Alleles

Proteins carrying a signal peptide and/or a transmembrane domain enter the intracellular secretory pathway at the endoplasmic reticulum (ER) and are transported to the Golgi apparatus via COPII vesicles or tubules. SAR1 initiates COPII coat assembly by recruiting other coat proteins to the ER membrane. Mammalian genomes encode two SAR1 paralogs, SAR1A and SAR1B . While these paralogs exhibit ~90% amino acid sequence identity, it is unknown whether they perform distinct or overlapping functions in vivo. We now report that genetic inactivation of Sar1a in mice results in lethality during midembryogenesis...

Measuring inbreeding and its consequences on fitness is central for many areas in biology including human genetics and the conservation of endangered species. However, there is no consensus on the best method, neither for quantification of inbreeding itself nor for the model to estimate its effect on specific traits. We simulated traits based on simulated genomes from a large pedigree and empirical whole-genome sequences of human data from populations with various sizes and structures (from the 1,000 Genomes project)...

BACKGROUND: The Bangkaew dog is an indigenous dog breed in the Phitsanulok province of Thailand. This breed is recognized by the Fédération Cynologique Internationale (FCI), a global canine organization. The unique traits of the Bangkaew breed lead to purebred selection for breeding, while only their traits and pedigree from parental history are recorded. Determination of the risk of inbreeding depression and the origin of unknown DNA profiles is essential due to the challenges in predicting puppy characteristics, which are crucial for breed management and conservation...

Manganese is an important co-factor for numerous biological processes, including defense against reactive oxygen species. A common genetic variant in the manganese transporter SLC39A8 (p.Ala391Thr) has been associated with lower blood levels of manganese and with increases in markers of liver cell damage. Whether the variant confers an increased risk of liver disease is unclear. We tested the association of this variant with biochemical, imaging, and clinical hepatic traits and outcomes in large general population cohorts totaling up to one million individuals, including 991 cases with hepatocellular carcinoma (HCC) and 7,191 with cirrhosis...

This study aims to elucidate additional mutation loci associated with fluoroquinolone (FQ) resistance and evaluate the discriminatory capacity of mutation loci and allele mutation frequencies in identifying FQ-resistant Mycobacterium tuberculosis (MTB) isolates. A random selection of isolates was extracted from an ongoing collection. Drug resistance was determined using the resazurin microtiter assay (REMA) as the gold standard. Mutation loci and the burden of mutations in the quinolone resistance-determining region (QRDR) were elucidated through whole-genome sequencing (WGS)...

Pseudomonas aeruginosa is an opportunistic bacterial pathogen that commonly causes medical hardware, wound, and respiratory infections. Temperate filamentous Pf phages that infect P. aeruginosa impact numerous virulence phenotypes. Most work on Pf phages has focused on Pf4 and its host P. aeruginosa PAO1. Expanding from Pf4 and PAO1, this study explores diverse Pf phages infecting P. aeruginosa clinical isolates. We describe a simple technique targeting the Pf lysogeny maintenance gene, pflM ( PA0718 ), that enables the effective elimination of Pf prophages from diverse P...

Enhancers are critical for regulating tissue-specific gene expression, and genetic variants within enhancer regions have been suggested to contribute to various cancer-related processes, including therapeutic resistance. However, the precise mechanisms remain elusive. Using a well-defined drug-gene pair, we identified an enhancer region for dihydropyrimidine dehydrogenase (DPD, DPYD gene) expression that is relevant to the metabolism of the anti-cancer drug 5-fluorouracil (5-FU). Using reporter systems, CRISPR genome-edited cell models, and human liver specimens, we demonstrated in vitro and vivo that genotype status for the common germline variant (rs4294451; 27% global minor allele frequency) located within this novel enhancer controls DPYD transcription and alters resistance to 5-FU...

BACKGROUND: We report an obstetric case involving an RhD-positive woman who had developed a red blood cell (RBC) antibody that was not detected until after delivery of a newborn, who presented with a positive direct antiglobulin test result. Immunohematology studies suggested that the maternal antibody was directed against a low-prevalence antigen on the paternal and newborn RBCs. RESULTS: Comprehensive blood group profiling by targeted exome sequencing revealed a novel nonsynonymous single nucleotide variant (SNV) RHCE c...

