ISSUE HIGHLIGHTS Free

Characterizing race/ethnicity and genetic ancestry for 100,000 subjects in the genetic epidemiology research on adult health and aging (GERA) cohort, pp. 1285–1295

Yambazi Banda, Mark N. Kvale, Thomas J. Hoffmann, Stephanie E. Hesselson, Dilrini Ranatunga, Hua Tang, Chiara Sabatti, Lisa A. Croen, Brad P. Dispensa, Mary Henderson, Carlos Iribarren, Eric Jorgenson, Lawrence H. Kushi, Dana Ludwig, Diane Olberg, Charles P. Quesenberry Jr., Sarah Rowell, Marianne Sadler; Lori C. Sakoda, Stanley Sciortino, Ling Shen, David Smethurst, Carol P. Somkin, Stephen K. Van Den Eeden, Lawrence Walter, Rachel A. Whitmer, Pui-Yan Kwok, Catherine Schaefer, and Neil Risch

Banda et al. characterized how self-reported race/ethnicity/nationality relates to the genetic structure of 103,006 participants in the Northern California Kaiser Permanente multi-ethnic Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort. By self-report the cohort is 80.8% white and 19.2% minority. Patterns of genetic ancestry were strongly related to self-reported race/ethnicity. Comparison of parent-child pairs revealed a trend towards increasing exogamy (marriage outside the social group). The increasing presence of individuals endorsing multiple race/ethnicity categories creates interesting challenges and future opportunities for genetic epidemiologic studies.

Selection on optimal haploid value increases genetic gain and preserves more genetic diversity relative to genomic selection, pp. 1341–1348

Hans D. Daetwyler, Matthew J. Hayden, German C. Spangenberg, and Ben J. Hayes

Many breeding programs now routinely use genomic selection and doubled haploids to accelerate genetic improvement. Daetwyler et al. propose an extension to genomic selection called Optimal Haploid Selection that predicts the best doubled haploid that can be produced from a segregating plant. They show that selection based on Optimal Haploid Value increases genetic gain and, importantly, preserves more genetic diversity in breeding populations when compared to genomic selection.

Streamlined genome engineering with a self-excising drug selection cassette, pp. 1035–1049

Daniel J. Dickinson, Ariel M. Pani, Jennifer K. Heppert, Christopher D. Higgins, and Bob Goldstein

Dickinson et al. describe a new selection strategy for genome engineering in Caenorhabditis elegans that requires less manual labor than existing approaches and has a high first-try success rate. The approach is based on a self-excising drug selection cassette that enables scar-free insertion into the genome in a wild-type background, without PCR screening. It can also be used to produce a transcriptional reporter, loss-of-function allele, and protein fusion simultaneously in a single injection step. The basic principles of the approach should apply to other systems.

Stable patterns of CENH3 occupancy through maize lineages containing genetically similar centromeres, pp. 1105–1116

Jonathan I. Gent, Kai Wang, Jiming Jiang, and R. Kelly Dawe

The specification and inheritance of centromeres is enigmatic because they are not defined by sequence-specific binding proteins. Gent et al. hypothesized that, like other epigenetic phenomena, the position of centromeres would change over time and vary stochastically. However, no variation in centromere position was revealed by examination of eleven maize lineages spanning approximately fifteen generations. Position of the centromeric histone variant cenH3/CENP-A showed strong biases against genes and towards specific repetitive elements, suggesting that DNA elements contribute to centromere stability.

Nitric oxide synthase regulates growth coordination during Drosophila melanogaster imaginal disc regeneration, pp. 1219–1228

Jacob S. Jaszczak, Jacob B. Wolpe, Anh Q. Dao, and Adrian Halme

How growth is coordinated between distinct organs to maintain consistent size and proportion is unclear. Jaszczak et al. describe a pathway for growth coordination between regenerating and undamaged tissues in Drosophila larvae. They demonstrate that a regeneration signal, Dilp8, limits growth in undamaged tissues by activating nitric oxide synthase (NOS) in the prothoracic gland. NOS activation then reduces production of the steroid hormone ecdysone, which is necessary to maintain the growth of undamaged imaginal discs.

Catch me if you can: adaptation from standing genetic variation to a moving phenotypic optimum, pp. 1255–1274

Sebastian Matuszewski, Joachim Hermisson, and Michael Kopp

Matuszewski et al. propose an analytical framework that addresses which alleles from the multitude of standing genetic variants contribute to adaptation, and how their effect-size distribution differs from that of de novo mutations. They find that adaptation from standing genetic variation proceeds via many small-effect fixations and just a few large ones. They also show that populations that adapt from standing genetic variation only have a higher potential for adaptation and population persistence if environmental change is fast rather than slow.

