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Yize Zhao, Hongtu Zhu, Zhaohua Lu, Rebecca C Knickmeyer, Fei Zou
It becomes increasingly important in using genome-wide association studies (GWAS) to select important genetic information associated with qualitative or quantitative traits. Currently, the discovery of biological association among SNPs motivates various strategies to construct SNP-sets along the genome and to incorporate such set information into selection procedure for a higher selection power, while facilitating more biologically meaningful results. The aim of this paper is to propose a novel Bayesian framework for hierarchical variable selection at both SNP-set (group) level and SNP (within group) level...
April 22, 2019: Genetics
Kuo-Fang Shen, Susan L Forsburg
Fission yeast Swi6 is a human HP-1 homologue that plays important roles in multiple cellular processes. In addition to its role in maintaining heterochromatin silencing, Swi6 is required for cohesin enrichment at the pericentromere. Loss of Swi6 leads to abnormal mitosis including defects in establishment of bi-oriented sister kinetochores and microtubule attachment. Swi6 interacts with Dfp1, a regulatory subunit of DDK kinase, and failure to recruit Dfp1 to the pericentromere results in late DNA replication...
April 18, 2019: Genetics
Yukihiko Kubota, Kiyoji Nishiwaki, Masahiro Ito, Asako Sugimoto
Remodeling of the extracellular matrix supports tissue and organ development by regulating cellular morphology and tissue integrity. However, proper extracellular matrix remodeling requires spatiotemporal regulation of extracellular metalloproteinase activity. Members of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family, including MIG-17 and GON-1, are evolutionarily conserved, secreted zinc-requiring metalloproteinases. Although these proteases are required for extracellular matrix remodeling during gonadogenesis in Caenorhabditis elegans , their in vivo regulatory mechanisms remain to be delineated...
April 16, 2019: Genetics
Omera B Matoo, Cole R Julick, Kristi L Montooth
Organismal physiology emerges from metabolic pathways and subcellular structures like the mitochondria that can vary across development and among individuals. Here we tested whether genetic variation at one level of physiology can be buffered at higher biological levels of organization during development by the inherent capacity for homeostasis in physiological systems. We found that the fundamental scaling relationship between mass and metabolic rate, as well as the oxidative capacity per mitochondria, changed significantly across development in the fruit fly Drosophila However, mitochondrial respiration rate was maintained at similar levels across development...
April 11, 2019: Genetics
Siwei He, Andrea Cuentas-Condori, David M Miller
GFP labeling by genome editing can reveal the authentic location of a native protein but is frequently hampered by weak GFP signals and broad expression across a range of tissues that may obscure cell-specific localization. To overcome these problems, we engineered a <u>N</u>ative <u>A</u>nd <u>T</u>issue-specific <u>F</u>luorescence (NATF) strategy which combines CRISPR/Cas-9 and split-GFP to yield bright, cell-specific protein labeling. We use CRISPR/Cas9 to insert a tandem array of seven copies of the GFP11 ß-strand ( gfp11x7 ) at the genomic locus of each target protein...
April 5, 2019: Genetics
Thorsten Stefan, Louise Matthews, Joaquin M Prada, Colette Mair, Richard Reeve, Michael J Stear
The Major Histocompatibility Complex (MHC) is the most genetically diverse region of the genome in most vertebrates. Some form of balancing selection is necessary to account for the extreme diversity, but the precise mechanism of balancing selection is unknown. Due to the way MHC molecules determine immune recognition, overdominance (also referred to as heterozygote advantage) has been suggested as the main driving force behind this unrivalled diversity. However, both theoretical results and simulation models have shown that overdominance in its classical form cannot maintain large numbers of alleles unless all alleles confer unrealistically similar levels of fitness...
April 5, 2019: Genetics
Pawel Piwko, Ilektra Vitsaki, Ioannis Livadaras, Christos Delidakis
Transvection is the phenomenon where a transcriptional enhancer activates a promoter located on the homologous chromosome. It has been amply documented in Drosophila where homologues are closely paired in most, if not all, somatic nuclei, but it has been known to rarely occur in mammals as well. We have taken advantage of site-directed transgenesis to insert reporter constructs into the same genetic locus in Drosophila and have evaluated their ability to engage in transvection by testing many heterozygous combinations...
