Clozapine-induced agranulocytosis is associated with rare HLA-DQB1 and HLA-B alleles.

Clozapine is a particularly effective antipsychotic medication but its use is curtailed by the risk of clozapine-induced agranulocytosis/granulocytopenia (CIAG), a severe adverse drug reaction occurring in up to 1% of treated individuals. Identifying genetic risk factors for CIAG could enable safer and more widespread use of clozapine. Here we perform the largest and most comprehensive genetic study of CIAG to date by interrogating 163 cases using genome-wide genotyping and whole-exome sequencing.

Compound heterozygosity of HLA-DRB3*01:01 and HLA-DRB4*01:01 as a potential predictor of fetal neonatal alloimmune thrombocytopenia.

Background: Fetal neonatal alloimmune thrombocytopenia (FNAIT) is a life-threatening bleeding disorder in the fetus or neonate caused by maternal alloantibodies directed against fetal platelet (PLT) antigens inherited from the father. The immune-dominant antigen leading to severe FNAIT is the human PLT antigen (HPA)-1, whose polymorphism constitutes an epitope for human leukocyte antigens (HLAs), usually DRB3*0101 leading to an immune response.

Study Design And Methods: In this study our aims were to find whether other allele variants of the β subunit of the HLA-DR family specifically focused on the HLA residues that bind Position 33 of the HPA-1 integrin contribute to FNAIT development and affect response to treatment and whether coexistence of both anti-HPA-1a and anti-HLA class I specific against the father's antigens leads to a more severe thrombocytopenia in the newborn.

TMPRSS2/ERG promotes epithelial to mesenchymal transition through the ZEB1/ZEB2 axis in a prostate cancer model.

Prostate cancer is the most common non-dermatologic malignancy in men in the Western world. Recently, a frequent chromosomal aberration fusing androgen regulated TMPRSS2 promoter and the ERG gene (TMPRSS2/ERG) was discovered in prostate cancer. Several studies demonstrated cooperation between TMPRSS2/ERG and other defective pathways in cancer progression.

The effect of gentamicin-induced readthrough on a novel premature termination codon of CD18 leukocyte adhesion deficiency patients.

Background: Leukocyte adhesion deficiency 1 (LAD1) is an inherited disorder of neutrophil function. Nonsense mutations in the affected CD18 (ITB2) gene have rarely been described. In other genes containing such mutations, treatments with aminoglycoside types of antibiotics (e.

Thrombophilic polymorphisms in Israel.

Three thrombophilic polymorphisms, FV G1691A, FII G20210A and MTHFR C677T were investigated in Israeli populations by FRET, (fluorescence resonance energy transfer) real-time PCR. We observe extensive variability in the frequencies of each of the polymorphisms, as has been observed in the study of other polymorphisms in these populations. Very high allele frequencies for FV G1691A (the highest 0.

Typing classical polymorphisms by real-time PCR: analysis of the GPT and ALAD protein polymorphisms in the Jewish populations.

Expanding the already extensive data array on classical polymorphisms in new populations is beneficial to full characterization of the intricate relationships between human populations. This can be done in a short time on a large-scale by using real-time PCR. The red-cell enzymes Delta-aminolevulinate dehydratase (ALAD) and glutamate pyruvate transaminase (GPT) have each two alleles that can be separated by protein electrophoresis.

HLA-G expression is induced in Epstein-Barr virus-transformed B-cell lines by culture conditions.

Human leukocyte antigen-G (HLA-G) belongs to the nonclassical HLA class I family of genes presently designated as class Ib genes. It was found to be expressed mainly in placental tissue and in the thymus. Expression of HLA-G is induced by lymphokines such as interleukin-10 and has been associated with the escape of tumor cells from immune surveillance or with inhibition of graft rejection.

Distribution of HLA-B27 subtypes in ankylosing spondylitis in an Israeli population.

Background: The aim of this study was to investigate the contribution of the B27 subtypes to ankylosing spondylitis (AS) expression in a group of Jewish patients from Israel and to compare their distribution with that found in Mexican Mestizo patients. Several HLA-B27 alleles have been clearly associated with AS. Among them, B( *)2705 and B( *)2702 are involved in susceptibility in different populations worldwide.

Characterization of HPSE gene single nucleotide polymorphisms in Jewish populations of Israel.

