Journal of Applied Genetics最新文献

Perrault syndrome (PS) is an extremely rare autosomal recessive condition characterized primarily by bilateral sensorineural hearing loss in both genders and primary or secondary ovarian failure in females. Neurological features such as cerebral ataxia, peripheral neuropathy, epilepsy, and intellectual disability are frequent manifestations of PS. To date, six genes have been reported to cause PS, and nearly 100 families have been identified worldwide with this syndrome. Exome sequencing was performed on two unrelated Iranian families presenting with Perrault syndrome. Family A included three offspring affected with bilateral severe to profound congenital hearing loss, cerebral ataxia, epilepsy, and intellectual disability. Family B included a female affected with bilateral moderate to severe hearing loss and peripheral neuropathy. In Family A, a compound heterozygous mutation (c.21delA and a novel missense mutation c.512C > G) in the CLPP gene was identified. In Family B, a homozygous mutation c.874C > A in the TWNK gene was found in the affected female. These findings represent the first report of genetic variations in the CLPP and TWNK genes in Iranian families with Perrault syndrome. The study expands the genetic landscape of Perrault syndrome by identifying novel mutations in the CLPP and TWNK genes. It also highlights the utility of exome sequencing as a cost-effective and powerful tool for diagnosing rare and complex genetic disorders like Perrault syndrome.

Bread wheat (Triticum aestivum L.) is one of the widely consumed staple foods, providing 20% of the total protein and calories in human nutrition. Seeing its importance in the global food supply, the enrichment of functional genomic resources is vital for meeting future demands and ensuring sustainable production. In addition to the presence of functional domains, the presence of microsatellites within transcription factors makes them valuable candidates for enriching functional marker resources. The NAC transcription factor family regulates a variety of physiological processes in cereal crops. Hence, the present study aims to develop and characterize Triticum aestivum NAC MicroSatellites (TaNACMS) to enrich functional marker resources for genetic diversity analysis, marker-assisted selection, and evolutionary studies. In total, 520 SSRs were identified from 451 TaNAC sequences, and a set of 66 TaNACMS was used for cross-transferability in wild/related wheat species. The cross-transferability rate of 90.22% revealed high locus conservation. Further, 16 TaNACMS were utilized for the characterization of genetic diversity in Indian wheat varieties. These TaNACMS produced 40 alleles (2.5 alleles per locus) with an average observed heterozygosity (H_o), expected heterozygosity (H_e), and polymorphic information content (PIC) of 0.392, 0.417, and 0.380, respectively. The genetic analysis of wheat genotypes, using principal coordinates analysis (PCoA), neighbor-joining (NJ) clustering, and Bayesian-based STRUCTURE, has revealed three distinct genetic clusters. Two of these clusters consist of Indian wheat varieties, while the third cluster comprises wild/related wheat species. In conclusion, the high rate of transferability of TaNACMS can be effectively utilized for gene flow both within and between species, highlighting evolutionary connections between cultivated wheat and related species. Additionally, these SSRs will aid the marker repository and benefit the wheat improvement programs through marker-assisted selection (MAS).

Alternative splicing (AS) produces various forms of mRNAs and protein isoforms and contributes to biodiversity. However, different mRNAs might have identical CDS and encode the same protein sequence. It is unclear why organisms need these distinct mRNAs if they encode the same protein? We propose two complementary hypotheses, namely adaptive hypothesis and error hypothesis, and tested these ideas using genomes of four representative organisms, human, mouse, fruitfly, and Arabidopsis. We found that only the fruitfly meets most predictions made by the adaptive hypothesis, while the other species generally align with the error hypothesis. Fruitfly exhibits a surprisingly high fraction (> 70%) of protein-coding genes (PCGs) having multiple mRNAs encoding identical proteins. These mRNAs have long CDS, variable UTR lengths, and highly conserved protein sequences. In contrast, opposite or insignificant trends are observed in human, mouse, and Arabidopsis. While molecular errors are common in cell systems, in species like the fruitfly with large effective population size, the strong natural selection might maintain those mRNAs with potentially adaptive regulatory roles. Although encoding identical proteins, different mRNAs can be regulated in a condition-specific manner, facilitating adaptive evolution. Our work provides novel perspectives in genomics and evolutionary biology.

