Advanced Genetics

Abstract Strong selection has resulted in substantial morphological and behavioral diversity across modern dog breeds, which makes dogs interesting model animals to study the underlying genetic architecture of these traits. However, results from between‐breed analyses may confound selection signatures for behavior and morphological features that were coselected during breed development. In this study, we assess population genetic differences in a unique resource of dogs of the same breed but with systematic behavioral selection in only one population. We exploit these different breeding backgrounds to identify signatures of recent selection. Selection signatures within populations were found on chromosomes 4 and 19, with the strongest signals in behavior‐related genes. Regions showing strong signals of divergent selection were located on chromosomes 1, 24, and 32, and include candidate genes for both physical features and behavior. Some of the selection signatures appear to be driven by loci associated with coat color (Chr 24; ASIP ) and length (Chr 32; FGF5 ), while others showed evidence of association with behavior. Our findings suggest that signatures of selection within dog breeds have been driven by selection for morphology and behavior. Furthermore, we demonstrate that combining selection scans with association analyses is effective for dissecting the traits under selection.

Juliane Friedrich

Andrea Talenti

Per Arvelius

Erling Strandberg

Marie J. Haskell

Pamela Wiener

Unravelling selection signatures in a single dog breed suggests recent selection for morphological and behavioral traits

揭示单一犬种中的选择信号提示近期对形态和行为特征的选择

Abstract Hearing loss is the most common sensory defect in humans, affecting normal communication. In most cases, hearing loss is a multifactorial disorder caused by both genetic and environmental factors, but single‐gene mutations can lead to syndromic or non‐syndromic hearing loss. Monoallelic variants in ACTG1 , coding for gamma (γ)‐actin, are associated with classical Baraitser‐Winter Syndrome type 2 (BRWS2, nonsyndromic deafness, and a variety of clinical presentations not fitting the original BRWS2 description or nonsyndromic deafness. Here two unrelated patients with ACTG1 variants are reported, having severe hearing loss as a common phenotype but with different clinical presentations, supporting the extreme variability of ACTG1 ‐related disorders.

Maria T. Bernardi

Memoona Ramzan

Laura Calderon

Franco Salvatore

Maria Agustina De Rosa

Stephanie Bivona

Romina Armando

Natalia Vazquez

Maria Esnaola Azcoiti

Marcelo A. Marti

Claudia Arberas

Maria Gabriela Ropelato

Silvina Olha

Byron L. Lam

Fred F. Telischi

Mustafa Tekin

Katherina Walz

Extreme Phenotypic Variability of <i>ACTG1</i>‐Related Disorders in Hearing Loss

<i>ACTG1</i>相关听力损失疾病的极端表型变异性

Cancer cells produce heterogeneous extracellular vesicles (EVs) as mediators of intercellular communication. This study focuses on a novel method to image EV subtypes and their biodistribution in vivo. A red-shifted bioluminescence resonance energy transfer (BRET) EV reporter is developed, called PalmReNL, which allows for highly sensitive EV tracking in vitro and in vivo. PalmReNL enables the authors to study the common surface molecules across EV subtypes that determine EV organotropism and their functional differences in cancer progression. Regardless of injection routes, whether retro-orbital or intraperitoneal, PalmReNL positive EVs, isolated from murine mammary carcinoma cells, localized to the lungs. The early appearance of metastatic foci in the lungs of mammary tumor-bearing mice following multiple intraperitoneal injections of the medium and large EV (m/lEV)-enriched fraction derived from mammary carcinoma cells is demonstrated. In addition, the results presented here show that tumor cell-derived m/lEVs act on distant tissues through upregulating LC3 expression within the lung.

Gloria I. Perez

David Broadbent

Ahmed A. Zarea

Benedikt Dolgikh

Matthew P. Bernard

Alicia Withrow

Amelia McGill

Victoria Toomajian

Lukose K. Thampy

Jack Harkema

Joel R. Walker

Thomas A. Kirkland

Michael H. Bachmann

Jens Schmidt

Masamitsu Kanada

In Vitro and In Vivo Analysis of Extracellular Vesicle‐Mediated Metastasis Using a Bright, Red‐Shifted Bioluminescent Reporter Protein

体外和体内分析利用明亮、红移生物发光报告蛋白的细胞外囊泡介导的转移

Trauma is ubiquitous, but only a subset of those who experience trauma will develop posttraumatic stress disorder (PTSD). In this review, it is argued that to determine who is at risk of developing PTSD, it is critical to examine the genetic etiology of the disorder and individual trauma profiles of those who are susceptible. First, the state of current PTSD genetic research is described, with a particular focus on studies that present evidence for trauma type specificity, or for differential genetic etiology according to gender or race. Next, approaches that leverage non-traditional phenotyping approaches are reviewed to identify PTSD-associated variants and biology, and the relative advantages and limitations inherent in these studies are reflected on. Finally, it is discussed how trauma might influence the heritability of PTSD, through type, risk factors, genetics, and associations with PTSD symptomology.

Shelby Marchese

Laura M. Huckins

Trauma Matters: Integrating Genetic and Environmental Components of PTSD

创伤问题：整合创伤后应激障碍的遗传与环境因素

Traditionally, the group 1 intron of the T4 td gene is used to generate a foreign circular sequence. However, the T4 system has been shown to be fairly inefficient in expressing circular RNA (circRNA). Here, a new method is developed to express circular sequences with high circularization efficiency to strengthen the confidence for future circRNA functional studies. CircRNA expression plasmids, constructed with different lengths derived from the actin intron (15-nt, 30-nt, 60-nt, 100-nt, 180-nt) and T4 intron, are introduced into human and mouse cell lines 293T and B16. Junction detection and sequencing are used to determine successful circularization of introns and their expression efficiencies. An actin intron with a medium length (60-nt-100-nt) shows significantly increased efficiency of circularization, whereas intron-100-nt shows the best efficiency in most conditions. RNA pull-down assays are designed to precipitate the splicing factors that are bound to the introns and intron/exon junction. The precipitated proteins are analyzed by mass spectrometry (MS), aiming to identify the possible underlying mechanism behind the high circularization efficiency. This expression system has been validated using different circRNAs, and such method shows potential in contributing to the expanding field of circRNA studies.

