Journal of Genetics and Genomics

Osteoporosis: A Silent Disease with Complex Genetic Contribution

Maryam Mafi Golchin, Laleh Heidari, Seyyed Mohammad Hossein Ghaderian, Haleh Akhavan-Niaki

2016, 43(2): 49-61. doi: 10.1016/j.jgg.2015.12.001

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Abstract:
Osteoporosis is the most common multifactorial metabolic bone disorder worldwide with a strong genetic component. In this review, the evidence for a genetic contribution to osteoporosis and related phenotypes is summarized alongside with methods used to identify osteoporosis susceptibility genes. The key biological pathways involved in the skeleton and bone development are discussed with a particular focus on master genes clustered in these pathways and their mode of action. Furthermore, the most studied single nucleotide polymorphisms (SNPs) analyzed for their importance as genetic markers of the disease are presented. New data generated by next-generation sequencing in conjunction with extensive meta-analyses should contribute to a better understanding of the genetic basis of osteoporosis and related phenotype variability. These data could be ultimately used for identifying at-risk patients for disease prevention by both controlling environmental factors and providing possible therapeutic targets.

Recent Progress in CRISPR/Cas9 Technology

Yue Mei, Yan Wang, Huiqian Chen, Zhong Sheng Sun, Xing-Da Ju

2016, 43(2): 63-75. doi: 10.1016/j.jgg.2016.01.001

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Abstract:
The clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system, a simple and efficient tool for genome editing, has experienced rapid progress in its technology and applicability in the past two years. Here, we review the recent advances in CRISPR/Cas9 technology and the ways that have been adopted to expand our capacity for precise genome manipulation. First, we introduce the mechanism of CRISPR/Cas9, including its biochemical and structural implications. Second, we highlight the latest improvements in the CRISPR/Cas9 system, especially Cas9 protein modifications for customization. Third, we review its current applications, in which the versatile CRISPR/Cas9 system was employed to edit the genome, epigenome, or RNA of various organisms. Although CRISPR/Cas9 allows convenient genome editing accompanied by many benefits, we should not ignore the significant ethical and biosafety concerns that it raises. Finally, we discuss the prospective applications and challenges of several promising techniques adapted from CRISPR/Cas9.

Dynamin Regulates Autophagy by Modulating Lysosomal Function

Xuefei Fang, Jia Zhou, Wei Liu, Xiuying Duan, Upasana Gala, Hector Sandoval, Manish Jaiswal, Chao Tong

2016, 43(2): 77-86. doi: 10.1016/j.jgg.2015.10.005

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Abstract:
Autophagy is a central lysosomal degradation pathway required for maintaining cellular homeostasis and its dysfunction is associated with numerous human diseases. To identify players in autophagy, we tested ∼1200 chemically induced mutations on the X chromosome in Drosophila fat body clones and discovered that shibire (shi) plays an essential role in starvation-induced autophagy. shi encodes a dynamin protein required for fission of clathrin-coated vesicles from the plasma membrane during endocytosis. We showed that Shi is dispensable for autophagy initiation and autophagosome–lysosome fusion, but required for lysosomal/autolysosomal acidification. We also showed that other endocytic core machinery components like clathrin and AP2 play similar but not identical roles in regulating autophagy and lysosomal function as dynamin. Previous studies suggested that dynamin directly regulates autophagosome formation and autophagic lysosome reformation (ALR) through its excision activity. Here, we provide evidence that dynamin also regulates autophagy indirectly by regulating lysosomal function.

Genetic Components of Heterosis for Seedling Traits in an Elite Rice Hybrid Analyzed Using an Immortalized F2 Population

Dan Zhu, Gang Zhou, Caiguo Xu, Qifa Zhang

2016, 43(2): 87-97. doi: 10.1016/j.jgg.2016.01.002

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Abstract:
Utilization of heterosis has greatly contributed to rice productivity in China and many Asian countries. Superior hybrids usually show heterosis at two stages: canopy development at vegetative stage and panicle development at reproductive stage resulting in heterosis in yield. Although the genetic basis of heterosis in rice has been extensively investigated, all the previous studies focused on yield traits at maturity stage. In this study, we analyzed the genetic basis of heterosis at seedling stage making use of an “immortalized F₂” population composed of 105 hybrids produced by intercrossing recombinant inbred lines (RILs) from a cross between Zhenshan 97 and Minghui 63, the parents of Shanyou 63, which is an elite hybrid widely grown in China. Eight seedling traits, seedling height, tiller number, leaf number, root number, maximum root length, root dry weight, shoot dry weight and total dry weight, were investigated using hydroponic culture. We analyzed single-locus and digenic genetic effects at the whole genome level using an ultrahigh-density SNP bin map obtained by population re-sequencing. The analysis revealed large numbers of heterotic effects for seedling traits including dominance, overdominance and digenic dominance (epistasis) in both positive and negative directions. Overdominance effects were prevalent for all the traits, and digenic dominance effects also accounted for a large portion of the genetic effects. The results suggested that cumulative small advantages of the single-locus effects and two-locus interactions, most of which could not be detected statistically, could explain the genetic basis of seedling heterosis of the F₁ hybrid.

Overexpression of Jak1 Activating Mutants in Hepatocytes Is Insufficient to Generate Hepatocellular Carcinoma in Zebrafish

Yue Yuan, Jian Zhang, Qin Zhou

2016, 43(2): 99-102. doi: 10.1016/j.jgg.2015.11.003

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Abstract:

Targeted Mutagenesis of Duplicated Genes in Caenorhabditis elegans Using CRISPR-Cas9

Suhong Xu, Zhiping Wang, Kyung Won Kim, Yishi Jin, Andrew D. Chisholm

2016, 43(2): 103-106. doi: 10.1016/j.jgg.2015.11.004

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Abstract:

2016 Vol. 43, No. 2