Search bioRxivSearch

Biology subjects

Miao, C.

Publications and source records attributed to Miao, C..

2 recordsLinked to original sources

Optimizing the identification of causal variants across varying genetic architectures in crops

BackgroundAssociation studies use statistical links between genetic markers and variation in a phenotypes value across many individuals to identify genes controlling variation in the target phenotype. However, this approach, particularly conducted on a genome-wide scale (GWAS), has limited power to identify the genes responsible for variation in traits controlled by complex genetic architectures.\n\nResultsHere we employ simulation studies utilizing real-world genotype datasets from association populations in four species with distinct minor allele frequency distributions, population structures, and patterns linkage disequilibrium to evaluate the impact of variation in both heritability and trait complexity on both conventional mixed linear model based GWAS and two new approaches specifically developed for complex traits. Mixed linear model based GWAS rapidly losses power for more complex traits. FarmCPU, a method based on multi-locus mixed linear models, provides the greatest statistical power for moderately complex traits. A Bayesian approach adopted from genomic prediction provides the greatest statistical power to identify causal genetic loci for extremely complex traits.\n\nConclusionsUsing estimates of the complexity of the genetic architecture of target traits can guide the selection of appropriate statistical methods and improve the overall accuracy and power of GWAS.

genomics

Systematically investigating the key features of the nuclease deactivated Cpf1 for tunable multiplex genetic regulation

With a unique crRNA processing capability, the CRISPR associated Cpf1 protein holds great potential for multiplex gene regulation. Unlike the well-studied Cas9 protein, however, conversion of Cpf1 to a transcription regulator and its related properties have not been systematically explored yet. In this study, we investigated the mutation schemes and crRNA requirements for the nuclease deactivated Cpf1 (dCpf1). By shortening the direct repeat sequence, we obtained genetically stable crRNA co-transcripts and improved gene repression with multiplex targeting. A screen of diversity-enriched PAM library was designed to investigate the PAM-dependency of gene regulation by dCpf1 from Francisella novicida and Lachnospiraceae bacterium. We found novel PAM patterns that elicited strong or medium gene repressions. Using a computational algorithm, we predicted regulatory outputs for all possible PAM sequences, which spanned a large dynamic range that could be leveraged for regulatory purposes. These newly identified features will facilitate the efficient design of CRISPR-dCpf1 based systems for tunable multiplex gene regulation.

synthetic biology