Feiya Li

Juanjuan Lyu

Yang Yang

Qiwei Yang

Cristian Santos

Burton B. Yang

An Improved Model for Circular RNA Overexpression: Using the Actin Intron Reveals High Circularization Efficiency

一种改进的环状RNA过表达模型：利用肌动蛋白内含子揭示高环化效率

The VISTA enhancer database is a valuable resource for evaluating predicted enhancers in humans and mice. In addition to thousands of validated positive regions (VPRs) in the human and mouse genomes, the database also contains similar numbers of validated negative regions (VNRs). It is previously shown that the VPRs are on average half as long as predicted overlapping enhancers that are highly conserved and hypothesize that the VPRs may be truncated forms of long bona fide enhancers. Here, it is shown that like the VPRs, the VNRs also are under strong evolutionary constraints and overlap predicted enhancers in the genomes. The VNRs are also on average half as long as predicted overlapping enhancers that are highly conserved. Moreover, the VNRs and the VPRs display similar cell/tissue-specific modification patterns of key epigenetic marks of active enhancers. Furthermore, the VNRs and the VPRs show similar impact score spectra of in silico mutagenesis. These highly similar properties between the VPRs and the VNRs suggest that like the VPRs, the VNRs may also be truncated forms of long bona fide enhancers.

Pengyu Ni

Siwen Wu

Zhengchang Su

Validated Negative Regions (VNRs) in the VISTA Database might be Truncated Forms of Bona Fide Enhancers

VISTA数据库中的验证负区（VNRs）可能是真实增强子的截断形式

The co-occurrence of sensorineural hearing loss and male infertility has been reported in several instances, suggesting potential shared genetic underpinnings. One such example is the contiguous gene deletion of

Jeffrey Justin Margret

Chandru Jayasankaran

Pavithra Amritkumar

Hela Azaiez

C. R. Srikumari Srisailapathy

Unraveling the Genetic Basis of Combined Deafness and Male Infertility Phenotypes through High‐Throughput Sequencing in a Unique Cohort from South India

揭示南印度独特人群中通过高通量测序联合耳聋与男性不育表型的遗传基础

Abstract The social movement to reduce reliance on pesticides and synthesized fertilizers and the growing global demand for sustainable food supplies require the development of eco‐friendly and sustainable agricultural practices. In line, plant growth‐promoting bacteria (PGPB) can participate in creating innovative agroecological systems. While the effectiveness of PGPB is highly influenced by abiotic conditions and microbe–microbe interactions, beneficial plant–PGPB interactions can also highly depend on both host and PGPB genotype. Here, the state of the art on the extent of natural genetic variation of plant–PGPB interactions and the underlying genetic architecture, in particular in Arabidopsis thaliana is reviewed. Extensive natural plant genetic variation in response to PGPB is associated with a polygenic architecture and genetic pathways rarely mentioned as being involved in the response to PGPB. To date, natural genetic variation within PGPB is little explored, which may in turn allow the identification of new genetic pathways underlying benefits to plants. Accordingly, several avenues to better understand the genomic and molecular landscape of plant–PGPB interactions are introduced. Finally, the need for establishing thorough functional studies of candidate genes underlying Quantitative Trait Loci and estimating the extent of genotype‐by‐genotype‐by‐environment interactions within the context of realistic (agro‐)ecological conditions is advocated.

Rémi Duflos

Fabienne Vailleau

Fabrice Roux

Toward Ecologically Relevant Genetics of Interactions Between Host Plants and Plant Growth‐Promoting Bacteria

面向宿主植物与植物促生细菌相互作用的生态相关遗传学研究

Ultraviolet (UV) light is the most pervasive environmental mutagen and the primary cause of skin cancer. Genome sequencing of melanomas and other skin cancers has revealed that the vast majority of somatic mutations in these tumors are cytosine-to-thymine (C>T) substitutions in dipyrimidine sequences, which, together with tandem CC>TT substitutions, comprise the canonical UV mutation "signature". These mutation classes are caused by DNA damage directly induced by UV absorption, namely cyclobutane pyrimidine dimers (CPDs) or 6-4 pyrimidine-pyrimidone photoproducts (6-4PP), which form between neighboring pyrimidine bases. However, many of the key driver mutations in melanoma do not fit this mutation signature, but instead are caused by T>A, T>C, C>A, or AC>TT substitutions, frequently occurring in non-dipyrimidine sequence contexts. This article describes recent studies indicating that UV light causes a more diverse spectrum of mutations than previously appreciated, including many of the mutation classes observed in melanoma driver mutations. Potential mechanisms for these diverse mutation signatures are discussed, including UV-induced pyrimidine-purine photoproducts and indirect DNA damage induced by UVA light. Finally, the article reviews recent findings indicating that human DNA polymerase eta normally suppresses these non-canonical UV mutation classes, which can potentially explain why canonical C>T substitutions predominate in human skin cancers.

Publication Information	Publisher: John Wiley & Sons Inc.，Publishing cycle: ，Journal Type: journal，Open Access Journals: Yes
Basic data	Year of publication: 2021，Proportion of original research papers: ，Self Citation Rate:， Gold OA Rate:
Journal Fees	$2500Details
Average review cycle	14 weeks

Advanced Genetics

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