exon

The hyperplasia-carcinoma sequence is a stepwise tumourigenic programme towards endometrial cancer in which normal endometrial epithelium becomes neoplastic through non-atypical endometrial hyperplasia (NAEH) and atypical endometrial hyperplasia (AEH), under the influence of unopposed oestrogen. NAEH and AEH are known to exhibit polyclonal and monoclonal cell growth, respectively; yet, aside from focal PTEN protein loss, the genetic and epigenetic alterations that occur during the cellular transition remain largely unknown...

BACKGROUND: Cystic fibrosis (CF) is caused by deleterious variants in each CFTR gene. We investigated the utility of whole-gene CFTR sequencing when fewer than two pathogenic or likely pathogenic (P/LP) variants were detected by conventional testing (sequencing of exons and flanking introns) of CFTR. METHODS: Individuals with features of CF and a CF-diagnostic sweat chloride concentration with zero or one P/LP variants identified by conventional testing enrolled in the CF Mutation Analysis Program (MAP) underwent whole-gene CFTR sequencing...

Polyglutamine (polyQ) sequences undergo repeat-length dependent formation of disease-associated, amyloid-like cross-β core structures with kinetics and aggregate morphologies often influenced by the flanking sequences. In Huntington's disease (HD), the httNT segment on the polyQ's N-terminal flank enhances aggregation rates by changing amyloid nucleation from a homogeneous mechanism to a two-step, heterogeneous process requiring an ɑ-helix-rich oligomeric intermediate. A folded, helix-rich httNT tetrameric structure suggested to be this critical intermediate was recently reported...

Common variable immune deficiency (CVID) is a heterogenous group of disorders characterized by varying degrees of hypogammaglobulinemia, recurrent infections, and autoimmunity. Currently, pathogenic variants are identified in approximately 20-30% of CVID cases. Here we report a 3-generation family with autosomal dominant Common Variable Immunodeficiency (CVID) diagnosed in 9 affected individuals. Although primary immune deficiency panels and exome sequencing were non-diagnostic, whole genome sequencing revealed a novel, pathogenic c...

Skin color is an important trait that determines the cosmetic appearance and quality of fruits. In cucumber, the skin color ranges from white to brown in mature fruits. However, the genetic basis for this important trait remains unclear. We conducted a genome-wide association study of natural cucumber populations, along with map-based cloning techniques, on an F2 population resulting from a cross between Pepino (with yellow-brown fruit skin) and Zaoer-N (with creamy fruit skin). We identified CsMYB60 as a candidate gene responsible for skin coloration in mature cucumber fruits...

HLA-DQA1*02:32 differs from DQA1*02:01:01 by one nucleotide substitution in codon 210 in exon 4.

The novel HLA-C*15:274 allele, first described in a potential bone marrow donor from Brazil.

HLA-B*15:02:15 differs from HLA-B*15:02:01:01 by one nucleotide in exon 2.

Objective: To analyze the distribution characteristics of UGT1A1 mutant genes (including enhancers, promoters, and exons 1-5) and further explore the correlation between UGT1A1 genotype and clinical phenotypes in patients with inherited hyperunconjugated bilirubinemia. Methods: Patients diagnosed with hereditary hyperunconjugated bilirubinemia at Nanjing Second Hospital from June 2015 to December 2022 were retrospectively analyzed. The UGT1A1 gene was examined using Sanger sequencing in all patients. Complete blood count, liver function, and abdominal imaging examinations were performed...

BACKGROUND: Cornelia de Lange syndrome (CdLS) is a multisystem genetic disorder, and cases caused by variants in the structural maintenance of chromosomes protein 3 (SMC3) gene are uncommon. Here, we report two cases of CdLS associated with novel pathogenic variants in SMC3 from two Chinese families. METHODS: Clinical presentations of two patients with CdLS were evaluated, and specimens from the patients and other family members were collected for Trio-based whole-exome sequencing...

Grain size has an important effect on rice yield. Although several key genes that regulate seed size have been reported in rice, their molecular mechanisms remain unclear. In this study, a rice small grain size 2 ( sms2 ) mutant was identified, and MutMap resequencing analysis results showed that a 2 bp insertion in the second exon of the LOC_Os02g01590 gene resulted in a grain length and width lower than those of the wild-type Teqing (TQ). We found that SMS2 encoded vacuolar acid invertase, a novel allele of OsINV3 , which regulates grain size...

