Analysis of Allele Specific Expression——A Survey

Allele specific expression is essential for cellular programming and development and the diversity of cellular phenotypes. Traditional analysis methods utilize RNA and depend on single nucleotide polymorphisms,thus to suffer from limited amount of materials for analysis. The rapid development of next-generation sequencing technologies provides more comprehensive and powerful approaches to analyze the genomic, epigenetic, and transcriptomic data, and further to detect and measure allele specific expressions. It will potentially enhance the understanding of the allele specific expressions, their complexities, and the effect on biological processes. In this paper, we extensively review the state-of-art enabling technologies and tools to analyze, detect, and measure allele specific expressions, compare their features, and point out the future trend of the methods.

Significance of differential allelic expression in phenotypic plasticity and evolutionary potential of microbial eukaryotes

Background:Differential allelic expression(DAE)plays a key role in the regularion of many biological processes,and it may also play a role in adaptive evolution.Recently,environment-dependent DAE has been observed in species of marine phytoplankton,and most remarkably,alleles that showed the highest level of DAE also showed the fastest rate of evolution.Methods:To better understand the role of DAE in adaptive evolution and phenotypic plasticity,we developed a 2-D cellular automata model“DAEsy-World”that builds on the classical Daisyworld model.Results:Simulations show that DAE delineates the evolution of alternative alleles of a gene,enabling the two alleles to adapt to different environmental conditions and sub-functionalize.With DAE,the build-up of genetic polymorphisms within genes is driven by positive selection rather than strict neutral evolution,and this can enhance phenotypic plasticity.Moreover,in sexually reproducing organisms,DAE also increased the standing genetic variation,augmenting a species’adaptive evolutionary potential and ability to respond to fluctuating and/or changing conditions(cf,genetic assimilation).We furthermore show that DAE is likely to evolve in fluctuating environmental conditions.Conclusions:DAE increases the adaptive evolutionary potential of both sexual and asexually reproducing organisms,and it may affect the pattern of nucleotide substitutions of genes.

Heterozygous CARD9 mutation favors the development of allergic bronchopulmonary aspergillosis

Background:Previous research demonstrated that a homozygous mutation of g.136372044G>A(S12N)in caspase recruitment domain family member 9(CARD9)is critical for producing Aspergillus fumigatus-induced(Af-induced)T helper 2(T_(H)2)-mediated responses in allergic bronchopulmonary aspergillosis(ABPA).However,it remains unclear whether the CARD9^(S12N)mutation,especially the heterozygous occurrence,predisposes the host to ABPA.Methods:A total of 61 ABPA patients and 264 controls(including 156 healthy controls and 108 asthma patients)were recruited for sequencing the CARD9 locus to clarify whether patients with this heterozygous single-nucleotide polymorphisms are predisposed to the development of ABPA.A series of in vivo and in vitro experiments,such as quantitative real-time polymerase chain reaction,flow cytometry,and RNA isolation and quantification,were used to illuminate the involved mechanism of the disease.Results:The presence of the p.S12N mutation was associated with a significant risk of ABPA in ABPA patients when compared with healthy controls and asthma patients,regardless of Aspergillus sensitivity.Relative to healthy controls without relevant allergies,the mutation of p.S12N was associated with a significant risk of ABPA(OR:2.69 and 4.17 for GA and AA genotypes,P=0.003 and 0.029,respectively).Compared with patients with asthma,ABPA patients had a significantly higher heterozygous mutation(GA genotype),indicating that p.S12N might be a significant ABPA-susceptibility locus(aspergillus sensitized asthma:OR:3.02,P=0.009;aspergillus unsensitized asthma:OR:2.94,P=0.005).The mutant allele was preferentially expressed in ABPA patients with heterozygous CARD9^(S12N),which contributes to its functional alterations to facilitate Af-induced T_(H)2-mediated ABPA development.In terms of mechanism,Card9 wild-type(Card9^(WT))expression levels decreased significantly due to Af-induced decay of its messenger RNA compared to the heterozygous Card9 S12N.In addition,ABPA patients with heterozygous CARD9^(S12N)had increased Af-induced interleukin-5 production.Conclusion:Our study provides the genetic evidence showing that the heterozygous mutation of CARD9^(S12N),followed by allele expression imbalance of CARD9^(S12N),facilitates the development of ABPA.

Assembly of yield heterosis of an elite rice hybrid is promising by manipulating dominant quantitative trait loci

In the past,rice hybrids with strong heterosis have been obtained empirically,by developing and testing thousands of combinations.Here,we aimed to determine whether heterosis of an elite hybrid could be achieved by manipulating major quantitative trait loci.We used 202 chromosome segment substitution lines from the elite hybrid Shanyou 63 to evaluate single segment heterosis(SSH)of yield per plant and identify heterotic loci.All nine detected heteroticloci acted in a dominant fashion,and no SSH exhibited overdominance.Functional alleles of key yield-related genes Ghd7,Ghd7.1,Hd1,and GS3 were dispersed in both parents.No functional alleles of three investigated genes were expressed at higher levels in the hybrids than in the more desirable parents.A hybrid pyramiding eight heterotic loci in the female parent Zhenshan 97 background had a comparable yield to Shanyou 63 and much higher yield than Zhenshan 97.Five hybrids pyramiding eight or nine heterotic loci in the combined parental genome background showed similar yield performance to that of Shanyou 63.These results suggest that dominance underlying functional complementation is an important contributor to yield heterosis and that heterosis assembly might be successfully promised by manipulating several major dominant heterotic loci.