Genetics, Vol. 182, August 2009, Copyright © 2009

ISSUE HIGHLIGHTS

A new standard genetic map for the laboratory mouse, pp. 1335–1344

Allison Cox, Cheryl L. Ackert-Bicknell, Beth L. Dumont, Yueming Ding, Jordana Tzenova Bell, Gudrun A. Brockmann, Jon E. Wergedal, Carol Bult, Beverly Paigen, Jonathan Flint, Shirng-Wern Tsaih, Gary A. Churchill and Karl W. Broman

Genetic maps continue to be relevant. They remain a critical tool for mapping genes underlying complex traits, and they provide insights into fundamental processes of recombination. This group of investigators produces an improved genetic map of the laboratory mouse genome that is fully integrated with the physical map of the genome. In the process of creating the new map, they correct numerous errors that had accumulated in the mouse map. They demonstrate the impact of these improvements by remapping several historical QTLs.

Genetic modifiers of dFMR1 encode RNA granule components in Drosophila, pp. 1051–1060

Anne-Marie J. Cziko, Cathal T. McCann, Iris C. Howlett, Scott A. Barbee, Rebecca P. Duncan, Rene Luedemann, Daniela Zarnescu, Konrad E. Zinsmaier, Roy R. Parker and Mani Ramaswami

Fragile-X Mental Retardation Protein (FMRP) is a translational repressor that in neurons probably prevents translation of synaptic RNAs until a threshold of activation is reached. FMRP is also believed to be required for microRNA-mediated translational repression. This article describes a genetic screen that reveals likely new components of the fragile-X pathway that, like FMRP, can modify dendritic structure. The authors come to the unexpected conclusion that FMRP is not essential for microRNA function.

High-throughput multiplex sequencing to discover copy number variants in Drosophila, pp. 935–941

Bryce Daines, Hui Wang, Yumei Li, Yi Han, Richard Gibbs and Rui Chen

This article presents the use of high-throughput DNA sequencing for identifying copy number variation, an approach that promises to become the method of choice for such studies. The authors demonstrate that low sequence coverage is sufficient for identifying and mapping large deletions at kilobase resolution. They show how multiplexing is a good alternative to microarrays because of its greater resolution at a comparable (and rapidly declining) cost.

Domains of heterochromatin protein 1 required for Drosophila melanogaster heterochromatin spreading, pp. 967–977

Karrie A. Hines, Diane E. Cryderman, Kaitlin M. Flannery, Hongbo Yang, Michael W. Vitalini, Tulle Hazelrigg, Craig A. Mizzen and Lori L. Wallrath

Heterochromatin, which makes up a significant fraction of the genome in nearly all eukaryotes, can spread along the chromosome and silence gene expression. Studying the mechanism of heterochromatin spreading has been challenging due to the repetitive DNA sequences that underlie heterochromatin. These investigators employ the lac repressor to establish heterochromatin domains amenable for analysis of spreading. They identify domains of heterochromatin protein 1 required for spreading, and unexpectedly reveal multiple mechanisms of spreading. Taken together, their findings provide new insights into the mechanisms of transcriptional control by chromatin.

Measuring the rates of spontaneous mutation from deep and large-scale polymorphism data, pp. 1219–1232

Philipp W. Messer

Mutations are the foundation of genetic diversity, yet we remain uncertain about their rates and patterns. This is because new mutations are difficult to assess experimentally, since they occur at extremely low rates in individuals. Indirect estimates of mutation rates from levels of divergence or heterozygosity suffer from unknown selective and demographic biases and disregard deleterious mutations. The author demonstrates how unbiased mutation rate estimates can be obtained from polymorphism data gathered from deep sequencing projects. This promises to facilitate the assessment of several long-standing problems of evolutionary biology.

Modeling multiallelic selection using a Moran model, pp. 1141–1157

Christina A. Muirhead and John Wakeley

Mechanisms of natural selection are of great interest to evolutionary biologists, but available population genetics models are often discouragingly oversimplified. This article presents a new mathematical method of modeling complex multiallelic selection that greatly simplifies the task of analyzing novel modes of selection and is much less reliant on simplifying assumptions than previous models based on diffusion approximations to Wright-Fisher reproduction.

Contribution of gene amplification to evolution of increased antibiotic resistance in Salmonella typhimurium, pp. 1183–1195

Song Sun, Otto G. Berg, John R. Roth and Dan I. Andersson

These investigators study evolution of resistance to a β-lactam antibiotic. They expose Salmonella typhimurium carrying a β-lactamase-encoding gene to increasing concentrations of the antibiotic. The predominant response is amplification of the β-lactamase gene. Some lineages subsequently acquire mutations that reduce expression of porins involved in drug uptake, whereupon selection for the β-lactamase gene amplification relaxes and its copy number becomes reduced. These findings suggest that gene amplification facilitates the acquisition of stable adaptive mutations by increasing the number of selected target genes in the population.

