Search

The 1000 Genomes Project aims to provide a deep characterization of human genome sequence variation by sequencing at a level that should allow the genome-wide detection of most variants with frequencies as low as 1%. However, in the major histocompatibility complex (MHC), only the top 10 most frequent haplotypes are in the 1% frequency range whereas thousands of haplotypes are present at lower frequencies. Given the limitation of both the coverage and the read length of the sequences generated by the 1000 Genomes Project, the highly variable positions that define HLA alleles may be difficult to identify. We used classical Sanger sequencing techniques to type the HLA-A, HLA-B, HLA-C, HLA-DRB1 and HLA-DQB1 genes in the available 1000 Genomes samples and combined the results with the 103,310 variants in the MHC region genotyped by the 1000 Genomes Project. Using pairwise identity-by-descent distances between individuals and principal component analysis, we established the relationship between ancestry and genetic diversity in the MHC region. As expected, both the MHC variants and the HLA phenotype can identify the major ancestry lineage, informed mainly by the most frequent HLA haplotypes. To some extent, regions of the genome with similar genetic or similar recombination rate have similar properties. An MHC-centric analysis underlines departures between the ancestral background of the MHC and the genome-wide picture. Our analysis of linkage disequilibrium (LD) decay in these samples suggests that overestimation of pairwise LD occurs due to a limited sampling of the MHC diversity. This collection of HLA-specific MHC variants, available on the dbMHC portal, is a valuable resource for future analyses of the role of MHC in population and disease studies.

Achieving excellent electrochemical performance at high charging rate has been a long-cherished dream in the field of lithium-ion batteries (LIBs). As a part of the efforts to meet the goal, an innovative strategy for the synthesis of 3D porous highly graphitic carbon microspheres, to which numerous hollow metal oxide nanospheres are anchored, for use as anode in LIBs is introduced. Hollow carbon nanosphere-aggregated microspheres prepared from the spray drying process are graphitized with the aid of metal catalysts, and subsequent oxidation selectively removed amorphous carbon, leading to the formation of highly conductive graphitic carbon matrix. Numerous hollow metal oxide nanospheres formed simultaneously during the oxidation process via nanoscale Kirkendall diffusion are anchored onto the carbonaceous matrix, effectively reinforcing the structural integrity by alleviating volume changes and reducing lithium-ion diffusion lengths. The synergistic effect of combining hollow metal oxide nanospheres with high theoretical capacity with conductive carbon matrix led to accelerated electrochemical kinetics, resulting in high capacity at high charging rate. In addition, trapping the hollow metal oxide nanospheres inside hollow carbon nanospheres could effectively alleviate the volume changes, which led to high structural stability. When applied as LIB anodes, the microspheres exhibit a capacity of 411 mA h g−1 after 2500 cycles at 10.0 A g−1, with ~80% capacity retention. The anode exhibits a high capacity of 274 mA h g−1 at an extremely high current density of 50.0 A g−1, thus demonstrating the structural merits of the microspheres. [ABSTRACT FROM AUTHOR]

Bone marrow transplantation is becoming a more common procedure. The procedure is used in treating leukemia, and in patients with marrow destroyed by chemotherapy or with marrow that is ineffective due to some congenital disorder. While many of the original attempts at bone marrow transplantation used matched bone marrow from donors within the patient's family, it has become increasingly more common to use unrelated donors. In fact, registries are being developed to improve the matches of bone marrow between patient and donor. Bone marrow transplantation has more potential complications, in contrast with many other sorts of transplantation. Not only might the patient's immune system attack and reject the grafted marrow, but immune cells within the grafted marrow may attack the patient's tissue in graft-versus-host disease. Since graft-versus-host disease seems to directly result from grafted T cells, donor bone marrow is now often depleted of T cells prior to transplantation. Unfortunately, the process of T cell depletion also increases the probability that the grafted bone marrow will be rejected. The authors report a case in which T cell depleted bone marrow was rejected by the recipient. The donor and recipient were compatible for the HLA histocompatibility antigens by serological testing and were also shown to be compatible by the mixed lymphocyte test, in which a cellular reaction can often be detected between incompatible antigens. Upon rejection, it was found that the patient had circulating T cells that seemed to react with a difference in the composition of the histocompatibility antigens of only one single amino acid. Both the donor and recipient were HLA-B44, but one was a variant classed as B44.1, while the other was B44.2. Investigation revealed that the only difference between these antigens was a leucine in the 156th position of B44.1, which was replaced by an aspartic acid in B44.2. While it cannot be concluded with certainty that this difference was responsible for the rejection of the grafted bone marrow, the identification within the patient of T cells that recognized this difference strongly suggests that a single amino acid difference may have caused the rejection. (Consumer Summary produced by Reliance Medical Information, Inc.)