Cortical folding of the primate brain: an interdisciplinary examination of the genetic architecture, modularity, and evolvability of a significant neurological trait in pedigreed baboons (Genus Papio), pp. 651–665
Elizabeth G. Atkinson, Jeffrey Rogers, Michael C. Mahaney, Laura A. Cox, and James M. Cheverud
Folding of the brain cortex allows for improved neural processing power by increasing cortical surface area for the allocation of neurons. Using a large pedigreed population of ∼1000 Papio baboons, Atkinson et al. address critical questions about the genetic architecture of primate brain folding, the interplay between genetics, brain anatomy, development, patterns of cortical-cortical connectivity, and the potential for future evolution of cortex folding traits. The authors also map variation in these traits to specific genomic regions.
The chromatin and transcriptional landscape of native Saccharomyces cerevisiae telomeres and subtelomeric domains, pp. 505–521
Aisha Ellahi, Deborah M. Thurtle, and Jasper Rine
How and why are genes placed near telomeres silenced? Early studies showed that yeast genes near telomeres are silenced in a Sir- protein-dependent manner. However, these studies inserted reporter genes next to truncated, rather than natural, telomeres. Ellahi et al. combined ChIP-Seq of Sir proteins with RNA-Seq of wild type and sir mutants, and found that, surprisingly, most subtelomeric genes were expressed. Only 6% of subtelomeric genes were silenced in a Sir- protein-dependent manner. While this work provides independent validation of yeast telomere position effects, it also illuminates the mosaic nature of heterochromatin at telomeres and the sparse distribution of genes whose expression is affected by it.
Adaptation, clonal interference, and frequency-dependent interactions in a long-term evolution experiment with Escherichia coli, pp. 619–631
Rohan Maddamsetti, Richard E. Lenski, and Jeffrey E. Barrick
Maddamsetti et al. reconstructed the dynamics of 42 mutations over 20,000 generations of bacterial evolution. They show that cohorts of multiple beneficial mutations typically accumulated in a lineage before it was able to complete a selective sweep. In one striking case, two bacterial types with different sets of mutations coexisted for thousands of generations. This diversity was reinforced by frequency-dependent ecological interactions, but eventually collapsed after further evolution drove one type extinct.
Allelic imbalance is a prevalent and tissue-specific feature of the mouse transcriptome, pp. 537–549
Stefan F Pinter, David Colognori, Brian J. Beliveau, Ruslan I. Sadreyev, Bernhard Payer, Eda Yildirim, Chao-ting Wu, and Jeannie T. Lee
It is generally assumed that both alleles of a gene are equally expressed, although examples of allelic imbalance due to epigenetic phenomena are known. Pinter et al. measured allele-specific gene expression in hybrid offspring from genetically distinct mice, revealing allelic imbalance in one-fifth of all expressed genes. Genetic differences most likely account for the majority of this phenomenon, but surprisingly some of these genes are also monoallelic in inbred strains.
Efficient CRISPR/Cas9-mediated genome editing in mice by zygote electroporation of nuclease, pp. 423–430
Wenning Qin, Stephanie L. Dion, Peter M. Kutny, Yingfan Zhang, Albert W. Cheng, Nathaniel L. Jillette, Ankit Malhotra, Aron M. Geurts, Yi-Guang Chen, and Haoyi Wang
Multiplex conditional mutagenesis using transgenic expression of Cas9 and sgRNAs, pp. 431–441
Linlin Yin, Lisette A. Maddison, Mingyu Li, Nergis Kara, Matthew C. LaFave, Gaurav K. Varshney, Shawn M. Burgess, James G. Patton, and Wenbiao Chen
Two important extensions of CRISPR mutagenesis in vertebrates are reported this month. Qin et al. describe the Zygote Electroporation of Nuclease (ZEN) method, which improves the throughput of CRISPR applications in mice by avoiding the bottleneck of manual injection of CRISPR/Cas9 components. Yin et al. report a CRISPR system for multiplex conditional mutagenesis of zebrafish in one generation, allowing spatial and temporal control of gene inactivation.
