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BACKGROUND: Hematopoietic stem cell transplantation (HSCT) is potentially curative for severe aplastic anemia (SAA). Graft failure (GF) remains a life-threatening complication after HSCT. Preexisting anti-HLA antibodies, especially HLA-specific antibodies (DSA), have been demonstrated as a risk of GF.
METHODS: This report describes a woman with acquired SAA who presented with anti-HLA antibodies and GF. After the treatment of anti-HLA antibodies, engraftment was achieved through a second alternative donor HSCT. This work complied with the Declaration of Helsinki and the Declaration of Istanbul.
CONCLUSIONS: Based on our experience in treating this case, we hold that the presence of preoperative anti-HLA antibodies could discount the efficacy of HSCT and anti-HLA antibody screening should be performed before HSCT. Additionally, a second HSCT is feasible to prolong survival.

UNASSIGNED: A major locus for spontaneous haploid genome doubling was detected by a case-control GWAS in an exotic maize germplasm. The combination of double haploid breeding method with this locus leads to segregation distortion on genomic regions of chromosome five. Temperate maize (Zea mays L.) breeding programs often rely on limited genetic diversity, which can be expanded by incorporating exotic germplasm. The aims of this study were to perform characterization of inbred lines derived from the tropical BS39 population using different breeding methods, to identify genomic regions showing segregation distortion in lines derived by the DH process using spontaneous haploid genome doubling (SHGD), and use case-control association mapping to identify loci controlling SHGD. Four different sets were used: BS39_DH and BS39_SSD were derived from the BS39 population by DH and single-seed descendent (SSD) methods, and BS39 × A427_DH and BS39 × A427_SSD from the cross between BS39 and A427. A total of 663 inbred lines were genotyped. The analyses of gene diversity and genetic differentiation for the DH sets provided evidence of the presence of a SHGD locus near the centromere of chromosome 5. The case-control GWAS for the DH set also pinpointed this locus. Haplotype sharing analysis showed almost 100% exclusive contribution of the A427 genome in the same region on chromosome 5 of BS39 × A427_DH, presumably due to an allele in this region affecting SHGD. This locus enables DH line production in exotic populations without colchicine or other artificial haploid genome doubling.

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Vandenboschia speciosa is a highly vulnerable fern species, with a large genome (10.5 Gb). Haploid gametophytes and diploid sporophytes are perennial, can reproduce vegetatively, and certain populations are composed only of independent gametophytes. These features make this fern a good model: (1) for high-throughput analysis of satellite DNA (satDNA) to investigate possible evolutionary trends in satDNA sequence features; (2) to determine the relative contribution of satDNA and other repetitive DNAs to its large genome; and (3) to analyse whether the reproduction mode or phase alternation between long-lasting haploid and diploid stages influences satDNA abundance or divergence.
We analysed the repetitive fraction of the genome of this species in three different populations (one comprised only of independent gametophytes) using Illumina sequencing and bioinformatic analysis with RepeatExplorer and satMiner.
The satellitome of V. speciosa is composed of 11 satDNA families, most of them showing a short repeat length and being A + T rich. Some satDNAs had complex repeats composed of sub-repeats, showing high similarity to shorter satDNAs. Three families had particular structural features and highly conserved motifs. SatDNA only amounts to approx. 0.4 % of its genome. Likewise, microsatellites do not represent more than 2 %, but transposable elements (TEs) represent approx. 50 % of the sporophytic genomes. We found high resemblance in satDNA abundance and divergence between both gametophyte and sporophyte samples from the same population and between populations.
(1) Longer (and older) satellites in V. speciosa have a higher A + T content and evolve from shorter ones and, in some cases, microsatellites were a source of new satDNAs; (2) the satellitome does not explain the huge genome size in this species while TEs are the major repetitive component of the V. speciosa genome and mostly contribute to its large genome; and (3) reproduction mode or phase alternation between gametophytes and sporophytes does not entail accumulation or divergence of satellites.

CONCLUSIONS: Using landraces for broadening the genetic base of elite maize germplasm is hampered by heterogeneity and high genetic load. Production of DH line libraries can help to overcome these problems. Landraces of maize (Zea mays L.) represent a huge reservoir of genetic diversity largely untapped by breeders. Genetic heterogeneity and a high genetic load hamper their use in hybrid breeding. Production of doubled haploid line libraries (DHL) by the in vivo haploid induction method promises to overcome these problems. To test this hypothesis, we compared the line per se performance of 389 doubled haploid (DH) lines across six DHL produced from European flint landraces with that of four flint founder lines (FFL) and 53 elite flint lines (EFL) for 16 agronomic traits evaluated in four locations. The genotypic variance ([Formula: see text]) within DHL was generally much larger than that among DHL and exceeded also [Formula: see text] of the EFL. For most traits, the means and [Formula: see text] differed considerably among the DHL, resulting in different expected selection gains. Mean grain yield of the EFL was 25 and 62% higher than for the FFL and DHL, respectively, indicating considerable breeding progress in the EFL and a remnant genetic load in the DHL. Usefulness of the best 20% lines was for individual DHL comparable to the EFL and grain yield (GY) in the top lines from both groups was similar. Our results corroborate the tremendous potential of landraces for broadening the narrow genetic base of elite germplasm. To make best use of these \"gold reserves\", we propose a multi-stage selection approach with optimal allocation of resources to (1) choose the most promising landraces for DHL production and (2) identify the top DH lines for further breeding.