The genetic structure and variability of sea trout populations in the southern Baltic Sea were shaped during the last glaciation, in parallel with the evolution of the Baltic Sea. However, human activities-particularly hydrotechnical development and the introduction of non-local genetic lines-have altered and partially reduced the original genetic diversity. In the present study, the authors describe the historical changes that have occurred and present the current level of genetic variability within Polish sea trout populations. A total of 575 sea trout from nine river populations and three hatchery broodstocks were genotyped at 13 microsatellite loci. The global F_ST obtained via AMOVA was moderate, at 0.041. The highest pairwise F_ST values were observed between the Rutki and Aquamar broodstocks and all other populations. The lowest and statistically non-significant pairwise differences were detected between the Rega and Ina river populations, as well as between the Słupia and Łupawa. Genetic structure analysis revealed geographic differentiation, identifying either four or seven distinct clusters. Additionally, neighbour-joining clustering showed that the examined populations and stocks were divided into two main subgroups: one consisting of samples related to the Vistula origin, and the other comprising clearly separated Pomeranian populations. This paper discusses the emergence of new genetic variability driven by microevolutionary processes and presents a revised approach for sea trout population management.

Given the importance of epigenetic mechanisms in the downregulation of tumor suppressor genes and the activation of oncogenes, herein we focused on microRNA silencing as a cause of oncogene activation in laryngeal squamous cell carcinoma (LSCC). In our study, we aimed at identifying regulatory microRNA signatures in LSCC mRNA profiles from our previous analysis. By this approach, we identified 14 overexpressed genes that shared a common regulatory hsa-miR-299-5p signature in LSCC samples. Subsequent RT-qPCR analysis confirmed the downregulation of hsa-miR-299-5p as well as the overexpression of 3 out of 14 genes: PATZ1, PURB, and TFAM in both LSCC cell lines and tumor samples compared to non-cancerous controls. Further, we have demonstrated a direct interaction between hsa-miR-299-5p and TFAM 3'UTR using dual luciferase assay. Importantly, we have shown decreased TFAM protein level after mimicry of hsa-miR-299-5p expression in three LSCC cell lines. Moreover, cell lines with restored activity of hsa-miR-299-5p demonstrated reduced viability compared to cell lines treated with the negative control. In conclusion, we point to hsa-miR-299-5p as a tumor-suppressive microRNA with the potential to regulate TFAM and consequently influence cell viability.

Winter oilseed rape (Brassica napus), a crucial crop in temperate regions, is a key contributor to global vegetable oil production and an essential component of crop rotations due to its ability to improve soil structure and fertility. Enhancing its yield is vital for meeting the increasing demand for sustainable oil production, supporting food security, and optimizing biofuel production, while also ensuring the economic viability of agricultural systems in colder climates. The aim of the research was to determine association between SNP molecular markers and rapeseed yield. The plant material for this study consisted of 276 oilseed rape hybrids. The experiment was conducted in four localities: Borowo, Kończewice, Małyszyn, and Strzelce. The mean yield values ranged from 0.07 kg (for hybrid EH_20212 in Małyszyn) to 9.10 kg (for hybrid EH_20410 in Kończewice). The genotype matrix for 276 hybrids was constructed using marker data from the parental genotypes of inbred individuals (maternal and paternal lines). The matrix was coded as {- 1, 0, 1}, assuming an additive effect of the alleles. A total of 13,116 SNP markers were identified. For association mapping, 12,581 polymorphic markers were used. The results of the observation of the yield and sequencing were used for association mapping, which ultimately resulted in the selection of twenty-six molecular markers important (LOD > 5.0) simultaneously in all four localities.