Reconstructing past admixture processes from local genomic ancestry using wavelet transformation, pp. 469–481
Jean Sanderson, Herawati Sudoyo, Tatiana M. Karafet, Michael F. Hammer, and Murray P. Cox
Admixture between long-separated populations is a defining feature of the genomes of many species. As admixed genomes recombine, they produce a mosaic chromosome structure that contains information about when and how the two populations interacted. Sanderson et al. describe a new wavelet-based method to reconstruct these admixture processes. The authors show that their method performs well by applying it to simulated genetic data and human genome-wide SNP data from Indonesia. The method is released as the R package adwave.
Allele sharing and evidence for sexuality in a mitochondrial clade of bdelloid rotifers, pp. 581–590
Ana Signorovitch, Jae Hur, Eugene Gladyshev, and Matthew Meselson
The view that sexual reproduction is essential for long-term evolutionary success in eukaryotes is challenged by the apparent asexuality of the bdelloid rotifers, invertebrates of ancient origin. Signorovitch et al. demonstrate that members of a mitochondrial clade of bdelloids collected in the wild show a striking pattern of allele sharing consistent with sexual reproduction and with an unusual type of meiosis, in which segregation occurs without requiring homologous chromosome pairs.
Massively parallel functional analysis of BRCA1 RING domain variants, pp. 413–422
Lea M. Starita, David L. Young, Muhtadi Islam, Jacob O. Kitzman, Justin Gullingsrud, Ronald J. Hause, Douglas M. Fowler, Jeffrey D. Parvin, Jay Shendure, and Stanley Fields
Genetic tests often reveal missense mutations that are classified as Variants of Uncertain Significance (VUS), a result that is difficult for patients to interpret. Understanding how missense substitutions affect the function of the BRCA1 protein is of vital importance as more women undergo testing of this gene. Starita et al. show that the disease relevant cellular activity of BRCA1 variants can be accurately predicted on a large scale using results from massively parallel functional assays.
This Month in the American Journal of Human Genetics
Jump from pre-mutation to pathologic expansion in C9orf72, Am. J. Hum. Gent. 96(6)
Zhengrui Xi, PhD, Marka van Blitterswijk, Ming Zhang, PhD, Philip McGoldrick, Jesse R. McLean, Yana Yunusova, Erin Knock, Danielle Moreno, Christine Sato, Paul M. McKeever, Raphael Schneider, Julia Keith, Nicolae Petrescu, Paul Fraser, Maria Carmela Tartaglia, Matthew C. Baker, Neill R. Graff-Radford, Kevin B. Boylan, Dennis W. Dickson, Ian R. Mackenzie, Rosa Rademakers, Janice Robertson, Lorne Zinman, and Ekaterina Rogaeva
The expansion of the C9orf72 repeat is the most frequent variation associated with amyotrophic lateral sclerosis and frontotemporal lobar degeneration. Some studies have proposed that the expansion has arisen once in human history. However, in this study, Xi et al. report a family in which an allele expanded dramatically during the parent-offspring transmission. Although the lower limit for the number of expansions is suggested to be 30 repeats, the unaffected father harbored a 70-repeat expansion that was differentially methylated and expressed compared to his childrens’ pathogenic expansion of ∼1750-repeats. This observation is consistent with other diseases characterized by expanded repeats where small, nonpathogenic expansions can act as “pre-mutations.”
In CBE — Life Sciences Education (LSE)
Scientific teaching: defining a taxonomy of observable practices, CBE-Life Sci. Educ. vol. 14, ar9; 1–12
Brian A. Couch, Tanya L. Brown, Tyler J. Schelpat, Mark J. Graham, and Jennifer K. Knight
The need to redesign undergraduate science education has been the topic of many national conversations and reports in recent decades. Scientific Teaching (ST) has gained prominence as a pedagogical approach that would strive to answer the call for change. The goal of ST is to involve students in investigation and develop evidence to support the use of classroom methodologies, thereby reflecting the scientific process. Couch et al. have developed a taxonomy of observable ST practices that matches specific pedagogical goals to general approaches and provides supporting practices for each. This taxonomy is a useful resource for those looking to improve courses, document professional practices, discuss pedagogical approaches with colleagues, or embark on further studies of teaching and learning in science.
- Copyright © 2015 by the Genetics Society of America