April 4, 2019: Genetics
Rohan Dandage, Philippe C Després, Nozomu Yachie, Christian R Landry
CRISPR-mediated base editors have opened unique avenues for scar-free genome-wide mutagenesis. Here, we describe a comprehensive computational workflow called beditor that can be broadly adapted for designing guide RNA libraries with a range of CRISPR-mediated base editors, PAM recognition sequences and genomes of many species. Additionally, in order to assist users in selecting the best sets of guide RNAs for their experiments, a priori estimates, called beditor scores are calculated. These beditor scores are intended to select guide RNAs that conform to requirements for optimal base editing: the editable base falls within maximum activity window of the CRISPR-mediated base editor and produces non-confounding mutational effects with minimal predicted off-target effects...
April 1, 2019: Genetics
Alissa L Severson, Shai Carmi, Noah A Rosenberg
Consanguineous unions increase the rate at which identical genomic segments are paired within individuals to produce runs of homozygosity (ROH). The extent to which such unions affect identity-by-descent (IBD) genomic sharing between rather than within individuals in a population, however, is not immediately evident from within-individual ROH levels. Using the fact that the time to the most recent common ancestor ( T MRCA ) for a pair of genomes at a specific locus is inversely related to the extent of IBD sharing between the genomes in the neighborhood of the locus, we study IBD sharing for a pair of genomes sampled either within the same individual or in different individuals...
March 29, 2019: Genetics
José Luis Campos, Brian Charlesworth
Levels of variability and rates of adaptive evolution may be affected by hitchhiking, the effect of selection on evolution at linked sites. Hitchhiking can be caused either by selective sweeps or by background selection, involving the spread of new favorable alleles or the elimination of deleterious mutations, respectively. Recent analyses of population genomic data have fitted models where both these processes act simultaneously, in order to infer the parameters of selection. Here, we investigate the consequences of relaxing a key assumption of some of these studies - that the time occupied by a selective sweep is negligible compared with the neutral coalescent time...
March 28, 2019: Genetics
Nicholas A Rhoades, Austin M Harvey, Dilini A Samarajeewa, Jesper Svedberg, Aykhan Yusifov, Anna Abusharekh, Pennapa Manitchotpisit, Daren W Brown, Kevin J Sharp, David G Rehard, Joshua Peters, Xavier Ostolaza-Maldonado, Jackson Stephenson, Patrick K T Shiu, Hanna Johannesson, Thomas M Hammond
Sk‑2 is a meiotic drive element that was discovered in wild populations of Neurospora fungi over forty years ago. While early studies quickly determined that Sk-2 transmits itself through sexual reproduction in a biased manner via spore killing, the genetic factors responsible for this phenomenon have remained mostly unknown. Here, we identify and characterize rfk‑1, a gene required for Sk-2 -based spore killing. The rfk‑1 gene contains four exons, three introns, and two stop codons, the first of which undergoes RNA editing to a tryptophan codon during sexual development...
March 27, 2019: Genetics
Jackson Champer, Zhaoxin Wen, Anisha Luthra, Riona Reeves, Joan Chung, Chen Liu, Yoo Lim Lee, Jingxian Liu, Emily Yang, Philipp W Messer, Andrew G Clark
Gene drives could allow for control of vector-borne diseases by directly suppressing vector populations or spreading genetic payloads designed to reduce pathogen transmission. CRISPR homing gene drives work by cleaving wild-type alleles, which are then converted to drive alleles by homology-directed repair, increasing the frequency of the drive in a population over time. However, resistance alleles can form when end-joining repair takes place in lieu of homology-directed repair. Such alleles cannot be converted to drive alleles, which would eventually halt the spread of a drive through a population...
March 27, 2019: Genetics
Andreas Rechtsteiner, Meghan E Costello, Thea A Egelhofer, Jacob M Garrigues, Susan Strome, Lisa N Petrella
Repression of germline-promoting genes in somatic cells is critical for somatic development and function. To study how germline genes are repressed in somatic tissues, we analyzed key histone modifications in three Caenorhabditis elegans synMuv B mutants, lin-15B, lin-35, and lin-37 , all of which display ectopic expression of germline genes in the soma. LIN-35 and LIN-37 are members of the conserved DREAM complex. LIN-15B has been proposed to work with the DREAM complex but has not been shown biochemically to be a member of the complex...
