Journal of Genetics最新文献

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.

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, wholegenome 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.

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.

Kruppel-like factor 1 (KLF1) is an essential erythroid-specific transcription factor. Several reports have shown that KLF1 gene mutations are associated with increased levels of Hb F and Hb A₂. However, scarce population studies have analysed common KLF1 variations. This study examines the potential association with Hb F and Hb A₂ levels in β-thalassemia (β-thal) carriers of Portugueseancestry of the four common KLF1 gene variants: -251C>G (rs3817621) and -148G>A (rs79334031), in the promoter region; and c.115A>C (p.Met39Leu) (rs112631212) and c.304T>C (p.Ser102Pro) (rs2072597), in exon 2. Ninety-two Portuguese β-thal carriers (43 males and 49 females) aged 2 to 77 years old (mean 32.55 years) were engaged in the study. Hb F levels range from 0.2 to 12.5% and Hb A₂ was above the normal level, ranging from 3.6 to 6%. The Hb A₂ and Hb F levels were determined by high-performance liquid chromatography. Single-nucleotide polymorphisms were genotyped by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Minor allele frequencies for SNPs rs3817621 (G), rs79334031 (A), rs112631212 (C) and rs2072597 (C) were 0.196, 0.016, 0.011 and 0.169, respectively. Basic simple linear regression in the total population showed no significant associations with the levels of Hb F (P>0.05). For the low-frequency variant -148A, a statistically significant association was found with increased levels of Hb A₂ (β = 0.855; P = 0.017). In conclusion, an association signal with Hb A₂ levels was observed for the variant -148A>G (rs79334031). The complex pattern of SNP interactions related to their influence on the KLF1 transcriptional activity mayexplain the absence of association with Hb F levels.

A significant proportion of next-generation sequencing (NGS) data ends up not being used since they comprise information out-of-scope of the primary studies. This 'waste' of potential can be harnessed to explore organellar genomes, such as the mitochondrial DNA, and be used for evolutionary, conservation and biodiversity research. We present the complete mitochondrial genomes of the deep-sea methanotrophic sponges Hymedesmia methanophila and Iophon methanophila (Demospongiae, Poecilosclerida) retrieved from previously published whole metagenome sequencing data. The predicted mitogenome of H. methanophila (18,657 bp) and I. methanophila (18,718 bp) present the characteristic arrangement observed among Poecilosclerida sponges. These mtDNAs encode the usual set of 14 proteins, two ribosomal RNA, and 24 or 23 transfer RNA genes, respectively, with intergenic regions amounting ~5% of their total length. The overall similarity of these mitogenomes to those of phylogenetic relatives, both in organization and divergence, suggests that neither their extremophilic habitat in asphalt seeps within the deep sea nor their symbiotic association with methaneoxidizing bacteria imposed a major influence on the evolution of their mitochondrial genome. This research shows how metagenomic data can be leveraged to extract additional genetic knowledge from primary metagenome sources, and by exploiting previously unexplored sequencing data, valuable information can be unlocked to shed light on the evolutionary dynamics of diverse organisms inhabiting extreme environments.

The most severe type of male infertility is nonobstructive azoospermia (NOA), where there is no sperm in the ejaculate due to failure of spermatogenesis. The predictable frequency of NOA in the general population is one in 100 men. Genetic studies have recognized dozens of NOA genes. Most NOA aetiologies remain idiopathic. Monogenic mutations can be a reason for a part of idiopathic NOA cases. To address this, we studied the pedigree of a consanguineous family with three NOAs by a family-based exome sequencing. Our goal was to pinpoint the genetic variants responsible for idiopathic NOA to aid future clinical genetic diagnostics and treatment strategies. Bioinformatics analysis followed by Sanger sequencing revealed that NOA patients were homozygous for a rare novel missense variant in PNLDC1(NM_173516:exon9:c.710G>A;p.Gly237Asp). In silico, single-cell RNA sequencing data analysis and protein modelling demonstrated that PNLDC1, Gly237Asp resided in the conserved region of the CAF1 domain which could lead to local instability in the structure and alteration of protein phosphorylation site. We conclude that the novel missense PNLDC1 variant may affect meiosis and spermatogenesis, leading to NOA and the genetic cause of this idiopathic NOA family. Our result helps genetic counselling for idiopathic NOA cases and provides the occasion for more efficient diagnosis in the clinical setting.

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.

Upregulation of homeoprotein SIX1 in gastric cancer (GC) is related to tumour proliferation and invasion. MicroRNA-7160 (miR-7160) is a homeoprotein SIX1-targeting miRNA that downregulates miR-7160, leading to cancer development. Total gastric cancer samples were collected from six patients, and relative expression levels of SIX1 mRNA and miRNAs were analysed by qRT-PCR. To evaluate the regulation of SIX1 by miR-7160, pGL3-SIX1-mut, pGL3-SIX1, and miR-7160 mimics transfected into cells using lipofectamine 2000. After transfection, proliferation and apoptosis in cultured cells were assessed using the nuclear TUNEL staining and CCK8 reagent, respectively. We demonstrated that the downregulation of miR-7160 in human gastric cancer cells is related to the upregulation of SIX1 mRNA. In gastric cancer cell lines, miR-7160 overexpression could downregulate the expression and inhibit cancer cell proliferation and growth in vitro. However, overexpression of miR-7160 did not increase gastric cancer cell apoptosis. In vitro downregulation of SIX1 decreased vimentin, N-cadherin, and other EMT-related gene expression and increased E-cadherin expression. In brief, miR-7160, by targeting SIX1, inhibits gastric cancer proliferation and cell growth in vitro, which provides an idea for introducing a new treatment option for gastric cancer.

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.

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.