Global analysis of allele-specific expression in Arabidopsis thaliana, pp. 943–954

Xu Zhang and Justin O. Borevitz

The level of gene expression is a complex trait controlled by cis- and trans-acting genetic factors. Dissection of these two sources of genetic variation promises to shed light on how gene regulatory networks evolved. These investigators find that genes subject to these two different classes of variation are distinct in their local sequence polymorphisms, associated epigenetic marks, and gene expression specificity.

This Month in Genetics Research

Evaluation of risk prediction updates from commercial genome-wide scans, Genet. Med. 11: 588–594

Cecile Jansenns

Is "personalized medicine" ready for prime time? Several companies currently offer online genetic tests to predict an individual's risk of common diseases, but those predictions may be premature, because susceptibility genes for common diseases are still being discovered, potentially making predictions of risk outdated. The authors of this article investigate the extent to which updating of risk predictions results in reclassification of individuals from below- to above-average disease risk, or vice versa. They conclude that updating risk factors may produce contradictory information about an individual's risk status over time, which is undesirable if lifestyle and nutritional recommendations vary accordingly.

Massively parallel sequencing: The next big thing in genetic medicine, Am. J. Hum. Genet. 85: 142–154

Tracy Tucker, Marco Marra and Jan M. Friedman

"Next generation" DNA sequencing technologies are rapidly changing how we identify mutations. The first people to man the barricades of this technological revolution have been experimentalists (e.g., GENETICS 182: 25–32, and articles in this issue by Messer and by Daines et al.), but our applied and clinical comrades are quickly taking up the cause. This article in our sister publication describes how application of massively parallel DNA sequencing in the clinic promises to provide a way to determine the etiology of many diseases by screening the genomes of thousands of people for pathogenic mutations and genomic signatures of novel infectious agents. The authors lay out the significant practical and ethical challenges to implementation of this transformative technology.


Related articles in Genetics:

Genetic Modifiers of dFMR1 Encode RNA Granule Components in Drosophila
Anne-Marie J. Cziko, Cathal T. McCann, Iris C. Howlett, Scott A. Barbee, Rebecca P. Duncan, Rene Luedemann, Daniela Zarnescu, Konrad E. Zinsmaier, Roy R. Parker, and Mani Ramaswami
Genetics 2009 182: 1051-1060. [Abstract] [Full Text]  

Modeling Multiallelic Selection Using a Moran Model
Christina A. Muirhead and John Wakeley
Genetics 2009 182: 1141-1157. [Abstract] [Full Text]  

Contribution of Gene Amplification to Evolution of Increased Antibiotic Resistance in Salmonella typhimurium
Song Sun, Otto G. Berg, John R. Roth, and Dan I. Andersson
Genetics 2009 182: 1183-1195. [Abstract] [Full Text]  

Measuring the Rates of Spontaneous Mutation From Deep and Large-Scale Polymorphism Data
Philipp W. Messer
Genetics 2009 182: 1219-1232. [Abstract] [Full Text]  

A New Standard Genetic Map for the Laboratory Mouse
Allison Cox, Cheryl L. Ackert-Bicknell, Beth L. Dumont, Yueming Ding, Jordana Tzenova Bell, Gudrun A. Brockmann, Jon E. Wergedal, Carol Bult, Beverly Paigen, Jonathan Flint, Shirng-Wern Tsaih, Gary A. Churchill, and Karl W. Broman
Genetics 2009 182: 1335-1344. [Abstract] [Full Text]  

High-Throughput Multiplex Sequencing to Discover Copy Number Variants in Drosophila
Bryce Daines, Hui Wang, Yumei Li, Yi Han, Richard Gibbs, and Rui Chen
Genetics 2009 182: 935-941. [Abstract] [Full Text]  

Global Analysis of Allele-Specific Expression in Arabidopsis thaliana
Xu Zhang and Justin O. Borevitz
Genetics 2009 182: 943-954. [Abstract] [Full Text]  

Domains of Heterochromatin Protein 1 Required for Drosophila melanogaster Heterochromatin Spreading
Karrie A. Hines, Diane E. Cryderman, Kaitlin M. Flannery, Hongbo Yang, Michael W. Vitalini, Tulle Hazelrigg, Craig A. Mizzen, and Lori L. Wallrath
Genetics 2009 182: 967-977. [Abstract] [Full Text]