Результаты поиска

Mutant allele knockout with novel CRISPR nuclease promotes myelopoiesis in ELANE neutropenia.

Severe congenital neutropenia (SCN) is a life-threatening marrow failure disorder, usually caused by heterozygous mutations in ELANE. Potent … the heterozygous sites of single-nucleotide polymorphisms (SNPs) associated with most ELANE mutated alleles. In vitro studies demonstrate that patients' unedited hematopoietic CD34+ cells have significant abnormalities in differentiation and maturation, consistent with the hematopoietic defect in SCN patients. Selective knockout of the mutant ELANE allele …

The HLA-C*15:250 allele identified in a volunteer bone marrow donor.

HLA-C*15:250 differs from HLA-C*15:02:01:01 in codon 120 in exon 3.

Recognition of the HLA-C*07:1047 allele in a Russian bone marrow donor.

Complete genomic characterization of the HLA-C*07:1047 allele.

Bi-allelic variants in human TCTE1/DRC5 cause asthenospermia and male infertility.

Asthenozoospermia (AZS) is a common male infertility phenotype, accounting for 18% of infertile patients. The N-DRC (Nexin-dynein Regulatory Complex) complex is the motor regulating device in the flagellum, which is found in most eukaryotic organisms with flagellum. The deletion of TCTE1 (T-Complex-Associated Testis-Expressed 1), a component of the N-DRC complex also known as DRC5 (Dynein regulatory complex subunit 5), has been shown to cause asthenospermia in mice. This study mainly introduces a clinical case of male infertility with normal sperm count, normal morphological structure, but low

The lupus susceptibility allele DRB1*03:01 encodes a disease-driving epitope.

The HLA-DRB1*03:01 allele is a major genetic risk factor in systemic lupus erythematosus (SLE), but the mechanistic basis of the association is unclear. Here we show that in the presence of interferon gamma (IFN-γ), a short DRB1*03:01-encoded allelic epitope activates a characteristic lupus transcriptome in mouse and human macrophages. It also triggers a cascade of SLE-associated cellular aberrations, including endoplasmic reticulum stress, unfolded protein response, mitochondrial dysfunction, necroptotic cell death, and production of pro-inflammatory cytokines. Parenteral administration of IF

Major Histocompatibility Complex Class II HLA-DRB1 Allelic Epitopes in Fibromyalgia.

BACKGROUND: Preliminary evidence has pointed an association of the gene HLA-DRB1 with fibromyalgia. HLA-DRB1 alleles carrying the shared or susceptibility epitope encoding the five-amino acid motif QKRAA, QRRAA or RRRAA in positions 70 to 74 of the major histocompatibility complex class II DRβ chain are associated with several autoimmune diseases. OBJECTIVE: The objective of this study was to test the hypothesis that susceptibility epitope-encoding HLA-DRB1 alleles are associated with fibromyalgia. METHODS: Using a case-control design, the prevalence of susceptibility epitope-encoding HLADRB…

На основе последовательности частот HLA-DRB1, -DQB1 и -DPB1 в Гамбии.

Класс II HLA loci DRB1, DQB1 и DPB1 были напечатаны для в общей сложности 939 участников из Гамбии в разбивке по последовательности ампликонов. Участниками были представители нескольких регионов Гамбии, которые были взяты из двух исследований: семейного исследования, направленного на выявление связей между хост-генотипом и трахоматным шрамом (N = 796) и группового исследования, направленного на выявление корреляций иммунитета от трахомы (N = 143). Все лоси отошли от равновесия Харди-Вайнберга, вероятно, из-за семейного характера исследования: 608 участников включили по крайней мере еще одного

Совпадение в аннотации оригинала
Class II HLA loci DRB1, DQB1 and DPB1 were typed for a total of 939 Gambian participants by locus-specific amplicon sequencing. Participants … participants had at least one other family member included in the study population. The most common alleles for HLA-DRB1, DQB1 and DPB1 respectively were DRB1*13:04 (18.8 %), DQB1*03:19 (27.9 %) and DPB1*01:01 (25.4 %). Participants belonged to a variety of ethnicities, including the Mandinka, Fula, Wolof and Jola ethnic groups.

A loss-of-function IFNAR1 allele in Polynesia underlies severe viral diseases in homozygotes.