High plant density assumes significance for higher yield per unit area. However, reports on breeding for ideal plant architecture (IPA) in maize are limited due to lack of comprehensive characterization of germplasm. Here, we assessed genetic variation and identified inbreds for 14 plant architectural traits among 48 subtropical maize inbreds through multi-location analysis. Wide genetic variation for (i) stalk-related traits, viz., plant height (100.5-209.8 cm), ear height (26.4-106.3 cm), internode number (3.8-10.9), and internode length (8.1-15 cm); (ii) leaf-related traits, viz., leaf length (39.7-77.1 cm), leaf width (5.2-10.5 cm), leaf area (158.6-568.4 cm²), leaf angle (18.4-84.6°), leaf orientation value (2.2-71.3), number of leaves above-ear (3.2-7.2), and husk number (5.7-14.4); and (iii) tassel-related traits, viz., tassel height (21.8-34.9 cm), number of tassel branches (3.9-16.6), and tassel branching angle (10.2-78.4°) were observed. All traits showed significant variation due to environment and genotype × environment interactions. Correlation analysis implied that narrow leaf angle would produce compact tassel as well (r = 0.53, p < 0.001). Internode number and leaf width (r = - 0.33, p = 0.031), number of leaves and leaf length (r = 0.42, p = 0.004), plant height and leaf length (r = 0.39, p = 0.005), and leaf length and tassel height (r = 0.44, p = 0.003) were also associated. HKI-1105, CML-568, BAUIM-4, and BAUIM-2 were the most stable and promising inbreds with IPA using three popular selection indices (AMMI-TGSI, WAASBY-I, and MTSI). These promising inbreds could serve as suitable donors for germplasm diversification, besides generating hybrid combinations for high plant density. This is the first comprehensive analysis to characterize sub-tropically adapted maize inbreds for plant architectural traits.

Essential thrombocythemia and primary myelofibrosis belong to the group of BCR::ABL1-negative myeloproliferative neoplasms. The presence of mutations in the JAK2, CALR, and MPL genes is essential for the diagnosis of myeloproliferative neoplasms. These mutations are called "driver" mutations. However, not only leading mutations have been identified in patients with MPN, but also more than half of individuals with essential thrombocythemia and more than 80% of patients with myelofibrosis have additional mutations. One technique that makes it possible to find prognostic, predictive, and diagnostic indicators is next-generation sequencing. Coexisting mutations are associated with reduced response to therapy, shortened overall survival, and a higher risk of transformation to acute myeloid leukemia or myelofibrosis. The study group consisted of 42 patients with the diagnosis of BCR::ABL1-negative MPN and the presence of a mutation in the CALR gene. The research material was archival, and DNA was obtained from patients' peripheral blood. Forty genes (17 genes, 23 hotspots) were sequenced using the commercial kit AmpliSeq for Illumina Myeloid Panel applying the targeted next-generation sequencing approach. For the study, the Illumina MiniSeq platform was used. The analysis of the obtained genetic results was carried out using bioinformatics tools and genetic databases. We studied 42 CALR-positive ET (n = 28) and MF (n = 14) patients with NGS panel testing. The median age at diagnosis of the entire patient series was 58 years. Additional mutations were detected in 48% of patients in the whole cohort. The most frequently mutated genes in the study population were ASXL1, TET2, and DNMT3A, which are largely associated with epigenetic regulatory mechanisms. NGS panel studies represent a breakthrough in the diagnostic and prognostic evaluation of MPNs with CALR mutations. The ability to perform such a comprehensive study provides valuable information on the biology of the disease and the selection of the appropriate treatment regimen. The use of new technologies shows that not only driver mutations have clinical significance for the patient. NGS has the potential to increase the precision and effectiveness of diagnosis and prognosis.