The most common form of hereditary spastic paraplegia (HSP), SPG4 is caused by single nucleotide variants and microrearrangements in the SPAST gene. The high percentage of multi-exonic deletions or duplications observed in SPG4 patients is predisposed by the presence of a high frequency of Alu sequences in the gene sequence. In the present study, we analyzed DNA and RNA samples collected from patients with different microrearrangements in SPAST to map gene breakpoints and evaluate the mutation mechanism. The study group consisted of 69 individuals, including 50 SPG4 patients and 19 healthy relatives from 18 families...

Non-small-cell lung cancer (NSCLC) is the most prevalent type of lung cancer, with extensively characterized mutational spectra. Several biomarkers (such as EGFR , BRAF , KRAS gene mutations, etc.) have emerged as predictive and prognostic markers for NSCLC. Unfortunately, the quality of the available tumor biopsy and/or cytology material is not always adequate to perform the necessary molecular testing, prompting the search for alternatives. Cell-free DNA (cfDNA) found in plasma is emerging as a highly promising avenue or a supplementary method for assessing the efficacy of cancer treatments...

BACKGROUND: Gene rearrangements affecting KMT2A are frequent in acute myeloid leukemia (AML) and are often associated with a poor prognosis. KMT2A gene fusions are often detected by chromosome banding analysis and confirmed by fluorescence in situ hybridization. However, small intragenic insertions, termed KMT2A partial tandem duplication (KMT2A-PTD), are particularly challenging to detect using standard molecular and cytogenetic approaches. METHODS: We have validated the use of a custom hybrid-capture-based next-generation sequencing (NGS) panel for comprehensive profiling of AML patients seen at our institution...

BACKGROUND: Current clinical diagnosis pathway for lysosomal storage disorders (LSDs) involves sequential biochemical enzymatic tests followed by DNA sequencing, which is iterative, has low diagnostic yield and is costly due to overlapping clinical presentations. Here, we describe a novel low-cost and high-throughput sequencing assay using single-molecule molecular inversion probes (smMIPs) to screen for causative single nucleotide variants (SNVs) and copy number variants (CNVs) in genes associated with 29 common LSDs in India...

BACKGROUND: While rabbits are used as models in skin irritation tests, the presence of irregular patches and thickening on the dorsal skin can affect precise evaluation. In this study, genes associated with patchiness or non-patchiness on the dorsal skin of New Zealand rabbits were investigated to identify potential regulators of the patchiness phenotype. RESULTS: The results showed that parameters associated with hair follicles (HFs), such as HF density, skin thickness, and HF depth, were augmented in rabbits with the patchiness phenotype relative to the non-patchiness phenotype...

Posttranscriptional maturation and export from the nucleus to the cytoplasm are essential steps in the normal processing of many cellular RNAs. The RNA helicase UAP56 (U2AF associated protein 56; also known as DDX39B) has emerged as a critical player in facilitating and co-transcriptionally linking these steps. Originally identified as a helicase involved in pre-mRNA splicing, UAP56 has been shown to facilitate formation of the A complex during spliceosome assembly. Additionally, it has been found to be critical for interactions between components of the exon junction and transcription and export complexes to promote the loading of export receptors...

During the storage irreversible changes occur in eggs that result in a deterioration of their quality. The most significant changes affect the albumen. One of the major proteins of albumen present in egg white is lysozyme, which protects the embryo from microorganisms. This enzyme also contributes to the qualitative characteristics of albumen. It is possible that its polymorphism also affects the quality and stability of the obtained raw material that is, table eggs. Therefore, the aim of this study was to assess the potential effect of polymorphism in the lysozyme gene and protein on the quality changes during the storage of eggs derived from 2 genetic strains of Japanese quail belonging to various utility types...

BACKGROUND: The lack of stable-high yielding and direct-seeded adapted varieties with better germination ability from deeper soil depth and availability of molecular markers are major limitation in achieving the maximum yield potential of rice under water and resource limited conditions. Development of high-throughput and trait-linked markers are of great interest in genomics-assisted breeding. The aim of present study was to develop and validate novel KASP (Kompetitive Allele-Specific PCR) markers associated with traits improving germination and seedling vigor of deep sown direct seeded rice (DSR)...

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are characterized by nuclear depletion and cytoplasmic aggregation of TAR DNA-binding protein-43 (TDP-43). TDP-43 plays a key role in regulating the splicing of numerous genes, including TARDBP. This review aims to delineate two aspects of ALS/FTD pathogenesis associated with TDP-43 function. First, we provide novel mechanistic insights into the splicing of UNC13A, a TDP-43 target gene. Single nucleotide polymorphisms (SNPs) in UNC13A are the most common risk factors for ALS/FTD...