Selective advantages of a parasexual cycle for the yeast Candida albicans, pp. 1117–1132

Ningxin Zhang, Beatrice B. Magee, Paul T. Magee, Barbara R. Holland, Ely Rodrigues, Ann R. Holmes, Richard D. Cannon, and Jan Schmid

Sex is costly, and abandoning sex in favor of clonal reproduction can be advantageous over short evolutionary time scales. The pathogenic yeast Candida albicans mates extremely rarely via a cumbersome process. To determine whether this mating process is biologically significant, Zhang et al. investigated whether mating genes are under selection and whether mating could generate progeny with fitness advantages in novel environments. The results show that mating ability is under selection because mating can ameliorate genetic defects and offers occasional benefits for adaptation.

Reconstruction of genome ancestry blocks in multiparental populations, pp. 1073–1087

Chaozhi Zheng, Martin P. Boer, and Fred A. van Eeuwijk

Zheng et al. present a general method for reconstructing genome-wide ancestry blocks bit by bit (RABBIT) from single nucleotide polymorphism data. This framework is more robust and accurate than some commonly used methods. It can be applied to a wide range of mapping populations, including the mouse Collaborative Cross (CC), diversity outcross (DO), advanced intercross lines (AIL), Arabidopsis multiparent recombinant inbred lines (AMPRIL), and the Multiparent Advanced Generation Inter-Cross (MAGIC).

This Month’s Perspectives

Ellsworth C. Dougherty: a pioneer in the selection of Caenorhabditis elegans as a model organism, pp. 991–1002

Howard Ferris and W. F. Hieb

The foresight and passion of Ellsworth Dougherty (1926-1965) cast him as a pioneer in the selection of Caenorhabditis elegans as a model organism. In a brief but intense career, Dougherty worked on the genetics and culture of nematodes, classification of the Protista, and instituted terminologies for systematics, cell structure, and culture media. Major advances in neurobiology and molecular biology, with important applications in medicine, have resulted from the insights of this talented but largely-forgotten scientist.

This Month in the American Journal of Human Genetics

THOC2 mutations implicate mRNA export pathway in X-linked intellectual disability, Am. J. Hum. Gent. 97(2)

Raman Kumar, Mark A Corbett, Bregje WM van Bon, Joshua A Woenig, Lloyd Weir, Evelyn Douglas, Kathryn L Friend, Alison Gardner, Marie Shaw, Lachlan A Jolly, Chuan Tan, Matthew F Hunter, Anna Hackett, Michael Field, Elizabeth E Palmer, Melanie Leffler, Carolyn Rogers, Jackie Boyle, Melanie Bienek, Corinna Jensen, Griet Van Buggenhout, Hilde Van Esch, Katrin Hoffmann, Martine Raynaud, Huiying Zhao, Robin Reed, Hao Hu, Stefan A Haas, Eric Haan, Vera M Kalscheuer, and Jozef Gecz

Proper neuronal development requires the coordination of numerous cellular pathways; such complexity renders this developmental process exquisitely sensitive to genetic perturbations. In their search for mutations that underlie X-linked intellectual disability (XLID), Kumar et al. uncover variants in THOC2, a gene whose protein product is a component of the TREX mRNA export complex. Proper spatiotemporal control of mRNA export is required for protein synthesis as well as the maintenance of cellular homeostasis. The identified variants are predicted to affect mRNA binding, and further characterization should shed light on disease mechanism as well provide insight into as normal TREX function.

In CBE — Life Sciences Education (LSE)

A model of how different biology experts explain molecular and cellular mechanisms, CBE-Life Sci. Educ. vol.14, 2; ar 20

Caleb M. Trujillo, Trevor R. Anderson, and Nancy J. Pelaez

Using the whiteboard in your office or lab to explain the molecular and cellular mechanisms underlying your research is teaching at its most engaging. It meets the challenge put forth in Vision and Change for the teaching of science to reflect the practice of science. But how do we convert this style into a pedagogical approach for our classrooms? Through examining how experts explain molecular and cellular mechanisms, Trujillo et al. have developed the MACH model which incorporates four elements found in all explanations studied: Methods of research, Analogies, social or biological Context, and How the mechanism works. The authors provide guidelines to help educators utilize the MACH model in a classroom setting.