Journal of Genetics and Genomics

Zebrafish as a Model for Human Ciliopathies

Zhu Song, Xiaoli Zhang, Shuo Jia, Pamela C. Yelick, Chengtian Zhao

2016, 43(3): 107-120. doi: 10.1016/j.jgg.2016.02.001

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Abstract:
Cilia, microtubule-based structures found on the surface of almost all vertebrate cells, play an array of diverse biological functions. Abnormal ciliary axonemal structure and function can result in a class of genetic disorders that are collectively termed ciliopathies. Model organisms, including Chlamydomonas reinhardtii and Caenorhabditis elegans have been widely used to study the complex genetic basis of ciliopathies. Here, we review the advantages of the zebrafish as a vertebrate model for human ciliopathies. We summarize the features of zebrafish cilia, and the major findings and contributions of the zebrafish model in recent studies of human ciliopathies. We also discuss the new genome editing approaches being efficiently used in zebrafish, and the exciting prospects of these approaches in modeling human ciliopathies.

Spectrum of Cytogenomic Abnormalities Revealed by Array Comparative Genomic Hybridization on Products of Conception Culture Failure and Normal Karyotype Samples

Qinghua Zhou, Shen-Yin Wu, Katherine Amato, Autumn DiAdamo, Peining Li

2016, 43(3): 121-131. doi: 10.1016/j.jgg.2016.02.002

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Abstract:
Approximately 30% of pregnancies after implantation end up in spontaneous abortions, and 50% of them are caused by chromosomal abnormalities. However, the spectrum of genomic copy number variants (CNVs) in products of conception (POC) and the underlying gene-dosage-sensitive mechanisms causing spontaneous abortions remain largely unknown. In this study, array comparative genomic hybridization (aCGH) analysis was performed as a salvage procedure for 128 POC culture failure (POC-CF) samples and as a supplemental procedure for 106 POC normal karyotype (POC-NK) samples. Chromosomal abnormalities were detected in 10% of POC-CF and pathogenic CNVs were detected in 3.9% of POC-CF and 5.7% of POC-NK samples. Compiled results from this study and relevant case series through a literature review demonstrated an abnormality detection rate (ADR) of 35% for chromosomal abnormalities in POC-CF samples, 3.7% for pathogenic CNVs in POC-CF samples, and 4.6% for pathogenic CNVs in POC-NK samples. Ingenuity Pathway Analysis (IPA) was performed on the genes from pathogenic CNVs found in POC samples. The denoted primary gene networks suggested that apoptosis and cell proliferation pathways are involved in miscarriage. In summary, a similar spectrum of cytogenomic abnormalities was observed in POC culture success and POC-CF samples. A threshold effect correlating the number of dosage-sensitive genes in a chromosome with the observed frequency of autosomal trisomy is proposed. A rationalized approach using firstly fluorescencein situ hybridization (FISH) testing with probes of chromosomes X/Y/18, 13/21, and 15/16/22 for common aneuploidies and polyploidies and secondly aCGH for other cytogenomic abnormalities is recommended for POC-CF samples.

Comprehensive Analysis of Pan-African Mitochondrial DNA Variation Provides New Insights into Continental Variation and Demography

María Cerezo, Leonor Gusmão, Viktor Černý, Nabeel Uddin, Denise Syndercombe-Court, Alberto Gómez-Carballa, Tanja Göbel, Peter M. Schneider, Antonio Salas

2016, 43(3): 133-143. doi: 10.1016/j.jgg.2015.09.005

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Abstract:
Africa is the cradle of all human beings, and although it has been the focus of a number of genetic studies, there are many questions that remain unresolved. We have performed one of the largest and most comprehensive meta-analyses of mitochondrial DNA (mtDNA) lineages carried out in the African continent to date. We generated high-throughput mtDNA single nucleotide polymorphism (SNP) data (230 SNPs) from 2024 Africans, where more than 500 of them were additionally genotyped for the control region. These data were analyzed together with over 12,700 control region profiles collected from the literature, representing more than 300 population samples from Africa. Insights into the African homeland of humans are discussed. Phylogeographic patterns for the African continent are shown at a high phylogeographic resolution as well as at the population and regional levels. The deepest branch of the mtDNA tree, haplogroup L0, shows the highest sub-haplogroup diversity in Southeast and East Africa, suggesting this region as the homeland for modern humans. Several demographic estimates point to the coast as a facilitator of human migration in Africa, but the data indicate complex patterns, perhaps mirroring the effect of recent continental-scaled demographic events in re-shaping African mtDNA variability.

Involvement of a Putative Bipartite Transit Peptide in Targeting Rice Pheophorbide a Oxygenase into Chloroplasts for Chlorophyll Degradation during Leaf Senescence

Qingjun Xie, Yan Liang, Jian Zhang, Huakun Zheng, Guojun Dong, Qian Qian, Jianru Zuo

2016, 43(3): 145-154. doi: 10.1016/j.jgg.2015.09.012

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Abstract:
Leaf senescence is one of the major factors contributing to the productivity and the grain quality in crops. The regulatory mechanism of leaf senescence remains largely unknown. Here, we report the identification and characterization of a rice (eas1) mutant, which displayed an early leaf senescence phenotype, accompanying by dwarfism and reduced tiller number, eventually leading to the reduction of grain yield. Map-based cloning revealed that the nuclear gene EAS1 encodes a pheophorbide a oxygenase (PaO), a key enzyme for chlorophyll breakdown. A highly conserved Thr residue of PaO was mutated into Ile in the eas1 mutant. Phylogenetic analysis indicates that PaO is an evolutionarily conserved protein, and EAS1 is 68% identical to the Arabidopsis ACCERLERATED CELL DEATH (ACD1) protein. Unlike ACD1 that contains a single transit peptide, EAS1 contains two putative transit peptides at its N-terminus, which are essential for its functionality, suggesting that targeting of EAS1 to the chloroplast is likely mediated by a putative bipartite transit peptide. Consistently, only a short version of EAS1 lacking the first putative transit peptide, but not the full-length EAS1, was capable of rescuing theArabidopsis acd1 mutant phenotype. These results suggest that rice EAS1 represents a functional PaO, which is involved in chlorophyll degradation and may utilize a unique mechanism for its import into the chloroplast.

A New Next-Generation Sequencing-Based Assay for Concurrent Preimplantation Genetic Diagnosis of Charcot-Marie-Tooth Disease Type 1A and Aneuploidy Screening

Baoheng Gui, Pu Yang, Zhongyuan Yao, Yanping Li, Donge Liu, Nenghui Liu, Sijia Lu, Desheng Liang, Lingqian Wu

2016, 43(3): 155-159. doi: 10.1016/j.jgg.2016.01.003

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Abstract:

Efficient Derivation of Human Induced Pluripotent Stem Cells with a c-Myc-Free Non-Integrating Episomal Vector

Juan Wang, Qi Gu, Jie Hao, Donghui Bai, Liu Wang, Zhonghua Liu, Qi Zhou

2016, 43(3): 161-164. doi: 10.1016/j.jgg.2016.01.004

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Abstract:

2016 Vol. 43, No. 3