ABSTRACT
We characterized 549 new human leukocyte antigen (HLA) class I and class II alleles found in newly registered stem cell donors as a result of high-throughput HLA typing. New alleles include 101 HLA-A, 132 HLA-B, 105 HLA-C, 2 HLA-DRB1, 89 HLA-DQB1 and 120 HLA-DPB1 alleles. Mainly, new alleles comprised single nucleotide variations when compared with homologous sequences. We identified nonsynonymous nucleotide mutations in 70.7% of all new alleles, synonymous variations in 26.4% and nonsense substitutions in 2.9% (null alleles). Some new alleles (55, 10.0%) were found multiple times, HLA-DPB1 alleles being the most frequent among these. Furthermore, as several new alleles were identified in individuals from ethnic minority groups, the relevance of recruiting donors belonging to such groups and the importance of ethnicity data collection in donor centers and registries is highlighted.
Subject(s)
Alleles , Genetic Loci , HLA Antigens/genetics , Stem Cells/immunology , Tissue Donors , Ethnicity , Gene Expression , Gene Frequency , Germany , HLA Antigens/classification , HLA Antigens/immunology , Humans , Poland , Polymorphism, Single Nucleotide , Protein Isoforms/classification , Protein Isoforms/genetics , Protein Isoforms/immunology , Stem Cell Transplantation , Stem Cells/cytology , United StatesABSTRACT
We have characterized 372 novel human leukocyte antigen (HLA) class II alleles identified in newly registered stem cell donors, this includes 281 HLA-DRB1 alleles, 89 HLA-DQB1 alleles and 2 HLA-DPB1 alleles. Most novel alleles were single nucleotide variants when compared to their respective most homologous alleles. In 66.4% of all novel alleles non-synonymous nucleotide variations were identified, in 30.4% synonymous substitutions and in 3.2% nonsense mutations. Ninty-three (25.0%) novel alleles were found in several individuals; most often these were novel HLA-DRB1 alleles. Lastly, we underline the importance of recruiting ethnic minority donors in countries such as Germany and the United States, as novel alleles were frequently found among these groups.
Subject(s)
Alleles , Gene Frequency , HLA-DP beta-Chains/genetics , HLA-DQ beta-Chains/genetics , HLA-DRB1 Chains/genetics , Hematopoietic Stem Cell Transplantation , Living Donors , Codon, Nonsense , Female , Germany , Humans , Male , Poland , United StatesABSTRACT
We describe 2127 new human leukocyte antigen (HLA) class I alleles found in registered stem cell donors. These alleles represent 28.9% of the currently known class I alleles. Comparing new allele sequences to homologous sequences, we found 68.1% nonsynonymous nucleotide substitutions, 28.9% silent mutations and 3.0% nonsense mutations. Many substitutions occurred at positions that have not been known to be polymorphic before. A large number of HLA alleles and nucleotide variations underline the extreme diversity of the HLA system. Strikingly, 156 new alleles were found not only multiple times, but also in carriers of various parentage, suggesting that some new alleles are not necessarily rare. Moreover, new alleles were found especially often in minority donors. This emphasizes the benefits of specifically recruiting such groups of individuals.
Subject(s)
Alleles , Histocompatibility Antigens Class I/genetics , Stem Cells/metabolism , Tissue Donors , Base Sequence , Codon/genetics , Exons/genetics , Genetic Loci , Germany , Haplotypes/genetics , Humans , Mutation/genetics , Nucleotides/genetics , Poland , Registries , United StatesABSTRACT
Positron-emission tomography was coupled with neurological and neuropsychological evaluation to study regional cerebral activity and neurologic status in two groups. Seventeen patients with full-blown AIDS and 14 seronegative control subjects were studied using [18F]2-fluoro-2-deoxy-D-glucose in a resting state. The AIDS group had relative regional hypermetabolism in the basal ganglia and thalamus; stepwise multiple-regression analyses revealed a significant relationship for the AIDS group between temporal lobe metabolism and severity of dementia on the AIDS Dementia Complex Rating Scale. These results suggest that the basal ganglia, thalamus, and temporal lobes are differentially affected in AIDS.
Subject(s)
AIDS Dementia Complex/diagnostic imaging , Blood Glucose/metabolism , Energy Metabolism/physiology , Tomography, Emission-Computed , AIDS Dementia Complex/physiopathology , AIDS Dementia Complex/psychology , Adult , Brain/diagnostic imaging , Brain Mapping , Deoxyglucose/analogs & derivatives , Deoxyglucose/metabolism , Fluorodeoxyglucose F18 , Humans , Male , Middle Aged , Neurologic Examination , Neuropsychological TestsABSTRACT
Suicidal behavior in the United States from 1900 to 1975 is reviewed. The data presented cover demographic variables such as: age, sex, color, and geographic area. While the overall suicide rate continues to increase, the most striking upturn can be seen in both sexes between the ages of 15 to 25 years. The need for a wide range of innovative approaches and increased research is manifest.
