scholarly journals NGS-based reverse genetic screen for common embryonic lethal mutations compromising fertility in livestock

2016 ◽  
Vol 26 (10) ◽  
pp. 1333-1341 ◽  
Author(s):  
Carole Charlier ◽  
Wanbo Li ◽  
Chad Harland ◽  
Mathew Littlejohn ◽  
Wouter Coppieters ◽  
...  
Genetics ◽  
1988 ◽  
Vol 120 (4) ◽  
pp. 977-986
Author(s):  
K J Kemphues ◽  
M Kusch ◽  
N Wolf

Abstract We have analyzed a set of linkage group (LG) II maternal-effect lethal mutations in Caenorhabditis elegans isolated by a new screening procedure. Screens of 12,455 F1 progeny from mutagenized adults resulted in the recovery of 54 maternal-effect lethal mutations identifying 29 genes. Of the 54 mutations, 39 are strict maternal-effect mutations defining 17 genes. These 17 genes fall into two classes distinguished by frequency of mutation to strict maternal-effect lethality. The smaller class, comprised of four genes, mutated to strict maternal-effect lethality at a frequency close to 5 X 10(-4), a rate typical of essential genes in C. elegans. Two of these genes are expressed during oogenesis and required exclusively for embryogenesis (pure maternal genes), one appears to be required specifically for meiosis, and the fourth has a more complex pattern of expression. The other 13 genes were represented by only one or two strict maternal alleles each. Two of these are identical genes previously identified by nonmaternal embryonic lethal mutations. We interpret our results to mean that although many C. elegans genes can mutate to strict maternal-effect lethality, most genes mutate to that phenotype rarely. Pure maternal genes, however, are among a smaller class of genes that mutate to maternal-effect lethality at typical rates. If our interpretation is correct, we are near saturation for pure maternal genes in the region of LG II balanced by mnC1. We conclude that the number of pure maternal genes in C. elegans is small, being probably not much higher than 12.


2014 ◽  
Vol 16 (suppl 5) ◽  
pp. v173-v173
Author(s):  
B. R. Tschida ◽  
A. R. Lowy ◽  
C. A. Marek ◽  
T. Ringstrom ◽  
T. C. Beadnell ◽  
...  

PLoS ONE ◽  
2008 ◽  
Vol 3 (5) ◽  
pp. e2121 ◽  
Author(s):  
Anna Matynia ◽  
Stephan G. Anagnostaras ◽  
Brian J. Wiltgen ◽  
Maress Lacuesta ◽  
Michael S. Fanselow ◽  
...  

2019 ◽  
Vol 12 (3) ◽  
pp. dmm037762 ◽  
Author(s):  
Laura E. Kuil ◽  
Nynke Oosterhof ◽  
Samuël N. Geurts ◽  
Herma C. van der Linde ◽  
Erik Meijering ◽  
...  

1988 ◽  
Vol 51 (2) ◽  
pp. 95-102 ◽  
Author(s):  
Monica J. Justice ◽  
Vernon C. Bode

SummaryThe quaking (qk) locus on mouse chromosome 17 has been defined by a single viable quaking allele. Three new alleles of quaking were selected after ENU mutagenesis by their failure to complement the quaking phenotype. The qkk2 allele was induced on wild-type chromatin and the qkkt1 and qkkt4 alleles were induced on t-chromatin. Each is a recessive embryonic lethal mutation. They fail to complement each other and are not complemented by the deletion, TtOrl. Homozygotes and hemizygotes die at 8–9·5 days gestation, but not at a single precise time. Because the classical quaking mutation complements the lethality of these new alleles, but they fail to complement its quaking phenotype (myelination defect), we conclude that the quaking+ function is required for embryonic survival as well as for myelination.


2009 ◽  
Vol 334 (1) ◽  
pp. 1-9 ◽  
Author(s):  
Lwaki Ebarasi ◽  
Liqun He ◽  
Kjell Hultenby ◽  
Minoru Takemoto ◽  
Christer Betsholtz ◽  
...  

PLoS Genetics ◽  
2012 ◽  
Vol 8 (3) ◽  
pp. e1002530 ◽  
Author(s):  
Laura-Oana Albulescu ◽  
Nevin Sabet ◽  
Mohanram Gudipati ◽  
Nicholas Stepankiw ◽  
Zane J. Bergman ◽  
...  

1992 ◽  
Vol 59 (2) ◽  
pp. 103-116 ◽  
Author(s):  
David Jonah Grunwald ◽  
George Streisinger

SummaryRecessive lethal mutations and mutations at the gol-1 locus were induced in the zebrafish by exposure of mature sperm to the alkylating agent ethyl nitrosourea (ENU). Embryonic lethal phenotypes were recognized among the parthenogenetic progeny of mutagenized animals or among the progeny of daughters of mutagenized animals. Novel specific locus mutations were identified by the failure of mutagenized chromosomes to complement pre-existing mutant alleles at the gol-1 locus. Each mutagenized individual harboured approximately 10 embryonic lethal mutations in its germ line and about 1 in 500 mutagenized animals harboured a new mutation at the gol-1 locus. Three lines of evidence indicate that the majority of mutations that were recovered following treatment of mature sperm with ENU were probably point mutations. First, the soma and germ lines of mutagenized animals were mosaic, as expected following simple alkylation of sperm DNA. Second, mutations induced by ENU at the gol-1 locus affected pigmentation but not viability, unlike the majority of mutations induced at this locus with y-irradiation. Third, the ratio of specific locus: recessive lethal mutations induced by ENU was approximately 50-fold lower than the ratio observed following mutagenesis with y-rays. Comparison of the incidence with which embryonic recessive lethal mutations were induced with the incidence with which specific locus mutations arose indicates that there are greater than 5000 genes essential to the development and viability of the zebrafish embryo.


eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Karole N D'Orazio ◽  
Colin Chih-Chien Wu ◽  
Niladri Sinha ◽  
Raphael Loll-Krippleber ◽  
Grant W Brown ◽  
...  

Translation of problematic sequences in mRNAs leads to ribosome collisions that trigger a series of quality control events including ribosome rescue, degradation of the stalled nascent polypeptide, and targeting of the mRNA for decay (No Go Decay or NGD). Using a reverse genetic screen in yeast, we identify Cue2 as the conserved endonuclease that is recruited to stalled ribosomes to promote NGD. Ribosome profiling and biochemistry provide strong evidence that Cue2 cleaves mRNA within the A site of the colliding ribosome. We demonstrate that NGD primarily proceeds via Xrn1-mediated exonucleolytic decay and Cue2-mediated endonucleolytic decay normally constitutes a secondary decay pathway. Finally, we show that the Cue2-dependent pathway becomes a major contributor to NGD in cells depleted of factors required for the resolution of stalled ribosome complexes. Together these results provide insights into how multiple decay processes converge to process problematic mRNAs in eukaryotic cells.​


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