March 25, 2019: Genetics
Morgane Roth, Ana M Florez-Rueda, Thomas Städler
Parental imbalances in the endosperm leading to impaired development and eventual hybrid seed failure are common causes of postzygotic isolation in flowering plants. Endosperm sensitivity to parental dosage is reflected by canonical phenotypes of 'parental excess' in reciprocal interploid crosses. Moreover, parental-excess traits are also evident in many homoploid interspecific crosses, potentially reflecting among-lineage variation in 'effective ploidy' driven by endosperm properties. However, the genetic basis of effective ploidy is unknown and genome-wide expression perturbations in parental-excess endosperms from homoploid crosses have yet to be reported...
March 22, 2019: Genetics
Yu-Hsuan Lai, Krishna Choudhary, Sara C Cloutier, Zheng Xing, Sharon Aviran, Elizabeth J Tran
RNA helicases are a class of enzymes that unwind RNA duplexes in vitro but whose cellular functions are largely enigmatic . Here, we provide evidence that the DEAD-box protein Dbp2 remodels RNA-protein complex (RNP) structure to facilitate efficient termination of transcription in S. cerevisiae via the Nrd1-Nab3-Sen1 (NNS) complex. First, we find that loss of DBP2 results in RNA polymerase II (RNAPII) accumulation at the 3' ends of snoRNAs and a subset of mRNAs. In addition, Dbp2 associates with RNA sequence motifs and regions bound by Nrd1 and can promote its recruitment to NNS-targeted regions...
March 22, 2019: Genetics
Alena A Kozlova, Michelle Lotfi, Peter G Okkema
Precise signaling at the neuromuscular junction (NMJ) is essential for proper muscle contraction. In the Caenorhabditis elegans pharynx, acetylcholine (ACh) released from the MC and M4 motor neurons stimulates two different types of contractions in adjacent muscle cells, termed pumping and isthmus peristalsis. MC stimulates rapid pumping through the nicotinic ACh receptor EAT-2, which is tightly localized at the MC NMJ, and eat-2 mutants exhibit a slow pump rate. Surprisingly, we found that eat-2 mutants also hyperstimulated peristaltic contractions, and these are characterized by increased and prolonged Ca2+ transients in the isthmus muscles...
March 21, 2019: Genetics
David A Brow
Selection of suppressor mutations that correct growth defects caused by substitutions in an RNA or protein can reveal functionally important molecular structures and interactions in living cells. This approach is particularly useful for the study of complex biological pathways involving many macromolecules, such as pre-messenger RNA splicing. When a sufficiently large number of suppressor mutations is obtained and structural information is available, it is possible to generate detailed models of molecular function...
March 21, 2019: Genetics
Alexandre P Marand, Shelley H Jansky, Joseph L Gage, Andy J Hamernik, Natalia de Leon, Jiming Jiang
Deconvolution of the genetic architecture underlying yield is critical for understanding bases of genetic gain in species of agronomic importance. To dissect the genetic components of yield in potato, we adopted a reference-based recombination map composed of four segregating alleles from an interspecific pseudo-testcross F1 potato population (n=90). Approximately 1.5 million short nucleotide variants were utilized during map construction, resulting in unprecedented resolution for an F1 population; estimated by a median bin length of 146-kb, and 11 genes per bin...
March 18, 2019: Genetics
Agnes Rettelbach, Alexander Nater, Hans Ellegren
There is an increasing awareness that selection affecting linked neutral sites strongly influences on how diversity is distributed across the genome. In particular, linked selection is likely involved in the formation of heterogenous landscapes of genetic diversity, including genomic regions with locally reduced effective population size that manifests as dips in diversity and "islands" of differentiation between closely related populations or species. Linked selection can be in the form of background selection or selective sweeps and a long-standing question in population genetics has been to unveil the relative importance of these processes...
March 14, 2019: Genetics
John S Poulton, Daniel J McKay, Mark Peifer
Centrosomes play a critical role in mitotic spindle assembly through their role in microtubule nucleation and bipolar spindle assembly. Loss of centrosomes can impair the ability of some cells to properly conduct mitotic division, leading to chromosomal instability, cell stress, and aneuploidy. Multiple aspects of the cellular response to mitotic error associated with centrosome loss appears to involve activation of JNK signaling. To further characterize the transcriptional effects of centrosome loss, we compared gene expression profiles of wildtype and acentrosomal cells from Drosophila wing imaginal discs...
March 13, 2019: Genetics
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