Globally, autosomal recessive IFNAR1 deficiency is a rare inborn error of immunity underlying susceptibility to live attenuated vaccine and wild-type viruses. We report seven children from five unrelated kindreds of western Polynesian ancestry who suffered from severe viral diseases. All the patients are homozygous for the same nonsense IFNAR1 variant (p.Glu386*). This allele encodes a truncated protein that is absent from the cell surface and is loss-of-function. The fibroblasts of the patients do not respond to type I IFNs (IFN-α2, IFN-ω, or IFN-β). Remarkably, this IFNAR1 variant has a mino

Melioidosis of the central nervous system; impact of the bimABm allele on patient presentation and outcome.

BACKGROUND: The autotransporter protein Burkholderia intracellular motility A (BimA) facilitates the entry of Burkholderia pseudomallei into the central nervous system (CNS) in mouse models of melioidosis. Its role in the pathogenesis of human cases of CNS melioidosis is incompletely defined. METHODS: Consecutive culture-confirmed cases of melioidosis at two sites in tropical Australia after 1989 were reviewed. Demographic, clinical and radiological data of the patients with CNS melioidosis were recorded. The bimA allele (bimABm or bimABp) of the B. pseudomallei isolated from each patient was

Variable and Severe Phenotypic Expression of the "Lebanese Allele" in Two Sisters with Familial Hypercholesterolemia.

The "Lebanese allele" {LDLR c.2043 C>A (p.cys681X)} is a nonsense mutation in the low-density lipoprotein receptor (LDLR) gene that results in a truncated non-functioning LDLR protein. We report two sisters of Lebanese descent who presented with familial hypercholesterolemia (FH) and were both heterozygous for the Lebanese allele, but had very distinct LDL-C levels and clinical phenotypes. Whereas one of the sisters had LDL-C in the expected range of Heterozygous FH (HeFH) with the Lebanese allele (LDL-C of 292 mg/dl), the other sister had a more severe LDL-C phenotype in the Homozygous FH (Ho

A missense allele of PEX5 is responsible for the defective import of PTS2 cargo proteins into peroxisomes.

Peroxisomes, single-membrane intracellular organelles, play an important role in various metabolic pathways. The translocation of proteins from the cytosol to peroxisomes depends on peroxisome import receptor proteins and defects in peroxisome transport result in a wide spectrum of peroxisomal disorders. Here, we report a large consanguineous family with autosomal recessive congenital cataracts and developmental defects. Genome-wide linkage analysis localized the critical interval to chromosome 12p with a maximum two-point LOD score of 4.2 (θ = 0). Next-generation exome sequencing identified a

Allele-specific editing ameliorates dominant retinitis pigmentosa in a transgenic mouse model.

Retinitis pigmentosa (RP) is a group of progressive retinal degenerations of mostly monogenic inheritance, which cause blindness in about 1:3,500 individuals worldwide. Heterozygous variants in the rhodopsin (RHO) gene are the most common cause of autosomal dominant RP (adRP). Among these, missense variants at C-terminal proline 347, such as p.Pro347Ser, cause severe adRP recurrently in European affected individuals. Here, for the first time, we use CRISPR/Cas9 to selectively target the p.Pro347Ser variant while preserving the wild-type RHO allele in vitro and in a mouse model of adRP. Detaile

Detection of the HLA-DQB1*06:02:43 allele in a Taiwanese leukemic patient.

One nucleotide substitution in codon 57 of HLA-DQB1*06:02:01:01 results in a novel allele, HLA-DQB1*06:02:43.

Detection of the HLA-B*18:116 allele in a Singaporean bone marrow donor.

One nucleotide substitution in codon 120 of HLA-B*18:01:01:01 results in a novel allele, HLA-B*18:116.

Recognition of the HLA-C*03:88 allele in a Singaporean bone marrow donor.

One nucleotide substitution in codon 108 of HLA-C*03:03:01:01 results in a novel allele, HLA-C*03:88.

Detection of the HLA-A*11:32:01 allele in a Taiwanese bone marrow donor.

One nucleotide substitution in codon 182 of HLA-A*11:01:01:01 results in a novel allele, HLA-A*11:32:01.

Detection of the HLA-B*15:404 allele in a Singaporean bone marrow donor.

Nucleotide substitutions in codons 67 and 119 of HLA-B*15:02:01:01 result in a novel allele, HLA-B*15:404.

The novel HLA-A allele, HLA-A*33:221, first described in a Brazilian individual.

The novel HLA-A*33:221 allele, first described in a potential bone marrow donor from Brazil.