Genetics, Vol. 178, March 2008, Copyright © 2008

ISSUE HIGHLIGHTS

The contribution of social effects to heritable variation in finishing traits of domestic pigs (Sus scrofa), pp. 1559–1570

R. Bergsma, E. Kanis, E. F. Knol and P. Bijma

Social interactions among individuals are ubiquitous in natural as well as in domestic populations. These interactions are a key factor in the evolutionary success of species and influence the design of breeding schemes in agriculture. How much do social effects contribute to heritable variance in trait values? This article estimates the direct and social genetic variance in growth rate, feed intake, back fat thickness, and muscle depth in a population of 14,032 domestic pigs with known pedigree. Social effects were found to contribute the vast majority of heritable variance in growth rate and feed intake, but not in back fat thickness or muscle depth. These results suggest that genetic improvement in agriculture can be significantly advanced by redirecting breeding schemes in a way that captures heritable variance due to social effects.

Identification of novel genes that modify phenotypes induced by Alzheimer's β-amyloid overexpression in Drosophila, pp. 1457–1471

Weihuan Cao, Ho-Juhn Song, Tina Gangi, Anju Kelkar, Isha Antani, Dan Garza and Mary Konsolaki

It is not known why deposits of β-amyloid peptides cause Alzheimer's disease. Using Drosophila-expressing β-amyloid, the authors identify genes that mediate the effects of β-amyloid peptides. They discover that components of the secretory pathway, cholesterol homeostasis, and chromatin structure and function are involved in β-amyloid toxicity. Some of these components also mediate the toxicity of other neurodegenerative agents, suggesting the existence of common mechanisms of neurodegeneration.

A screen for modifiers of Hedgehog signaling in Drosophila melanogaster identifies swm and mts, pp. 1399–1413

David J. Casso, Songmei Liu, D. David Iwaki, Stacey K. Ogden and Thomas B. Kornberg

This article makes it clear that there is still much to learn about Hedgehog signaling, which is critical for development and has been implicated in human diseases, including many cancers. This article describes a screen for haploinsufficient modifiers of Hedgehog signaling, which turned up 26 chromosomal deficiencies that enhance or suppress signaling. Two genes—microtubule star and second mitotic wave missing—were found to be essential for normal developmental patterning, cell growth regulation, and cell polarity, suggesting that Hedgehog signaling integrates and regulates the outputs of these pathways.

Catalytic-site mutations in the MYST family histone acetyltransferase Esa1, pp. 1209–1220

Peter V. Decker, David Y. Yu, Masayoshi Iizuka, Qifeng Qiu and M. Mitchell Smith

Acetylation of histones is certainly important, but Esa1, the catalytic subunit of the NuA4 complex, is the only essential histone acetyltransferase in budding yeast. These investigators make the surprising discovery that changing residues in the Esa1 catalytic site eliminates enzyme activity but does not cause lethality. Could the essential role of Esa1 be to serve as a regulatory sensor of cofactor or substrate levels for the NuA4 complex?

Synergistic fitness interactions and a high frequency of beneficial changes among mutations accumulated under relaxed selection in Saccharomyces cerevisiae, pp. 1571–1578

W. Joseph Dickinson

Interactions among mutations that individually have small effects on fitness are important in evolution, as they affect the maintenance of sexual reproduction and recombination, the process of speciation, and the survival of small populations. However, relevant experimental results are limited, inconsistent, and controversial. This article reports the results of a mutation accumulation experiment with yeast that uses sensitive head-to-head competition experiments to measure relative fitness in a defined environment. Reinforcing synergistic interactions are evident. A surprising 25% of mutations with detectable fitness effects were beneficial.

Efficient control of population structure in model organism association mapping, pp. 1709–1723

Hyun Min Kang, Noah A. Zaitlen, Claire M. Wade, Andrew Kirby, David Heckerman, Mark J. Daly and Eleazar Eskin

Because the experiments can be controlled, in silico association mapping studies in inbred model organisms are potentially more powerful than association mapping in outbred human populations. But domestic and laboratory organisms often have complex population structure, which can inflate false positive rates. This article develops an efficient mixed-model association (EMMA) test that efficiently corrects for population structure in model organism association mapping studies. Application of EMMA to whole-genome association mapping of inbred mouse strains identified associated SNPs in previously identified QTL.

Gene network inference via structural equation modeling in genetical genomics experiments, pp. 1763–1776

Bing Liu, Alberto de la Fuente and Ina Hoeschele

This article develops the use of structural equation modeling (SEM) for gene network inference (GNI) in expression quantitative trait locus (eQTL) analysis. Using gene expression and DNA sequence information, the authors construct an initial network of causal regulatory relationships among genes and eQTL, which they call an encompassing directed network (EDN). A set of sparser networks is then found by searching within the EDN network space using SEM implemented for up to several hundred genes and eQTL.

An investigation of heterochromatin domains on the fourth chromosome of Drosophila melanogaster, pp. 1177–1191

Nicole C. Riddle, Wilson Leung, Karmella A. Haynes, Howard Granok, Jo Wuller and Sarah C. R. Elgin

The banded portion of Drosophila melanogaster chromosome 4 exhibits characteristics of euchromatin and heterochromatin. This domain contains a high percentage of repetitive elements, lacks recombination, and exhibits high levels of heterochromatic marks, but gene density is similar to euchromatic chromosome arms. This article describes two screens using a P-element reporter to look for heterochromatin target sites. The authors confirm that reporters within 10 kb of a 1360 element are usually packaged as heterochromatin; however, heterochromatin packaging occurs in regions lacking 1360. Analyses of sequences adjacent to reporters show no simple association between specific repeated elements and transgene expression phenotype. Rather than the presence of a particular sequence element, the data require that heterochromatin formation depends on a complex pattern of sequence organization, as well as nuclear localization.

