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Human genome resequencing projects provide an unprecedented amount of data about single-nucleotide variations occurring in protein-coding regions and often leading to observable changes in the covalent structure of gene products. For many of these variations, links to Online Mendelian Inheritance in Man (OMIM) genetic diseases are available and are reported in many databases that are collecting human variation data such as Humsavar. However, the current knowledge on the molecular mechanisms that are leading to diseases is, in many cases, still limited. For understanding the complex mechanisms behind disease insurgence, the identification of putative models, when considering the protein structure and chemico-physical features of the variations, can be useful in many contexts, including early diagnosis and prognosis. In this study, we investigate the occurrence and distribution of human disease–related variations in the context of Pfam domains. The aim of this study is the identification and characterization of Pfam domains that are statistically more likely to be associated with disease-related variations. The study takes into consideration 2,513 human protein sequences with 22,763 disease-related variations. We describe patterns of disease-related variation types in biunivocal relation with Pfam domains, which are likely to be possible markers for linking Pfam domains to OMIM diseases. Furthermore, we take advantage of the specific association between disease-related variation types and Pfam domains for clustering diseases according to the Human Disease Ontology, and we establish a relation among variation types, Pfam domains, and disease classes. We find that Pfam models are specific markers of patterns of variation types and that they can serve to bridge genes, diseases, and disease classes. Data are available as Supplementary Material for 1,670 Pfam models, including 22,763 disease-related variations associated to 3,257 OMIM diseases.

主动脉弓分支血管发生变异是常见的现象，常见的变异类型有：牛型弓、椎动脉起自主动 脉弓、右锁骨下动脉迷行，其他类型的变异较为罕见。主动脉弓上血管的变异来源于胚胎时期原始咽 弓动脉的发育异常，但影响变异产生的具体机制尚不明确。虽然主动脉弓分支血管变异通常为无症状 的，但其部分与先天性心血管疾病及遗传性疾病的发生存在明显相关性。由于变异的发生，外科手 术或血管内治疗操作的难度和危险性会明显增高。本文基于国内外关于主动脉弓分支血管变异研究 的现状，针对变异的类型、胚胎学发生机制及其对临床工作产生的影响等方面进行综述。 Abstract: The variations of branches of aortic arch are very common, and the common variation types include the bovine arch, the left vertebral artery originating from aortic arch and the aberrant right subclavian artery, and the other types are rare. The vascular variations of super-aortic arch arise from the abnormal development of primordial pharyngeal arch arteries during embryonic period, but the mechanism of vessel variations remains unclear. Although most of these variations are asymptomatic, they have obvious association with congenital cardiovascular diseases and genetic diseases. These vascular variations lead to an increase in the difficulty and complication risk of surgery or endovascular procedures of the aorta and its branches as well as thoracic or head and neck surgeries. This paper reviewed that the types of variations of aorta branches, embryologic mechanism and the impact of these variations on clinical diagnosis and treatment.

The creative use of English idioms has led to heterogeneous idiom variants that are particularly problematic for L2 learners. Drawing on a cognitive linguistic perspective of idiom learning, this paper categorizes English idiom variants into four major types, and reports on an empirical study that investigated the effects of variation type and proficiency level on Chinese EFL learners' comprehension of English idiom variants. Targeting non-English major college students of basic and intermediate English levels, the study confirmed the influence of proficiency level on learners' comprehension and evaluation of the difficuIty of idiom variants. Structural change in idioms was found to be the easiest type and idioms modified in terms of literal imagery were the most difficult in comprehension. These findings suggest that the dominant 'rote memorization' tends to limit learners' choices of comprehension strategies to literal translation and L1 transfer. The learning environment unsupportive of cultivating L2 learners' analytical ability is held accountable for the generally low success rates in comprehension of idiom variants. [ABSTRACT FROM AUTHOR]