Most biological traits of human importance are complex in nature; their manifestation controlled by the cumulative effect of many genetic factors interacting with one another and with the individual's life history. Because of this, mouse genetic reference populations (GRPs) consisting of collections of inbred lines or recombinant inbred lines (RIL) derived from crosses between inbred lines are of particular value in analysis of complex traits, since massive amounts of data can be accumulated on the individual lines. However, existing mouse GRPs are derived from inbred lines that share a common history, resulting in limited genetic diversity, and reduced mapping precision due to long-range gametic disequilibrium. To overcome these limitations, the Collaborative Cross (CC) a genetically highly diverse collection of mouse RIL was established. The CC, now in advanced stages of development, will eventually consist of about 500 RIL derived from reciprocal crosses of eight divergent founder strains of mice, including three wild subspecies. Previous studies have shown that the CC indeed contains enormous diversity at the DNA level, that founder haplotypes are inherited in expected frequency, and that long-range gametic disequilibrium is not present. We here present data, primarily from our own laboratory, documenting extensive genetic variation among CC lines as expressed in broad-sense heritability (H(2)) and by the well-known "coefficient of genetic variation," demonstrating the ability of the CC resource to provide unprecedented mapping precision leading to identification of strong candidate genes.
BackgroundColorectal cancer is an abnormal tissue development in the colon or rectum. Most of CRCs develop due to somatic mutations, while only a small proportion is caused by inherited mutations. Familial adenomatous polyposis is an inherited genetic disease, which is characterized by colorectal polyps. It is caused by inactivating mutations in the Adenomatous polyposis coli gene. Mice carrying and non-sense mutation in Adenomatous polyposis coli gene at site R850, which designated ApcR850X/+ (Min), develop intestinal adenomas, while the bulk of the disease is in the small intestine. A number of genetic modifier loci of Min have been mapped, but so far most of the underlying genes have not been identified. In our previous studies, we have shown that Collaborative Cross mice are a powerful tool for mapping loci responsible for phenotypic variation. As a first step towards identification of novel modifiers of Min, we assessed the phenotypic variation between 27 F1 crosses between different Collaborative cross mice and C57BL/6-Min lines.ResultsHere, C57BL/6-Min male mice were mated with females from 27 Collaborative cross lines. F1 offspring were terminated at 23 weeks old and multiple phenotypes were collected: polyp counts, intestine length, intestine weight, packed cell volume and spleen weight. Additionally, in eight selected F1 Collaborative cross-C57BL/6-Min lines, body weight was monitored and compared to control mice carry wildtype Adenomatous polyposis coli gene. We found significant (p < 0.05) phenotypic variation between the 27 F1 Collaborative cross-C57BL/6-Min lines for all the tested phenotypes, and sex differences with traits; Colon, body weight and intestine length phenotypes, only. Heritability calculation showed that these phenotypes are mainly controlled by genetic factors.ConclusionsVariation in polyp development is controlled, an appreciable extent, by genetic factors segregating in the Collaborative cross population and suggests that it is suited for identifying modifier genes associated with ApcMin/+ mutation, after assessing sufficient number of lines for quantitative trait loci analysis.Electronic supplementary materialThe online version of this article (doi:10.1186/s12863-016-0349-6) contains supplementary material, which is available to authorized users.
Background: Use of standardized (or simulated) patients (SP) is considered an effective teaching method for improving clinical and communication skills. This study assesses the effect of a single-day simulated patients (SP)-based training course on medical students' communication and basic skills in clinical psychiatry during their psychiatry rotation in a university-affiliated tertiary medical center. Methods: Forty-two third-year medical students participated. Communication and basic skills in clinical psychiatry were evaluated by a modified Four Habits Coding Scale (4HCS) and the psychiatric interview coding scale before and after SP training. An actual patient interview by the students 1 week after the training was evaluated by an attending psychiatrist blinded to the student's score during the SP-based training. Self-report questionnaires on satisfaction from the training and its impact on their self-confidence were administered at the end of training. Findings: The mean pre-training 4HCS score of 33.9 increased to 52.3 post-training (p < 0.001). The mean psychiatric interview coding scale score increased from 4.33 to 5.36 (p = 0.002). The self-report questionnaire yielded a mean score of 4.21 on a 1-5 Likert scale, implying high levels of satisfaction and self-confidence. Conclusions: A single SP-based training course of medical students sufficed to improve clinical and communication skills in psychiatric settings and enhance their subjective perception of those skills.
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