Genomic analysis

Advances in genomic analysis include improved technology for DNA sequencing, routine use of DNA microarray technology for the analysis of gene expression profiles at the mRNA level and improved informatic tools to organize and analyze such data. At the same time, new developments in chip-based analysis of samples and the emergence of models of gene networks hold promise for the future of the 'Genomic Era'.     

Genomic alignment

As sequencing techniques become increasingly efficient, the average length of a sequence is bound to grow. Traditional sequence-comparison algorithms can either compare DNA or protein, but not a mixture, which is actually a common situation. Most obtained DNA sequences contain coding regions, and it is more reliable to compare the coding regions as protein than just as DNA.A heuristic algorithm is presented that can compare DNA with both coding and noncoding regions, but that also can compare multiple reading frames and determine which exons are homologous.A program, GenAl (Genomic Alignment), was developed that implements the algorithm. Its use is demonstrated on two retroviruses. Correspondence to: J. Hein     

基因组印记

根据孟德尔遗传定律,当一种性状从亲代传到子代,涉及这种性状的基因和染色体无论是来自父方或母方,传递所产生的表型效应都应该是完全相同的。但是这一普遍规律现已发现在哺乳动物某些组织和细胞中会出现例外．即控制某一表型的一对等位基因由于亲源不同而差异性表达,也就是说,机体只表达来自亲本一方的等位基因．而与其自身性别无关。这就称为基因组印记（genomic imprinting）。其中父（母）系等位基因不表达者,就称为父（母）系印记。它不遵循孟德尔遗传规律。     

Locally Epistatic Genomic Relationship Matrices for Genomic Association and Prediction

In plant and animal breeding studies a distinction is made between the genetic value (additive plus epistatic genetic effects) and the breeding value (additive genetic effects) of an individual since it is expected that some of the epistatic genetic effects will be lost due to recombination. In this article, we argue that the breeder can take advantage of the epistatic marker effects in regions of low recombination. The models introduced here aim to estimate local epistatic line heritability by using genetic map information and combining local additive and epistatic effects. To this end, we have used semiparametric mixed models with multiple local genomic relationship matrices with hierarchical designs. Elastic-net postprocessing was used to introduce sparsity. Our models produce good predictive performance along with useful explanatory information.     

Genomic imprinting.

In the last few years, the importance of genomic imprinting as a basic biological phenomenon has become clear. Work from different areas has demonstrated that parent-of-origin differences in phenotype occur on a regular basis. This article summarizes some of the recent advances made in this field.     

Including Dominance Effects in the Genomic BLUP Method for Genomic Evaluation

We evaluated the performance of GBLUP including dominance genetic effect (GBLUP-D) by estimating variances and predicting genetic merits in a computer simulation and 2 actual traits (T4 and T5) in pigs. In simulation data, GBLUP-D explained more than 50% of dominance genetic variance. Moreover, GBLUP-D yielded estimated total genetic effects over 1.2% more accurate than those yielded by GBLUP. In particular, when the dominance genetic variance was large, the accuracy could be substantially improved by increasing the number of markers. The dominance genetic variances in T4 and T5 accounted for 9.6% and 6.3% of the phenotypic variances, respectively. Estimates of such small dominance genetic variances contributed little to the improvement of the accuracies of estimated total genetic effects. In both simulation and pig data, there were nearly no differences in the estimates of additive genetic effects or their variance between GBLUP-D and GBLUP. Therefore, we conclude GBLUP-D is a feasible approach to improve genetic performance in crossbred populations with large dominance genetic variation and identify mating systems with good combining ability.     

Genomic Profiling of Oral Squamous Cell Carcinoma by Array-Based Comparative Genomic Hybridization

We designed a study to investigate genetic relationships between primary tumors of oral squamous cell carcinoma (OSCC) and their lymph node metastases, and to identify genomic copy number aberrations (CNAs) related to lymph node metastasis. For this purpose, we collected a total of 42 tumor samples from 25 patients and analyzed their genomic profiles by array-based comparative genomic hybridization. We then compared the genetic profiles of metastatic primary tumors (MPTs) with their paired lymph node metastases (LNMs), and also those of LNMs with non-metastatic primary tumors (NMPTs). Firstly, we found that although there were some distinctive differences in the patterns of genomic profiles between MPTs and their paired LNMs, the paired samples shared similar genomic aberration patterns in each case. Unsupervised hierarchical clustering analysis grouped together 12 of the 15 MPT-LNM pairs. Furthermore, similarity scores between paired samples were significantly higher than those between non-paired samples. These results suggested that MPTs and their paired LNMs are composed predominantly of genetically clonal tumor cells, while minor populations with different CNAs may also exist in metastatic OSCCs. Secondly, to identify CNAs related to lymph node metastasis, we compared CNAs between grouped samples of MPTs and LNMs, but were unable to find any CNAs that were more common in LNMs. Finally, we hypothesized that subpopulations carrying metastasis-related CNAs might be present in both the MPT and LNM. Accordingly, we compared CNAs between NMPTs and LNMs, and found that gains of 7p, 8q and 17q were more common in the latter than in the former, suggesting that these CNAs may be involved in lymph node metastasis of OSCC. In conclusion, our data suggest that in OSCCs showing metastasis, the primary and metastatic tumors share similar genomic profiles, and that cells in the primary tumor may tend to metastasize after acquiring metastasis-associated CNAs.     

基因组印迹调节

虽然大多数哺乳动物基因都是双座位表达,但是有一少部分基因发生印迹,只有父母双方基因中的一个实际表达,这种表观遗传过程迁涉到发育不同阶段基因的表达调节,十分复杂,原则上印迹基因在生殖细胞中必须用表观遗传标记顺式标记,这些标记能够通过细胞分裂进行保存,在成熟生物分化细胞中能够指导多基因单座位表达,在生殖细胞形成早期两个座位上的表达差别必须消除,以便在成熟生殖细胞中重新设置印迹,在该文中,概述了目前所知介导这些过程的分子机制。     

The Genomic Standards Consortium

A vast and rich body of information has grown up as a result of the world's enthusiasm for 'omics technologies. Finding ways to describe and make available this information that maximise its usefulness has become a major effort across the 'omics world. At the heart of this effort is the Genomic Standards Consortium (GSC), an open-membership organization that drives community-based standardization activities, Here we provide a short history of the GSC, provide an overview of its range of current activities, and make a call for the scientific community to join forces to improve the quality and quantity of contextual information about our public collections of genomes, metagenomes, and marker gene sequences.