA1-GFP construction showed the cell nucleus and cytoplasm location in wheat protoplast. TaMOCA1 over-expressing Arabidopsis seedlings formed longer primary roots and more lateral roots than the wild type ones under 50 mM NaCl treatment. The over-expressing Arabidopsis had higher expression levels of HKT1, but lower expression levels of NHX1 and SOS genes than the wild type. Also, the transgenic plants had higher SOD activity and lower MDA content than the wild Arabidopsis seedling under salt stress. These results may indicate that TaMOCA1 increases salt stress tolerance through decreasing Na⁺ loading from the xylem parenchyma cells to the xylem via SOS1 and HKT1, hence lowering root-to-shoot delivery of Na⁺ and superior antioxidant ability. All these results lay a foundation for further functional study of MOCAs in wheat.

Abstract

Saccharomyces cerevisiae has been demonstrated to be an excellent platform for the multi-fragment assembly of large DNA constructs through its powerful homologous recombination ability. These assemblies have invariably used the stable centromeric single copy vectors. However, many applications of these assembled genomes would benefit from assembly in a higher copy number vector for improved downstream extraction of intact genomes from the yeast. A review of the literature revealed that large multi-fragment assemblies did not appear to have been attempted in multicopy vectors. Therefore, we devised a toolkit that would enable one to seamlessly transition with the same assembling fragments between a single copy and a multicopy vector. We evaluated the assembly of a 28 kb attenuated SARS-CoV-2 genome (lacking the N gene) from 10 fragments in both single copy and multicopy vector systems. Our results reveal that assembly was comparably efficient in the two vector systems. The findings should add to the synthetic biology toolkit of S. cerevisiae and should enable researchers to utilize any of these vector systems depending on their downstream applications.

Abstract

Polycystic ovary syndrome (PCOS) is one of the most common endocrine diseases in women. In recent years, the effects of vitamin D receptor (VDR) gene variants and VitD3 levels on clinical features of PCOS have been frequently described. In this study, we aimed to determine the relationship between VDR ApaI, TaqI and Cdx2 gene variants and VitD3 levels in PCOS patients. Patients were divided into two groups: BMI<25 and BMI≥25. VDR genotypes were determined by real-time polymerase chain reaction (PCR) and serum VitD3 levels were examined by ELISA. We observed that frequencies of the Apa1 AC genotype, C allele and Cdx2 T allele are increased in the BMI≥25 group compared to BMI<25 group. Also, the ApaI C allele, Taq1 AA genotype and A allele, Cdx2 CC genotype and C allele are associated with increased triglyceride, total cholesterol, LDL-cholesterol levels in patients with BMI≥25. When examining the relationship between VitD3 levels and clinical profiles in all PCOS patients, regardless of BMI distinction, it is determined that there is a positive correlation between LDL-cholesterol and ftestosterone levels. The present findings suggest that VDR variants are one of the most important risk factors for PCOS, especially for patients with BMI≥25.

Dissecting the molecular basis of adaptation remains elusive despite our ability to sequence genomes and transcriptomes. At present, most genomic research on selection focusses on signatures of selective sweeps in patterns of heterozygosity. Other research has studied changes in patterns of gene expression in evolving populations but has not usually identified the genetic changes causing these shifts in expression. Here we attempt to go beyond these approaches by using machine learning tools to explore interactions between the genome, transcriptome, and life-history phenotypes in two groups of 10 experimentally evolved Drosophila populations subjected to selection for opposing life history patterns. Our findings indicate that genomic and transcriptomic data have comparable power for predicting phenotypic characters. Looking at the relationships between the genome and the transcriptome, we find that the expression of individual transcripts is influenced by many sites across the genome that are differentiated between the two types of populations. We find that single-nucleotide polymorphisms (SNPs), transposable elements, and indels are powerful predictors of gene expression. Collectively, our results suggest that the genomic architecture of adaptation is highly polygenic with extensive pleiotropy.

Abstract

This article aimed to detect the existence of barley-specific Nikita and Sukkula retrotransposons in domestic geese samples and to evaluate the evolutionary relationships between these and other transposons belonging to the family Anatidae. Inter-retrotransposon-amplified polymorphism-polymerase chain reaction (IRAP-PCR) method was performed for these retrotransposons movements in three diverse domestic goose populations (Chinese × Embden crossbred, Turkish White, and Turkish Multicolor). Polymorphism ratios were between 0 and 33% in all samples for Nikita and 0–73% in all samples for Sukkula. In addition, intrapopulation genetic polymorphism rates were also 0–15% in Chinese × Embden crossbred, 0–25% in Turkish White, 0–25% in Turkish Multicolor for Nikita; while 0–27% in Chinese × Embden, and 0–50% in Turkish Multicolor for Sukkula. There was no polymorphism for Sukkula among Turkish White samples. Moreover, the neighbour-joining method was used for phylogenetic tree construction using 38 sequences of different ducks, geese, and swans. In silico analyses supported the transitions of retrotransposons in the family Anatidae. It is concluded that transposon mobility among the phylogenetically distant species may lead to understanding evolutionary relationships. This report is one of the first studies investigating retrotransposon movements in domestic geese, revealing a new perspective on the goose genome regarding mobile genetic elements.

Absorptive hypercalciuria (AH) is a prevalent cause of kidney stones, and the adenylate cyclase 10 (ADCY10) gene is a rare causative gene of AH. This study aims to investigate the genotypic and phenotypic characteristics of patients with AH caused by ADCY10 gene mutations. Whole-exome sequencing and Sanger sequencing were performed on the probands and their family members, respectively. Clinical and genetic data of patients with AH caused by ADCY10 gene mutations were collected and analysed retrospectively from the present study and published literature. Two female patients (6 years old and 1 year old) with multiple bilateral kidney stones were found to have a heterozygous c.3304T>C mutation and a heterozygous c.1726C>T mutation in the ADCY10 gene. Urinary metabolite analysis revealed that urine calcium / creatinine ratios were 0.95 mmol/mmol and 1.61 mmol/mmol, respectively. Both patients underwent thiazide intake postoperatively, and upon reexamination, urine calcium decreased to within the normal range. A total of 61 patients with AH were reported from previous and present studies. The sex ratio was 7:5 for males to females, and the mean age of onset was 23.61±20.08 years. A total of 16 ADCY10 gene mutations were identified, including seven missense (43.75%), five splicing (31.25%), two frameshift (12.50%) and two nonsense mutations (12.50%). Only two cases were identified as homozygous mutations (c.1205_1206del), and the others were heterozygous mutations. In summary, we identified two novel ADCY10 gene candidate pathogenic variants in Chinese pediatric patients, which expands the mutational spectrum of the ADCY10 gene and provides a potential diagnostic and therapeutic target.