BACKGROUND: Major bleeding occurs annually in 1%-3% of patients on vitamin K antagonists (VKAs), despite close monitoring. Genetic variants in proteins involved in VKA response may affect this risk. AIM: To determine the association of genetic variants (cytochrome P450 enzymes 2C9 [CYP2C9] and 4F2 [CYP4F2], gamma-glutamyl carboxylase [GGCX]) with major bleeding in VKA users, separately and combined, including vitamin K epoxide reductase complex subunit-1 (VKORC1)...

The novel HLA-A*30:218 allele, first described in a potential bone marrow donor from Brazil.

The HLA-A*24:627 allele differs from HLA-A*24:02:01:01 by one nucleotide substitution in codon 172 in exon 2.

HLA-DPA1*02:86 differs from HLA-DPA1*02:01:01 by a single nucleotide substitution at position 680 C > A in exon 4.

Compared with HLA-DRB1*09:01:02:05, the alleles HLA-DRB1*09:57 and HLA-DRB1*09:58 each show one nucleotide change, respectively.

HLA-A*31:01:53 differs from HLA-A*31:01:02:01 by one nucleotide change at nucleotide 900 in exon 5 from G to A.

The genetic architecture of mating-type loci in lichen-forming fungi has been characterized in very few taxa. Despite the limited data, and in contrast to all other major fungal lineages, arrangements that have both mating-type alleles in a single haploid genome have been hypothesized to be absent from the largest lineage of lichen-forming fungi, the Lecanoromycetes. We report the discovery of both mating-type alleles from the haploid genomes of three species within this group. Our results demonstrate that Lecanoromycetes are not an outlier among Ascomycetes...

Precision-cut lung slices (PCLS), ex vivo 3D lung tissue models, have been widely used for various applications in lung research. PCLS serve as an excellent intermediary between in vitro and in vivo models because they retain all resident cell types within their natural niche while preserving the extracellular matrix environment. This protocol describes the TReATS (TAT-Cre recombinase-mediated floxed allele modification in tissue slices) method that enables rapid and efficient gene modification in PCLS derived from adult floxed animals...

BACKGROUND AND OBJECTIVES: The intronic biallelic AAGGG expansion in the replication factor C subunit 1 ( RFC1 ) gene was recently associated with a phenotype combining cerebellar ataxia, neuropathy, and vestibular areflexia syndrome, as well as with late-onset ataxia. Following this discovery, studies in multiple populations extended the phenotypic and genotypic spectrum of this locus. Multiple benign and additional pathogenic configurations are currently known. Our main objectives were to study the prevalence of the pathogenic AAGGG expansion in the Cypriot population, to further characterize the RFC1 repeat locus allele distribution, and to search for possible novel repeat configurations...

Root architecture traits are belowground traits that harness moisture and nutrients from the soil and are equally important to above-ground traits in crop improvement. In soybean, the root length locus qRL16.1 was previously mapped on chromosome 16. The qRL16.1 has been characterized by transcriptome analysis of roots in near-isogenic lines (NILs), gene expression analysis in a pair of lines contrasting with alleles of qRL16.1 , and differential gene expression analysis in germplasm accessions contrasting with root length...

The CYP3A5*1 polymorphism, which increases the metabolic activity of CYP3A5, has been associated with a poor prognosis for asthma. In addition, individuals with this allele have a reduced response to corticosteroid treatment.

BACKGROUND: We assessed the potential role of serial circulating tumor DNA (ctDNA) as a biomarker to monitor treatment response to primary systemic therapy (PST) in breast cancer and evaluated the predictive value of ctDNA to further identify patients with residual disease. METHODS: We prospectively enrolled 208 plasma samples collected at three time points (before PST, after 2 cycles of treatment, before surgery) of 72 patients with stage Ⅱ-III breast cancer...