Sunday, April 01, 2012


The genetics of Caenorhabditis elegans.

  
Genetics, Vol. 77, No. 1. (1 May 1974), pp. 71-94

This paper is recommended by Marty Chalfie (Columbia University), who writes:
The Brenner paper is a classic; when does someone have an opportunity to outline the genetics of an entire organism. It is also a terrific paper to go over basis genetic ideas. nearly all the variation affecting gene expression resides.his


Because it's brief, I'm going to quote the entire abstract from this classic:


Methods are described for the isolation, complementation and mapping of mutants of Caenorhabditis elegans, a small free-living nematode worm. About 300 EMS-induced mutants affecting behavior and morphology have been characterized and about one hundred genes have been defined. Mutations in 77 of these alter the movement of the animal. Estimates of the induced mutation frequency of both the visible mutants and X chromosome lethals suggests that, just as in Drosophila, the genetic units in C. elegans are large.




Functional enhancers at the gene-poor 8q24 cancer-linked locus


Functional enhancers at the gene-poor 8q24 cancer-linked locus.

PLoS genetics, Vol. 5, No. 8. (14 August 2009), e1000597, doi:10.1371/journal.pgen.1000597
This paper is recommended by Diane Robins (University of Michigan), who writes that this paper

"is the first functional analysis of a SNP in a gene desert that proves to be a variation in a FOX binding site making it a better androgen-responsive long-range enhancer for myc.  Follow-up paper shows interaction over 500 kb.."

Selection at linked sites shapes heritable phenotypic variation in C. elegans


Selection at linked sites shapes heritable phenotypic variation in C. elegans.

  
Science (New York, N.Y.), Vol. 330, No. 6002. (15 October 2010), pp. 372-376, doi:10.1126/science.1194208




This paper is recommended by Eric Haag (University of Maryland), who writes:

This paper is a real gem of interdisciplinary genetics thinking. Its key insight is that how natural selection impacts gene expression is highly subject to the overall frequency and chromosomal distribution of recombination (to the point of outweighing the biological processes affected).   Rockman shows that in mostly selfing nematodes like C. elegans, the central 50% of each autosome more or less acts like a "supergene" that harbors very little variation affecting gene expression genome-wide.  In contrast, the terminal 1/4 on either side is where nearly all the variation affecting gene expression resides. The available evidence suggests this occurs because selective sweeps wipe out the variation over much of the central domain of each automosome.

Competition between ADAR and RNAi pathways for an extensive class of RNA targets


Competition between ADAR and RNAi pathways for an extensive class of RNA targets.

  
Nature structural & molecular biology, Vol. 18, No. 10. (11 October 2011), pp. 1094-1101, doi:10.1038/nsmb.2129

This paper is recommended by Antony Jose (University of Maryland), who writes:

This work is a particularly elegant illustration of the powerful combination of computational methods with biochemical isolation of RNA from different genetic backgrounds. The discovery of numerous sites genome-wide where the transcribed RNA is edited by ADAR is noteworthy.


Saturday, March 24, 2012

Genome sequence, comparative analysis and haplotype structure of the domestic dog

I use this paper in my graduate genetics course because it is the third complete mammalian genome. Being the third genome allowed the first application of a range of comparative methods, revealing several aspects of mammalian genome structure for the first time.  The paper illustrates the methods of comparative genomics, and the application of population genetics to genomics and vice versa

Functions of the nonsense-mediated mRNA decay pathway in Drosophila development.

I use this this paper in my graduate genetics course to illustrate techniques for analysis of gene expression in Drosophila.  It's also a very nice example of serendipity, whereby mutations in a set of genes for a fundamental process (nonsense-mediated decay) were discovered while looking for something else entirely.  

SCNM1, a putative RNA splicing factor that modifies disease severity in mice

I use this paper in my graduate genetics course.  It describes the use of inbred strains to map and molecularly identify genes and illustrates a case of strain-specific phenotypes and genetic interactions.  It simultaneously illustrates the power of working with inbred strains and the caveat that phentypes can be strain-specific.

Novel and expanded roles for MAPK signaling in Arabidopsis stomatal cell fate revealed by cell type-specific manipulations


Novel and expanded roles for MAPK signaling in Arabidopsis stomatal cell fate revealed by cell type-specific manipulations.

The Plant cell, Vol. 21, No. 11. (November 2009), pp. 3506-3517, doi:10.1105/tpc.109.070110
I use this paper in my graduate genetics course. It describes a genetic analysis of stomatal cell fate using epistasis analysis. The paper illustrates epistasis analysis, methods for ectopic expression (in this case, cell type-specific expression of constitutively active and dominant negative alleles of kinases) and a bit of plant biology.

A DNA integrity network in the yeast Saccharomyces cerevisiae

I use this paper in my graduate genetics course.  It describes a global screen for synthetic defects involving DNA integrity, which reveals a network of 16 functional modules.  The paper illustrates screens based on genetic interactions (in this case, synthetic lethality or fitness defects) and the systems biology used to evaluate the results of such a screen.  It also illustrates the use of Saccharomyces cerevisiae as a model system.

A whole-genome RNAi Screen for C. elegans miRNA pathway genes


A whole-genome RNAi Screen for C. elegans miRNA pathway genes.

Current biology : CB, Vol. 17, No. 23. (4 December 2007), pp. 2013-2022, doi:10.1016/j.cub.2007.10.058

I use this paper in my graduate genetics course. It describes a whole-genome screen of C. elegans using RNA interference, provides an example of whole-genome parallel reverse genetic screens, and illustrates both the microRNA biosynthesis pathway and a bit of C. elegans biology.