Unraveling genetic predisposition to familial or early onset gastric cancer using germline whole-exome sequencing

Recognition of individuals with a genetic predisposition to gastric cancer (GC) enables preventive measures. However, the underlying cause of genetic susceptibility to gastric cancer remains largely unexplained. We performed germline whole-exome sequencing on leukocyte DNA of 54 patients from 53 families with genetically unexplained diffuse-type and intestinal-type GC to identify novel GC-predisposing candidate genes. As young age at diagnosis and familial clustering are hallmarks of genetic tumor susceptibility, we selected patients that were diagnosed below the age of 35, patients from families with two cases of GC at or below age 60 and patients from families with three GC cases at or below age 70. All included individuals were tested negative for germline CDH1 mutations before or during the study. Variants that were possibly deleterious according to in silico predictions were filtered using several independent approaches that were based on gene function and gene mutation burden in controls. Despite a rigorous search, no obvious candidate GC predisposition genes were identified. This negative result stresses the importance of future research studies in large, homogeneous cohorts

The effectiveness of a 3D virtual tooth identification test as an assessment tool for a dental anatomy course

IntroductionThere has been a recent demand in dental education for distance learning and the use of virtual assessment tools that can leverage technology to potentially replace physical testing facilities. However, virtual tools that evaluate student learning should be validated prior to adoption. The aim of this study was to investigate the effectiveness, efficiency and user satisfaction of a 3D tooth identification test for a dental anatomy course that can be given remotely.Materials and MethodsFirst-year dental students (n = 41) enrolled in a dental anatomy course took both traditional in-person practical and virtual 3D tooth identification tests consisting of 25 test items. The test scores, average test durations, faculty time commitment and user perception were collected and analysed. Pearson product-moment correlation coefficients (p < .05) were determined for the criterion measures including real tooth identification test scores, comprehensive written examination and overall grade for the course.ResultsThe average number of correct answers for the real and 3D virtual tooth identification examination was 21.3 ± 2.65 and 20.7 ± 2.56, respectively. The average test duration for the real and 3D virtual tooth identification test was 25:00 and 21:16 min, respectively. There was a positive correlation (p < .05) of the 3D virtual tooth identification test with the real tooth identification test (0.368), comprehensive written examination (0.334) and the overall course grade (0.646). The total faculty time commitment for the real and 3D virtual tooth identification test was 96 and 65 min, respectively. The students cited difficulty in manipulating the 3D models.ConclusionThis study presents evidence that the 3D virtual tooth identification test can be used to assess dental students’ understanding of dental anatomy effectively and efficiently.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/172289/1/eje12691_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/172289/2/eje12691.pd

Unraveling genetic predisposition to familial or early onset gastric cancer using germline whole-exome sequencing

Recognition of individuals with a genetic predisposition to gastric cancer (GC) enables preventive measures. However, the underlying cause of genetic susceptibility to gastric cancer remains largely unexplained. We performed germline whole-exome sequencing on leukocyte DNA of 54 patients from 53 families with genetically unexplained diffuse-type and intestinal-type GC to identify novel GC-predisposing candidate genes. As young age at diagnosis and familial clustering are hallmarks of genetic tumor susceptibility, we selected patients that were diagnosed below the age of 35, patients from families with two cases of GC at or below age 60 and patients from families with three GC cases at or below age 70. All included individuals were tested negative for germline CDH1 mutations before or during the study. Variants that were possibly deleterious according to in silico predictions were filtered using several independent approaches that were based on gene function and gene mutation burden in controls. Despite a rigorous search, no obvious candidate GC predisposition genes were identified. This negative result stresses the importance of future research studies in large, homogeneous cohorts

The common marmoset genome provides insight into primate biology and evolution

We report the whole-genome sequence of the common marmoset (Callithrix jacchus). The 2.26-Gb genome of a female marmoset was assembled using Sanger read data (6×) and a whole-genome shotgun strategy. A first analysis has permitted comparison with the genomes of apes and Old World monkeys and the identification of specific features that might contribute to the unique biology of this diminutive primate, including genetic changes that may influence body size, frequent twinning and chimerism. We observed positive selection in growth hormone/insulin-like growth factor genes (growth pathways), respiratory complex I genes (metabolic pathways), and genes encoding immunobiological factors and proteases (reproductive and immunity pathways). In addition, both protein-coding and microRNA genes related to reproduction exhibited evidence of rapid sequence evolution. This genome sequence for a New World monkey enables increased power for comparative analyses among available primate genomes and facilitates biomedical research application.The marmoset genome project was funded by the National Human Genome Research Institute (NHGRI), including from grants U54 HG003273 (R.A. Gibbs) and U54 HG003079 (R.K.W.), with additional support from the US National Institutes of Health (NIH), including from grants R01 DK077639 (S.D.T.), R01 GM59290 (L.B.J. and M.A.B.), HG002385 (E.E.E.) and P51-OD011133 (Southwest NPRC), and support from the National Science Foundation (NSF BCS-071508 to D.E.W.) and the VEGA grant agency: 1/0719/14 (T.V.) and 1/1085/12 (B.B.). C.C.F. and M.C.R. were supported in part by a Howard Hughes Medical Institute grant to Louisiana State University through the Undergraduate Biological Sciences Education program. J.X. was supported by NHGRI grant K99 HG005846. P.H.G. was supported by the Cullen Foundation. T.M.-B. was supported by European Research Council Starting Grant (260372) and MICINN (Spain) grant BFU2011-28549. B.L.-G. was supported by the Spanish National Institute of Bioinformatics (see URLs). E.E.E. is an investigator of the Howard Hughes Medical Institute