Journal of Genetics and Genomics

Recent progress in the genetics of generalized vitiligo

Richard A. Spritz

2011, 38(7): 271-278. doi: 10.1016/j.jgg.2011.05.005

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Abstract:
Vitiligo is an acquired disease characterized principally by patchy depigmentation of skin and overlying hair. Generalized vitiligo (GV), the predominant form of the disorder, results from autoimmune loss of melanocytes from affected regions. GV is a “complex trait”, inherited in a non-Mendelian polygenic, multifactorial manner. GV is epidemiologically associated with other autoimmune diseases, both in GV patients and in their close relatives, suggesting that shared genes underlie susceptibility to this group of diseases. Early candidate gene association studies yielded a few successes, such as PTPN22, but most such reports now appear to be false-positives. Subsequent genomewide linkage studies identified NLRP1 and XBP1, apparent true GV susceptibility genes involved in immune regulation, and recent genome-wide association studies (GWAS) of GV in Caucasian and Chinese populations have yielded a large number of additional validated GV susceptibility genes. Together, these genes highlight biological systems and pathways that reach from the immune cells to the melanocyte, and provide insights into both disease pathogenesis and potential new targets for both treatment and even prevention of GV and other autoimmune diseases in genetically susceptible individuals.

Evolutionary rewiring and reprogramming of bacterial transcription regulation

Li Wang, Fang-Fang Wang, Wei Qian

2011, 38(7): 279-288. doi: 10.1016/j.jgg.2011.06.001

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Abstract:
Rewiring and reprogramming of transcriptional regulation took place during bacterial speciation. The mechanistic alterations among transcription factors, cis-regulatory elements and target genes confer bacteria novel ability to adapt to stochastic environmental changes. This process is critical to their survival, especially for bacterial pathogens subjected to accelerated evolution. In the past two decades, the investigators not only completed the sequences of numerous bacterial genomes, but also made great progress in understanding the molecular basis of evolution. Here we briefly reviewed the current knowledge on the mechanistic changes among orthologous, paralogous and xenogenic regulatory circuits, which were caused by genetic recombinations such as gene duplication, horizontal gene transfer, transposable elements and different genetic contexts. We also discussed the potential impact of this area on theoretical and applied studies of microbes.

Establishment of novel embryonic stem (ES) cell lines from OG2/rtTA blastocysts

Hui Yao, Yonghua Jiang, Yu Zhang, Wenqiang Liu, Bo Huang, Xiaodong Wang, Shaorong Gao

2011, 38(7): 289-295. doi: 10.1016/j.jgg.2011.05.007

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Abstract:
Embryonic stem (ES) cells derived from the pre-implantation blastocyst-stage embryos have been widely used to investigate the molecular events determining pluripotency and cell lineage differentiation. As the first discovered ES-specific transcription factor, Oct4 has been considered as the core pluripotency factor of ES cells. In the present study, we successfully established seven ES lines from the blastocysts collected from female OG2 (Oct4-GFP transgenic) mice, which have been crossed with male rtTA transgenic mice. The pluripotency of the ES cell lines can be visualized by the expression of Oct4-GFP under fluorescent microscopy and germ-line transmission capability has been further confirmed. More importantly, the presence of rtTA could induce transgene’s expression with the help of doxycycline. Therefore, these ES cell lines provide an excellent tool to further discover novel factors affecting pluripotency and to investigate the molecular mechanism of reprogramming in defined transcription factors mediated nuclear reprogramming.

Increased complexity of gene structure and base composition in vertebrates

Ying Wu, Huizhong Yuan, Shengjun Tan, Jian-Qun Chen, Dacheng Tian, Haiwang Yang

2011, 38(7): 297-305. doi: 10.1016/j.jgg.2011.06.004

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Abstract:
How the structure and base composition of genes changed with the evolution of vertebrates remains a puzzling question. Here we analyzed 895 orthologous protein-coding genes in six multicellular animals: human, chicken, zebrafish, sea squirt, fruit fly, and worm. Our analyses reveal that many gene regions, particularly intron and 3′ UTR, gradually expanded throughout the evolution of vertebrates from their invertebrate ancestors, and that the number of exons per gene increased. Studies based on all protein-coding genes in each genome provide consistent results. We also find that GC-content increased in many gene regions (especially 5′ UTR) in the evolution of endotherms, except in coding-exons. Analysis of individual genomes shows that 3′ UTR demonstrated stronger length and GC-content correlation with intron than 5′ UTR, and gene with large intron in all six species demonstrated relatively similar GC-content. Our data indicates a great increase in complexity in vertebrate genes and we propose that the requirement for morphological and functional changes is probably the driving force behind the evolution of structure and base composition complexity in multicellular animal genes.

The alkaline tolerance in Arabidopsis requires stabilizing microfilament partially through inactivation of PKS5 kinase

Juntao Liu, Yan Guo

2011, 38(7): 307-313. doi: 10.1016/j.jgg.2011.05.006

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Abstract:
High soil pH is harmful to plant growth and development. The organization and dynamics of microfilament (MF) cytoskeleton play important roles in the plant anti-alkaline process. In the previous study, we determined that alkaline stress induces a signal that triggers MF dynamics-dependent root growth. In this study we identified that PKS5 kinase involves in this regulatory process to facilitate the signal to reach the downstream target MF. Under pH 8.3 treatment, the depolymerization of MF was faster in pks5-4 (PKS5 kinase constitutively activated) than that in wild-type plants. The inhibition of wild-type, pks5-1, and pks5-4 root growth by pH 8.3 was correlated to their MF depolymerization rate. When the plants were treated with phalloidin to stabilize MF, the high pH sensitive phenotype of pks5-4 can be partially rescued. When the plants were treated with a kinase inhibitor Staurosporine, the MF depolymerization rate in pks5-4 was similar as that in wild-type under pH 8.3 treatment and the sensitivity of root growth was also rescued. However, when the plants were treated with LaCl₃, a calcium channel blocker, the root growth sensitivity of pks5-4 under pH 8.3 was rescued but MF depolymerization was even faster than that of plants without LaCl₃ treatment. These results suggest that the PKS5 involves in external high pH signal mediated MF depolymerization, and that may be independent of calcium signal.

Use of methylation filtration and C0t fractionation for analysis of genome composition and comparative genomics in bread wheat

Rajib Bandopadhyay, Sachin Rustgi, Rajat Kanti Chaudhuri, Paramjit Khurana, Jitendra Paul Khurana, Akhilesh Kumar Tyagi, Harindra Singh Balyan, Andreas Houben, Pushpendra Kumar Gupta

2011, 38(7): 315-325. doi: 10.1016/j.jgg.2011.06.003

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Abstract:
We investigated the compositional and structural differences in sequences derived from different fractions of wheat genomic DNA obtained using methylation filtration and C₀t fractionation. Comparative analysis of these sequences revealed large compositional and structural variations in terms of GC content, different structural elements including repeat sequences (e.g., transposable elements and simple sequence repeats), protein coding genes, and non-coding RNA genes. A correlation between methylation status [determined on the basis of selective inclusion/exclusion in methylation-filtered (MF) library] of different repeat elements and expression level was observed. The expression levels were determined by comparing MF sequences with expressed sequence tags (ESTs) available in the public domain. Only a limited overlap among MF, high C₀t (HC), and ESTs was observed, suggesting that these sequences may largely either represent the low-copy non-transcribed sequences or include genes with low expression levels. Thus, these results indicated a need to study MF and HC sequences along with ESTs to fully appreciate complexity of wheat gene space.

2011 Vol. 38, No. 7