Heparanase is a mammalian endoglucuronidase responsible for heparan sulfate (HS) degradation. HS is a major constituent of the extracellular matrix (ECM) and HS-degrading activity plays a decisive role in fundamental biological processes associated with remodeling of the ECM, such as cancer metastasis, angiogenesis and inflammation. There is great interest in the prospect of genome-wide association studies to identify genetic factors underlying complex diseases.

Pemphigus vulgaris is associated with the transporter associated with antigen processing (TAP) system.

Pemphigus vulgaris (PV) is a human leukocute antigen (HLA) class II-associated autoimmune disease of the skin of unknown etiology. We recently described the association of pemphigus vulgaris with two clusters of microsatellite loci within the major histocompatibility complex region. One cluster includes the microsatellite marker TAP1CA, located in proximity to the transporter associated with antigen processing (TAP) genes.

The immunogenetics of pemphigus vulgaris.

Pemphigus vulgaris (PV) is an autoimmune blistering disease of the skin of unknown etiology. While various environmental factors have been implicated as triggering agents, HLA association is probably the most important predisposing factor. The aim of this review is to highlight the association of HLA with pemphigus vulgaris.

Genotype and allele frequencies of C3435T polymorphism of the MDR1 gene in various Jewish populations of Israel.

The human multidrug-resistant gene (MDR1) encodes for P-glycoprotein (P-gp), which is a membrane-bound efflux-transporter conferring resistance to a number of natural cytotoxic drugs and potentially toxic xenobiotics. The wobble C3435T polymorphism at exon 26 was associated with different expression levels of the MDR1 gene and substrate uptake. Differences in allele frequencies of the C3435T polymorphism have previously been demonstrated between racial groups.

Erroneous identification in a mixed population: simulation using Israeli STR data.

Allele distributions of 10 short tandem repeat (STR) polymorphic DNA loci used in forensic and paternity testing were determined for a cohort comprising 163 individuals representing a mixed Jewish Caucasian population. Typing was carried out by the commercial AmpF lSTR SGM Plus kit. The polymorphism and the utility of three of these markers for forensic studies in Israel were established for the first time.

HLA-G is associated with pemphigus vulgaris in Jewish patients.

Pemphigus is a group of life-threatening autoimmune blistering diseases of the skin and mucous membranes. The etiology and pathogenesis of this destructive autoimmune process remains unknown, but significant association with human leukocyte antigen (HLA) factors have been described in pemphigus vulgaris (PV) patient cohorts worldwide. We have recently analyzed DNA samples obtained from pemphigus patients and matched controls with a set of microsatellite markers, and found that markers mapped to HLA class I region are significantly associated with the disease.

Specific mutations in the HEXA gene among Iraqi Jewish Tay-Sachs disease carriers: dating of founder ancestor.

The incidence of Tay-Sachs disease (TSD) carriers, as defined by enzyme assay, is 1:29 among Ashkenazi Jews and 1:110 among Moroccan Jews. An elevated carrier frequency of 1:140 was also observed in the Iraqi Jews (IJ), while in other Israeli populations the world's pan-ethnic frequency of approximately 1:280 has been found. Recently a novel mutation, G749T, has been reported in 38.

Social and utilitarian considerations for allocating organs within a national organ sharing system: a computerized simulation model for policy decision-making.

Background: An organ-sharing system should achieve fairness and optimal graft longevity. Balancing between social and utilitarian considerations is a sensitive ethical, public and medical issue that requires a means to examine the consequences of any allocation policy or planned changes thereof.

Objective: To evaluate the performance and applicability of a computerized simulation model by examining the impact of two opposing organ allocation policies (social or utilitarian) on predicted organ distribution regarding age, waiting time, recipient sensitization measured by panel reactive antibody level, and overall donor-recipient tissue matching (measured by the number of HLA antigen mismatches).

Pemphigus vulgaris in Jewish patients is associated with HLA-A region genes: mapping by microsatellite markers.

Pemphigus vulgaris (PV) is the most severe autoimmune blistering disorder of the skin that is mediated by circulating autoantibodies against desmoglein 3 (Dsg3). It has been reported that in Jews the associated haplotype in PV is human leukocyte antigen (HLA) B38, DRB1*0402, DQB1*0302. Significant associations with HLA were observed also in non-Jews.