SMYD3 tandem repeats polymorphism is not associated with the occurrence and metastasis of hepatocellular carcinoma in a Chinese population

A variable number of tandem repeats (VNTR) polymorphism in regulatory region of SMYD3 coding for histone methyltransferase has been shown to be associated with colorectal cancer, hepatocellular carcinoma (HCC), and breast cancer in Japanese population. Aim of the study is to investigate the potential association between the functional SMYD3 tandem repeats polymorphism and HCC in Chinese population. Material and Methods: The case-control study included 200 HCC patients and 261 healthy controls. The VNTR polymorphism in the promoter of SMDY3 was genotyped by PCR and direct-sequencing analysis. Odds ratio and 95% confidence interval were used to estimate the association between the polymorphisms and risk of HCC. Results: The allele frequencies for SMYD3 2 and 3 repeats were 15.71% and 84.29% among controls; and 12.75%, and 87.25% among cases (P = 0.22). The odds ratio for 3/3 versus 2/2 and 2/3 genotypes was 1.30 (P = 0.18). The frequencies of 3 alleles were not increased with HCC stage increased (trend test, P = 0.45). Conclusion: SMYD3 polymorphism is not associated with the occurrence and metastasis of HCC in Chinese population.Известно, что полиморфизм тандемных повторов (VNTR) в регуляторном участке гена SMYD3,кодирующем метилтрансферазу гистонов, ассоциирован с развитием рака прямой кишки, карциномы печени (HCC) и рака молочной железы и является популяционно-зависимой характеристикой. Цель работы состояла в исследовании возможной связи междуVNTR Геном SMYD3 и развитием HCC у населения Китая. Материалы и методы: исследование типа “случай-контроль” проводили с участием 200 пациентов с HCC и 261 здорового донора. Полиморфизм VNTR в промоторной области гена SMDY3генотипировали методами PCR. Для оценки связи между полиморфизмом и риском развитияHCC использовали отношение шансов (OR) и 95% доверительные интервалы. Результаты: частота аллелей для повторов SMYD3 2 и 3 составила 15,71 и 84,29% в контрольной группе и 12,75 и 87,25% — в группе больных (P = 0,22). OR Генотипов 3/3 versus 2/2 и 2/3 составило 1,30 (P = 0.18). Частота 3 аллелей не возрастала при повышении стадии заболевания (P = 0,45). Выводы: полиморфизм гена SMYD3 не ассоциирован с развитием и метастазированием HCC у населения Китая

Exome chip association study excluded the involvement of rare coding variants with large effect sizes in the etiology of anorectal malformations

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Hirschsprung disease (HSCR) is a complex genetic disease characterized by absence of ganglia in the intestine. HSCR etiology can be explained by a unique combination of genetic alterations: rare coding variants, predisposing haplotypes and Copy Number Variation (CNV). Approximately 18% of patients have additional anatomical malformations or neurological symptoms (HSCR-AAM). Pinpointing the responsible culprits within a CNV is challenging as often many genes are affected. Therefore, we selected candidate genes based on gene enrichment strategies using mouse enteric nervous system transcriptomes and constraint metrics. Next, we used a zebrafish model to investigate whether loss of these genes affects enteric neuron development in vivo. This study included three groups of patients, two groups without coding variants in disease associated genes: HSCR-AAM and HSCR patients without associated anomalies (HSCR-isolated). The third group consisted of all HSCR patients in which a confirmed pathogenic rare coding variant was identified. We compared these patient groups to unaffected controls. Predisposing haplotypes were determined, confirming that every HSCR subgroup had increased contributions of predisposing haplotypes, but their contribution was highest in isolated HSCR patients without RET coding variants. CNV profiling proved that specifically HSCR-AAM patients had larger Copy Number (CN) losses. Gene enrichment strategies using mouse enteric nervous system transcriptomes and constraint metrics were used to determine plaus

Introducing the CTA concept

The Cherenkov Telescope Array (CTA) is a new observatory for very high-energy (VHE) gamma rays. CTA has ambitions science goals, for which it is necessary to achieve full-sky coverage, to improve the sensitivity by about an order of magnitude, to span about four decades of energy, from a few tens of GeV to above 100 TeV with enhanced angular and energy resolutions over existing VHE gamma-ray observatories. An international collaboration has formed with more than 1000 members from 27 countries in Europe, Asia, Africa and North and South America. In 2010 the CTA Consortium completed a Design Study and started a three-year Preparatory Phase which leads to production readiness of CTA in 2014. In this paper we introduce the science goals and the concept of CTA, and provide an overview of the project. © 2013 Elsevier B.V. All rights reserved