The quest for a donor: probability based methods offer help

When a patient in need of a stem cell transplant has no compatible donor within his or her closest family, and no matched unrelated donor can be found, a remaining option is to search within the patient’s extended family. This situation often arises when the patient is of an ethnic minority, originating from a country that lacks a well-developed stem cell donor program, and has HLA haplotypes that are rare in his or her country of residence. Searching within the extended family may be time-consuming and expensive, and tools to calculate the probability of a match within groups of untested relatives would facilitate the search. We present a general approach to calculating the probability of a match in a given relative, or group of relatives, based on the pedigree, and on knowledge of the genotypes of some of the individuals. The method extends previous approaches by allowing the pedigrees to be consanguineous and arbitrarily complex, with deviations from Hardy-Weinberg equilibrium. We show how this extension has a considerable effect on results, in particular for rare haplotypes. The methods are exemplified using freeware programs to solve a case of practical importance

Recruiting and retaining young people as voluntary blood donors

Objectives Reasons for predonation deferral of young potential donors and prospects of recruiting and retaining young people (age 18-29) as voluntary blood donors were studied. Results Twenty-five per cent of the first-time donors recruited in 1999 remained active in 2005, but the percentage was higher among older than younger donors. Change of residency was the most frequent reason for termination of donation among young donors. Young prospect donors were more frequently than older ones deferred for lifestyle-related reasons. Prospect donors older than 30 years were more frequently deferred for health-related reasons. A large proportion (57·7%) of young adults reported a favourable attitude towards becoming blood donors. Lack of a personal request (not being asked) was the most frequently reported reason for not giving blood among young people with no donation record. Only a minor proportion of young non-donors considered themselves disqualified from donating blood due to health status. Study Design and Methods Conclusions Lifestyle-related eligibility criteria and changes of residency pose problems for recruitment and retention of young donors. However, a large proportion of young adults state that they are able and willing to donate blood; therefore, the prospects of recruiting young people as voluntary blood donors seem generally positive. Key words: blood donors, blood donor recruitment and retention. Abbreviations and definitions BBO : Blood Bank of Oslo. Active donor : a person eligible for donation, who has donated blood or plasma regularly, at least once within the last 12 months. Lapsed donor : a person who has donated blood or plasma at least once, but not within the last 12 months. Non-donor : a person who has never donated blood or plasma. Prospect donor : a person appearing for first-time donor screening, who has never previously donated either blood or plasma

Histology and symplasmic tracer distribution during development of barley androgenic embryos

The present study concerns three aspects of barley androgenesis: (1) the morphology and histology of the embryos during their development, (2) the time course of fluorescent symplasmic tracers’ distribution, and (3) the correlation between symplasmic communication and cell differentiation. The results indicate that barley embryos, which are developing via an androgenic pathway, resemble their zygotic counterparts with respect to their developmental stages, morphology and histology. Analysis of the distribution of the symplasmic tracers, HPTS, and uncaged fluorescein indicates the symplasmic isolation of (1) the protodermis from the underlying cells of the late globular stage onwards, and (2) the embryonic organs at the mature stage of development

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues