ALBERT

Description: Congenital cataracts are a significant cause of visual impairment or blindness in children. One-third of cases estimated to have a genetic cause. We carried out gene analysis and bioinformatics analysis to map the locus and to identify the underlying genetic defect in a 12-member, four-generation Chinese family affected with bilateral congenital cataracts. We screened individuals of the family and discovered a distinct missense mutation in HSF4 (a gene at this locus that encodes teat-shock transcription factor 4). Bioinformatics analysis was used to determine possible changes in the protein structure that could affect the phenotype. Sequencing of the candidate genes showed a heterozygous c.69 G-〉T change in the heat shock transcription factor 4 ( HSF4 ) gene, which resulted in the substitution of a lysine with an asparagine (p. K23N). This mutation cosegregated with all affected individuals and was not observed in unaffected family members. Bioinformatics analysis indicated that the p. K23N mutation was predicted to be disease causing. This is the first report of the novel missense mutation, c.69 G-〉T (p. K23N), in exon 3 of the HSF4 locus on 16q21-q22 associated with bilateral congenital cataracts in a Chinese family. This novel mutation could enable propergenetic diagnostics and counseling in affected families and could lead to a better understanding of the structure and function of HSF4 in health and disease.

Description: The signal transducer and activator of transcription 3 (STAT3) is a transcription factor that, when dysregulated, becomes a powerful oncogene found in many human cancers, including diffuse large B-cell lymphoma. Diffuse large B-cell lymphoma is the most common form of non-Hodgkin’s lymphoma and has two major subtypes: germinal center B-cell–like and activated B–cell—like. Compared with the germinal center B-cell–like form, activated B-cell–like lymphomas respond much more poorly to current therapies and often exhibit overexpression or overactivation of STAT3. To investigate how STAT3 might contribute to this aggressive phenotype, we have integrated genome-wide studies of STAT3 DNA binding using chromatin immunoprecipitation-sequencing with whole-transcriptome profiling using RNA-sequencing. STAT3 binding sites are present near almost a third of all genes that differ in expression between the two subtypes, and examination of the affected genes identified previously undetected and clinically significant pathways downstream of STAT3 that drive oncogenesis. Novel treatments aimed at these pathways may increase the survivability of activated B-cell–like diffuse large B-cell lymphoma.

Description: We constructed a very-high-density, whole-genome marker map (WGMM) for cotton by using 18,597 DNA markers corresponding to 48,958 loci that were aligned to both a consensus genetic map and a reference genome sequence. The WGMM has a density of one locus per 15.6 kb, or an average of 1.3 loci per gene. The WGMM was anchored by the use of colinear markers to a detailed genetic map, providing recombinational information. Mapped markers occurred at relatively greater physical densities in distal chromosomal regions and lower physical densities in the central regions, with all 1 Mb bins having at least nine markers. Hotspots for quantitative trait loci and resistance gene analog clusters were aligned to the map and DNA markers identified for targeting of these regions of high practical importance. Based on the cotton D genome reference sequence, the locations of chromosome structural rearrangements plotted on the map facilitate its translation to other Gossypium genome types. The WGMM is a versatile genetic map for marker assisted breeding, fine mapping and cloning of genes and quantitative trait loci, developing new genetic markers and maps, genome-wide association mapping, and genome evolution studies.

Description: Japanese flounder ( Paralichthys olivaceus ) is one of the economic important fish in China. Sexual dimorphism, especially the different growth rates and body sizes between two sexes, makes this fish a good model to investigate mechanisms responsible for such dimorphism for both fundamental questions in evolution and applied topics in aquaculture. However, the lack of "omics" data has hindered the process. The recent advent of RNA-sequencing technology provides a robust tool to further study characteristics of genomes of nonmodel species. Here, we performed de novo transcriptome sequencing for a double haploid Japanese flounder individual using Illumina sequencing. A single lane of paired-end sequencing produced more than 27 million reads. These reads were assembled into 107,318 nonredundant transcripts, half of which (51,563; 48.1%) were annotated by blastx to public protein database. A total of 1051 genes that had potential alternative splicings were detected by Chrysalis implemented in Trinity software. Four of 10 randomly picked genes were verified truly containing alternative splicing by cloning and Sanger sequencing. Notably, using a doubled haploid Japanese flounder individual allow us to analyze gene duplicates. In total, 3940 "single-nucleotide polymorphisms" were detected form 1859 genes, which may have happened gene duplicates. This study lays the foundation for structural and functional genomics studies in Japanese flounder.

Description: Meiotic nonreduction resulting in unreduced gametes is thought to be the predominant mechanism underlying allopolyploid formation in plants. Until now, however, its genetic base was largely unknown. The allohexaploid crop common wheat ( Triticum aestivum L.), which originated from hybrids of T. turgidum L. with Aegilops tauschii Cosson, provides a model to address this issue. Our observations of meiosis in pollen mother cells from T. turgidum x Ae. tauschii hybrids indicated that first division restitution, which exhibited prolonged cell division during meiosis I, was responsible for unreduced gamete formation. A major quantitative trait locus (QTL) for this trait, named QTug.sau-3B , was detected on chromosome 3B in two T. turgidum x Ae. tauschii haploid populations. This QTL is situated between markers Xgwm285 and Xcfp1012 and covered a genetic distance of 1 cM in one population. QTug.sau-3B is a haploid-dependent QTL because it was not detected in doubled haploid populations. Comparative genome analysis indicated that this QTL was close to Ttam-3B , a collinear homolog of tam in wheat. Although the relationship between QTug.sau-3B and Ttam requires further study, high frequencies of unreduced gametes may be related to reduced expression of Ttam in wheat.

Description: Bats comprise 20% of all mammalian species and display a number of characteristics, including true flight, echolocation, and a heightened ability to resist viral load that uniquely position this group for comparative genomic studies. Here we searched for evidence of genomic variation consistent with sensory rewiring through bat evolution. We focused on two species with divergent sensory preferences. Myotis davidii is a bat species that echolocates and possesses dim- but not daylight-adapted vision whereas the black flying fox ( Pteropus alecto) has highly developed day vision but does not echolocate. Using the naked mole rat as a reference, we found five functional genes ( CYP1A2 , RBP3 , GUCY2F , CRYBB1 , and GRK7 ) encoding visual proteins that have degenerated into pseudogenes in M. davidii but not P. alecto . In a second approach genome-wide codon usage bias (CUB) was compared between the two bat species. This CUB ranking systematically enriched for vision-related ( CLN8 , RD3 , IKZF1 , LAMC3 , CRX , SOX8 , VAX2 , HPS1 , RHO , PRPH2 , and SOX9 ) and hearing-related ( TPRN , TMIE , SLC52A3 , OTOF , WFS1 , SOD1 , TBX18 , MAP1A , OTOS , GPX1 , and USH1G ) machinery in M. davidii but not P. alecto . All vision and hearing genes selectively enriched in M. davidii for which orthologs could be identified also were more biased in the echolocating M. lucifugus than the nonecholocating P. vampyrus . We suggest that the existence of codon bias in vision- and hearing-related genes in a species that has evolved echolocation implies CUB is part of evolution’s toolkit to rewire sensory systems. We propose that the two genetic changes (pseudogene formation and CUB) collectively paint a picture of that incorporates a combination of destruction and gain-of-function. Together, they help explain how natural selection has reduced physiological costs associated with the development of a smaller eye poorly adapted to day vision but that also contribute to enhanced dim light vision and the hearing adaptations consonant with echolocation.

Description: The genome of potato, a major global food crop, was recently sequenced. The work presented here details the integration of the potato reference genome (DM) with a new sequence-tagged site marker–based linkage map and other physical and genetic maps of potato and the closely related species tomato. Primary anchoring of the DM genome assembly was accomplished by the use of a diploid segregating population, which was genotyped with several types of molecular genetic markers to construct a new ~936 cM linkage map comprising 2469 marker loci. In silico anchoring approaches used genetic and physical maps from the diploid potato genotype RH89-039-16 (RH) and tomato. This combined approach has allowed 951 superscaffolds to be ordered into pseudomolecules corresponding to the 12 potato chromosomes. These pseudomolecules represent 674 Mb (~93%) of the 723 Mb genome assembly and 37,482 (~96%) of the 39,031 predicted genes. The superscaffold order and orientation within the pseudomolecules are closely collinear with independently constructed high density linkage maps. Comparisons between marker distribution and physical location reveal regions of greater and lesser recombination, as well as regions exhibiting significant segregation distortion. The work presented here has led to a greatly improved ordering of the potato reference genome superscaffolds into chromosomal "pseudomolecules".

Description: The yeast Hsp110 chaperone Sse1 is a conserved protein that is a noncanonical member of the Hsp70 protein superfamily. Sse1 influences the cellular response to heat stress and has also been implicated in playing a role in the propagation of prions in yeast. Sse1 can seemingly exert its effects in vivo through direct or indirect actions by influencing the nucleotide exchange activity of canonical cytosolic Hsp70s. Using a genetic screen based on the inability to propagate the yeast [ PSI + ] prion, we have identified 13 new Sse1 mutants that are predicted to alter chaperone function through a variety of different mechanisms. Not only are these new Sse1 mutants altered in the ability to propagate and cure yeast prions but also to varying degrees in the ability to grow at elevated temperatures. The expression levels of chaperone proteins known to influence yeast prion propagation are unaltered in the Sse1 mutants, suggesting that the observed phenotypic effects are caused by direct functional alterations in these mutants. Mapping the location of the mutants onto the Sse1 crystal structure suggests that more than one functional alteration in Sse1 may result in changes in prion propagation and ability to function at elevated temperatures. All Sse1 mutants isolated provide essential functions in the cell under normal growth conditions, further demonstrating that essential chaperone functions in vivo can to some degree at least be detached from those related to propagation of prions. Our results suggest that Sse1 can influence prion propagation through a variety of different mechanisms.

Description: Daily PM2.5 (aerosol particles with an aerodynamic diameter of less than 2.5 μm) samples were collected at an urban site in Chengdu, an inland megacity in southwest China, during four 1-month periods in 2011, with each period in a different season. Samples were subject to chemical analysis for various chemical components ranging from major water-soluble ions, organic carbon (OC), element carbon (EC), trace elements to biomass burning tracers, anhydrosugar levoglucosan (LG), and mannosan (MN). Two models, the ISORROPIA II thermodynamic equilibrium model and the positive matrix factorization (PMF) model, were applied to explore the likely chemical forms of ionic constituents and to apportion sources for PM2.5. Distinctive seasonal patterns of PM2.5 and associated main chemical components were identified and could be explained by varying emission sources and meteorological conditions. PM2.5 showed a typical seasonality of waxing in winter and waning in summer, with an annual mean of 119 μg m−3. Mineral soil concentrations increased in spring, whereas biomass burning species elevated in autumn and winter. Six major source factors were identified to have contributed to PM2.5 using the PMF model. These were secondary inorganic aerosols, coal combustion, biomass burning, iron and steel manufacturing, Mo-related industries, and soil dust, and they contributed 37 ± 18, 20 ± 12, 11 ± 10, 11 ± 9, 11 ± 9, and 10 ± 12%, respectively, to PM2.5 masses on annual average, while exhibiting large seasonal variability. On annual average, the unknown emission sources that were not identified by the PMF model contributed 1 ± 11% to the measured PM2.5 mass. Various chemical tracers were used for validating PMF performance. Antimony (Sb) was suggested to be a suitable tracer of coal combustion in Chengdu. Results of LG and MN helped constrain the biomass burning sources, with wood burning dominating in winter and agricultural waste burning dominating in autumn. Excessive Fe (Ex-Fe), defined as the excessive portion in measured Fe that cannot be sustained by mineral dust, is corroborated to be a straightforward useful tracer of iron and steel manufacturing pollution. In Chengdu, Mo / Ni mass ratios were persistently higher than unity, and considerably distinct from those usually observed in ambient airs. V / Ni ratios averaged only 0.7. Results revealed that heavy oil fuel combustion should not be a vital anthropogenic source, and additional anthropogenic sources for Mo are yet to be identified. Overall, the emission sources identified in Chengdu could be dominated by local sources located in the vicinity of Sichuan, a result different from those found in Beijing and Shanghai, wherein cross-boundary transport is significant in contributing pronounced PM2.5. These results provided implications for PM2.5 control strategies.

Description: With increasing NO2 concentration in the troposphere, the importance of NO2 reaction with mineral dust in the atmosphere needs to be evaluated. Until now, little is known about the reaction of NO2 with CaCO3. In this study, the heterogeneous reaction of NO2 on the surface of CaCO3 particles was investigated at 296 K and NO2 concentrations between 4.58×1015 molecules cm−3 to 1.68×1016 molecules cm−3, using diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) combined with X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM), under wet and dry conditions. Nitrate formation was observed under both conditions, while nitrite was observed under wet conditions, indicating the reaction of NO2 on the CaCO3 surface produced nitrate and probably nitrous acid (HONO). Relative humidity (RH) influences both the initial uptake coefficient and the reaction mechanism. At low RH, surface −OH is formed through dissociation of the surface adsorbed water via oxygen vacancy, thus determining the reaction order. As RH increases, water starts to condense on the surface and the gas-liquid reaction of NO2 with the condensed water begins. With high enough RH (〉52% in our experiment), the gas-liquid reaction of NO2 with condensed water becomes dominant, forming HNO3 and HONO. The initial uptake coefficient γ0 was determined to be (4.25±1.18)×10−9 under dry conditions and up to (6.56±0.34)×10−8 under wet conditions. These results suggest that the reaction of NO2 on CaCO3 particle is unable to compete with that of HNO3 in the atmosphere. Further studies at lower NO2 concentrations and with a more accurate assessment of the surface area for calculating the uptake coefficient of the reaction of NO2 on CaCO3 particle and to examine its importance as a source of HONO in the atmosphere are needed.