(3α,5β,9β,10α,13α,15R)-3-(β-D-Glucopyranosyloxy)-15-hydroxypimar-8(14)-en-16-yl acetate/β-D-Glucopyranoside, (2R,4aS,4bR,7S,10aS)-7-[(1R)-2-(acetyloxy)-1-hydroxyethyl]-1,2,3,4,4a,4b,5,6,7,9,10,10a-dodecahydro-1,1,4a,7-tetramethyl-2-phenanthrenyl
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Recent studies have demonstrated the power of deep re-sequencing of the whole genome or exome in understanding cancer genomes. However, targeted capture of selected genomic whole gene-body regions, rather than the whole exome, have several advantages: 1) the genes can be selected based on biology or a hypothesis; 2) mutations in promoter and intronic regions, which have important regulatory roles, can be investigated; and 3) less expensive than whole genome or whole exome sequencing. Therefore, we designed custom high-density oligonucleotide microarrays (NimbleGen Inc.) to capture approximately 1.7 Mb target regions comprising the genomic regions of 28 genes related to colorectal cancer including genes belonging to the WNT signaling pathway, as well as important transcription factors or colon-specific genes that are over expressed in colorectal cancer (CRC). The 1.7 Mb targeted regions were sequenced with a coverage ranged from 32× to 45× for the 28 genes. We identified a total of 2342 sequence variations in the CRC and corresponding adjacent normal tissues. Among them, 738 were novel sequence variations based on comparisons with the SNP database (dbSNP135). We validated 56 of 66 SNPs in a separate cohort of 30 CRC tissues using Sequenom MassARRAY iPLEX Platform, suggesting a validation rate of at least 85% (56/66). We found 15 missense mutations among the exonic variations, 21 synonymous SNPs that were predicted to change the exonic splicing motifs, 31 UTR SNPs that were predicted to occur at the transcription factor binding sites, 20 intronic SNPs located near the splicing sites, 43 SNPs in conserved transcription factor binding sites and 32 in CpG islands. Finally, we determined that rs3106189, localized to the 5′ UTR of antigen presenting tapasin binding protein (TAPBP), and rs1052918, localized to the 3′ UTR of transcription factor 3 (TCF3), were associated with overall survival of CRC patients.
Targeted Re-Sequencing Identified rs3106189 at the 5′ UTR of TAPBP and rs1052918 at the 3′ UTR of TCF3 to Be Associated with the Overall Survival of Colorectal Cancer Patients
Jiaofang Shao, 1 , 2 , 3 Xiaoyan Lou, 3 Jun Wang, 3 Jing Zhang, 3 Chen Chen, 3 Dasong Hua, 3 Fan Mo, 3 Xu Han, 3 Shu Zheng, 1 , * and Biaoyang Lin 1 , 2 , 3 , 4 , 5 , * Hiromu Suzuki, Editor
Copy number variations (CNVs) confer significant effects on genetic innovation and phenotypic variation. Previous CNV studies in swine seldom focused on in-depth characterization of global CNVs.
Using whole-genome assembly comparison (WGAC) and whole-genome shotgun sequence detection (WSSD) approaches by next generation sequencing (NGS), we probed formation signatures of both segmental duplications (SDs) and individualized CNVs in an integrated fashion, building the finest resolution CNV and SD maps of pigs so far. We obtained copy number estimates of all protein-coding genes with copy number variation carried by individuals, and further confirmed two genes with high copy numbers in Meishan pigs through an enlarged population. We determined genome-wide CNV hotspots, which were significantly enriched in SD regions, suggesting evolution of CNV hotspots may be affected by ancestral SDs. Through systematically enrichment analyses based on simulations and bioinformatics analyses, we revealed CNV-related genes undergo a different selective constraint from those CNV-unrelated regions, and CNVs may be associated with or affect pig health and production performance under recent selection.
Our studies lay out one way for characterization of CNVs in the pig genome, provide insight into the pig genome variation and prompt CNV mechanisms studies when using pigs as biomedical models for human diseases.
Electronic supplementary material
The online version of this article (doi:10.1186/1471-2164-15-593) contains supplementary material, which is available to authorized users.
Copy number variations (CNVs), Segmental duplications (SDs), Next generation sequencing (NGS), Pigs
Global copy number analyses by next generation sequencing provide insight into pig genome variation
Jicai Jiang,corresponding author Jiying Wang,corresponding author Haifei Wang, Yan Zhang, Huimin Kang, Xiaotian Feng, Jiafu Wang, Zongjun Yin, Wenbin Bao, Qin Zhang, and Jian-Feng Liucorresponding author
Background: In recent years, the study of birth intervals has been a main determinant of the levels of fertility in the populations, as it is associated with rates of fertility and population growth.
Objective: The purpose of this study was to firstly apply survival analysis for modeling of first birth interval and secondly to explore its determinants.
Materials and Methods: In a cross sectional study, the fertility history of 858 women was collected in rural areas of Shiraz (southern Iran) in 2008. We used the survival analysis such as cox regression and alternative parametric models to evaluate the prognostic factors of first birth interval.
Results: Among the explanatory variables of interest, age at marriage, level of women’s education, and menstrual status had highly significant effects on the duration of birth interval after marriage (p<0.01). Conclusion: It is concluded that the suitable parametric models would be a useful tool for fitting to first birth interval, the fact that has been less paid attention to in researches.
First birth interval, Survival analysis, Parametric models
Prognostic factors of first birth interval using the parametric survival models
Zahra Shayan, Ph.D.,1 Seyyed Mohammad Taghi Ayatollahi, Ph.D.,1 Najaf Zare, Ph.D.,2 and Fariba Moradi, M.D., M.P.H.3