Role of proliferating cell nuclear antigen interactions in the mismatch repair-dependent processing of mitotic and meiotic recombination intermediates in yeast, pp. 1221–1236

Jana E. Stone, Regan Gealy Ozbirn, Thomas D. Petes and Sue Jinks-Robertson

Mismatch repair (MMR) is critical for eukaryotic genome stability. It repairs DNA replication errors, removes mismatches in recombination intermediates, and limits recombination between nonidentical sequences. The DNA polymerase processivity protein PCNA is required for efficient repair of replication errors, but its involvement in MMR during recombination has not been examined. Results reported in this article suggest that PCNA is required for repair of meiotic heteroduplex DNA, but plays little, if any, role in the antirecombination function of the mismatch machinery during recombination.

Adaptive functional divergence among triplicated {alpha}-globin genes in rodents, pp. 1623–1638

Jay F. Storz, Federico G. Hoffmann, Juan C. Opazo and Hideaki Moriyama

The products of duplicated (paralogous) genes usually accumulate amino acid differences. Is this due to a relaxation of purifying selection or to a positive selection that has steered the gene products toward new or modified tasks? These authors attribute accelerated rates of amino acid substitution in the independently derived {alpha}-globin paralogs of the Norway rat and the deer mouse to positive directional selection. In the deer mouse, a species that is able to sustain physiological function under conditions of chronic hypoxia at high altitude, the coexpression of distinct hemoglobin isoforms with graded oxygen affinities probably broadens the range of permissible arterial oxygen tensions.

Recruitment and dissociation of nonhomologous end joining proteins at a DNA double-strand break in Saccharomyces cerevisiae, pp. 1237–1249

Dongliang Wu, Leana M. Topper and Thomas E. Wilson

Nonhomologous end joining (NHEJ) is a DNA repair pathway critical for maintaining genome stability. This article provides a framework for understanding the NHEJ reaction in yeast by establishing the order binding and dissociation of the several proteins involved in NHEJ from double-strand breaks undergoing productive repair. Analysis of breaks that fail to be repaired reveals an active pathway of protein dissociation hypothesized to be an important part of the switch to homologous recombination.


Related articles in Genetics:

An Investigation of Heterochromatin Domains on the Fourth Chromosome of Drosophila melanogaster
Nicole C. Riddle, Wilson Leung, Karmella A. Haynes, Howard Granok, Jo Wuller, and Sarah C. R. Elgin
Genetics 2008 178: 1177-1191. [Abstract] [Full Text]  

Catalytic-Site Mutations in the MYST Family Histone Acetyltransferase Esa1
Peter V. Decker, David Y. Yu, Masayoshi Iizuka, Qifeng Qiu, and M. Mitchell Smith
Genetics 2008 178: 1209-1220. [Abstract] [Full Text]  

Role of Proliferating Cell Nuclear Antigen Interactions in the Mismatch Repair-Dependent Processing of Mitotic and Meiotic Recombination Intermediates in Yeast
Jana E. Stone, Regan Gealy Ozbirn, Thomas D. Petes, and Sue Jinks-Robertson
Genetics 2008 178: 1221-1236. [Abstract] [Full Text]  

Recruitment and Dissociation of Nonhomologous End Joining Proteins at a DNA Double-Strand Break in Saccharomyces cerevisiae
Dongliang Wu, Leana M. Topper, and Thomas E. Wilson
Genetics 2008 178: 1237-1249. [Abstract] [Full Text]  

A Screen for Modifiers of Hedgehog Signaling in Drosophila melanogaster Identifies swm and mts
David J. Casso, Songmei Liu, D. David Iwaki, Stacey K. Ogden, and Thomas B. Kornberg
Genetics 2008 178: 1399-1413. [Abstract] [Full Text]  

Identification of Novel Genes That Modify Phenotypes Induced by Alzheimer's β-Amyloid Overexpression in Drosophila
Weihuan Cao, Ho-Juhn Song, Tina Gangi, Anju Kelkar, Isha Antani, Dan Garza, and Mary Konsolaki
Genetics 2008 178: 1457-1471. [Abstract] [Full Text]  

The Contribution of Social Effects to Heritable Variation in Finishing Traits of Domestic Pigs (Sus scrofa)
R. Bergsma, E. Kanis, E. F. Knol, and P. Bijma
Genetics 2008 178: 1559-1570. [Abstract] [Full Text]  

Synergistic Fitness Interactions and a High Frequency of Beneficial Changes Among Mutations Accumulated Under Relaxed Selection in Saccharomyces cerevisiae
W. Joseph Dickinson
Genetics 2008 178: 1571-1578. [Abstract] [Full Text]  

Adaptive Functional Divergence Among Triplicated {alpha}-Globin Genes in Rodents
Jay F. Storz, Federico G. Hoffmann, Juan C. Opazo, and Hideaki Moriyama
Genetics 2008 178: 1623-1638. [Abstract] [Full Text]  

Efficient Control of Population Structure in Model Organism Association Mapping
Hyun Min Kang, Noah A. Zaitlen, Claire M. Wade, Andrew Kirby, David Heckerman, Mark J. Daly, and Eleazar Eskin
Genetics 2008 178: 1709-1723. [Abstract] [Full Text]  

Gene Network Inference via Structural Equation Modeling in Genetical Genomics Experiments
Bing Liu, Alberto de la Fuente, and Ina Hoeschele
Genetics 2008 178: 1763-1776. [Abstract] [Full Text]