Fisher\'s (1930) Fundamental Theorem of Natural Selection (FTNS), and in particular the development of an explicit age-structured version of the theorem, is of everlasting interest. In a recent paper, Grafen (2015a) argues that Fisher regarded his theorem as justifying individual rather than population fitness maximization. The argument relies on a new definition of fitness in age-structured populations in terms of individual birth and death rates and age-specific reproductive values in agreement with a principle of neutrality. The latter are frequency-dependent and defined without reference to genetic variation. In the same paper, it is shown that the rate of increase in the mean of the breeding values of fitness weighted by the reproductive values, but keeping the breeding values constant as in Price (1972) is equal to the additive genetic variance in fitness. Therefore, this partial change is obtained by keeping constant not only the genotypic birth and death rates but also the mean age-specific birth and death rates from which the age-specific reproductive values are defined. In this paper we reaffirm that the Malthusian parameter which measures the relative rate of increase or decrease in reproductive value of each genotype in a continuous-time age-structured population is the definition of fitness used in Fisher\'s (1930) FTNS. This is shown by considering an age-structured asexual haploid population with constant age-specific birth and death (or survival) parameters for each type. Although the original statement of the FTNS is for a diploid population, this simplified haploid model allows us to address the definition of fitness meant in this theorem without the complexities and effects of a changing genic environment. In this simplified framework, the rate of change in mean fitness in continuous time is expected to be exactly equal to the genetic variance in fitness (or to the genetic variance in fitness divided by the mean fitness in discrete time), which can be seen as a generalized growth-rate theorem. This theorem is shown to hold with the Malthusian parameter used as the definition of fitness. Moreover, in the same framework, it is shown that a discrete-time version of Grafen\'s definition may lead to a decrease in mean fitness. In the limit of weak selection with the unit of time proportional to the inverse of the intensity of selection, however, this definition predicts the right population dynamics in agreement with the growth-rate theorem. This clarifies the domain of application of the new definition, at least as far as population dynamics is concerned, and reconciles the new definition with the original one.

BACKGROUND: High-throughput loss-of-function genetic screening tools in yeast or other model systems except in mammalian cells have been implemented to study human susceptibility to chemical toxicity. Here, we employed a newly developed human haploid cell (KBM7)-based mutagenic screening model (KBM7-mu cells) and examined its applicability in identifying genes whose absence allows cells to survive and proliferate in the presence of chemicals.
METHODS: KBM7-mu cells were exposed to 200 μM Chlorpyrifos (CPF), a widely used organophosphate pesticide, a dose causing approximately 50% death of cells after 48h of treatment. After a 2-3 week period of continuous CPF exposure, survived single cell colonies were recovered and used for further analysis. DNA isolated from these cells was amplified using Splinkerette PCR with specific designed primers, and sequenced to determine the genomic locations with virus insertion and identify genes affected by the insertion. Quantitative realtime reverse transcription PCR (qRT-PCR) was used to confirm the knockdown of transcription of identified target genes.
RESULTS: We identified total 9 human genes in which the cells carrying these genes conferred the resistance to CPF, including AGPAT6, AIG1, ATP8B2, BIK, DCAF12, FNBP4, LAT2, MZF1-AS1 and PPTC7. MZF1-AS1 is an antisense RNA and not included in the further analysis. qRT-PCR results showed that the expression of 6 genes was either significantly reduced or completely lost. There were no changes in the expression of DCAF12 and AGPAT6 genes between the KBM7-mu and the control KBM7 cells.
CONCLUSIONS: The KBM7-mu genetic screening system can be modified and applied to identify novel susceptibility genes in response to environmental toxicants, which could provide valuable insights into potential mechanisms of toxicity.

The evolutionary stability of haploid-diploid life cycles is still controversial. Mathematical models indicate that niche differences between ploidy phases may be a necessary condition for the evolution and maintenance of these life cycles. Nevertheless, experimental support for this prediction remains elusive. In the present work, we explored this hypothesis in natural populations of the brown alga Ectocarpus. Consistent with the life cycle described in culture, Ectocarpus crouaniorum in NW France and E. siliculosus in SW Italy exhibited an alternation between haploid gametophytes and diploid sporophytes. Our field data invalidated, however, the long-standing view of an isomorphic alternation of generations. Gametophytes and sporophytes displayed marked differences in size and, conforming to theoretical predictions, occupied different spatiotemporal niches. Gametophytes were found almost exclusively on the alga Scytosiphon lomentaria during spring whereas sporophytes were present year-round on abiotic substrata. Paradoxically, E. siliculosus in NW France exhibited similar habitat usage despite the absence of alternation of ploidy phases. Diploid sporophytes grew both epilithically and epiphytically, and this mainly asexual population gained the same ecological advantage postulated for haploid-diploid populations. Consequently, an ecological interpretation of the niche differences between haploid and diploid individuals does not seem to satisfactorily explain the evolution of the Ectocarpus life cycle.

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