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Geneticists have, for years, understood the nature of genome‐wide association studies using common genomic variants. Recently, however, focus has shifted to the analysis of rare variants. This presents potential problems for researchers, as rare variants do not always behave in the same way common variants do, sometimes rendering decades of solid intuition moot. In this paper, we present examples of the differences between common and rare variants. We show why one must be significantly more careful about the origin of rare variants, and how failing to do so can lead to highly inflated type I error. We then explain how to best avoid such concerns with careful understanding and study design. Additionally, we demonstrate that a seemingly low error rate in next‐generation sequencing can dramatically impact the false‐positive rate for rare variants. This is due to the fact that rare variants are, by definition, seen infrequently, making it hard to distinguish between errors and real variants. Compounding this problem is the fact that the proportion of errors is likely to get worse, not better, with increasing sample size. One cannot simply scale their way up in order to solve this problem. Understanding these potential pitfalls is a key step in successfully identifying true associations between rare variants and diseases. 相似文献
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目的 基于基因组Survey分析对刺果甘草Glycyrrhiza pallidiflora Maxim.基因组大小和杂合率进行估计,并通过叶绿体基因组序列特征对其在甘草属Glycyrrhiza L.中的系统发育位置进行研究。方法 使用二代测序技术对刺果甘草进行测序,采用K-mer方法对测序reads进行分析,估算刺果甘草基因组大小和杂合率,使用生物信息学方法进行叶绿体基因组组装、注释和系统发育分析。结果 Survey分析结果显示其基因组大小约为577.82 Mb,杂合度约为0.31%,重复序列比例约为53.72%。叶绿体基因组长度为127,267 bp,不具有典型的四分体结构,总GC含量为34.32%,包含110个基因,其中76个蛋白质编码基因,30个tRNA基因和4个rRNA基因。系统发育分析表明,刺果甘草与圆果甘草G. squamulosa Franch.亲缘较接近。结论 刺果甘草存在低杂合和重复序列较多的特点,为了更好地对全基因组进行序列拼接和组装,可尝试采用三代测序结合二代测序的分析策略进行基因组组装;刺果甘草叶绿体全基因组比对和系统发育分析,为后续开展甘草属遗传多样性研究和分子鉴定标记筛选提供了重要依据。 相似文献
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《Clinical oncology (Royal College of Radiologists (Great Britain))》2022,34(10):653-669
AimsPatient factors affect the risk of radiotherapy toxicity, but many are poorly defined. Studies have shown that race affects cancer incidence, survival, drug response, molecular pathways and epigenetics. Effects on radiosensitivity and radiotherapy toxicity are not well studied. The aim of the present study was to identify the effects of race and ethnicity on the risk of radiotherapy toxicity.Materials and methodsA systematic review was carried out of PubMed, Ovid Medline and Ovid Embase with no year limit. PRISMA 2020 guidelines were followed. Two independent assessors reviewed papers.ResultsOf 607 papers screened, 46 fulfilled the inclusion criteria. Papers were published between 1996 and 2021 and involved 30–28,354 individuals (median 433). Most involved patients with prostate (33%), breast (26%) and lung (9%) cancer. Both early and late toxicities were studied. Some studies reported a higher risk of toxicity in White men with prostate cancer compared with other races and ethnicities. For breast cancer patients, some reported an increased risk of toxicity in White women compared with other race and ethnic groups. In general, it was difficult to draw conclusions due to insufficient reporting and analysis of race and ethnicity in published literature.ConclusionsReporting of race and ethnicity in radiotherapy studies must be harmonised and improved and frameworks are needed to improve the quality of reporting. Further research is needed to understand how ancestral heritage might affect radiosensitivity and risk of radiotherapy toxicity. 相似文献
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Micro‐evolution of the hepatitis B virus genome in hepatitis B e‐antigen‐positive carriers: Comparison of genotypes B and C at various immune stages
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《Molecular therapy》2020,28(6):1432-1441
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Vincent Laville Sigrid Le Clerc Khaled Ezzedine Randa Jdid Lieng Taing Toufik Labib Cdric Coulonges Damien Ulveling Pilar Galan Christiane Guinot Leopold Fezeu Frdrique Morizot Julie Latreille Denis Malvy Erwin Tschachler Jean‐Franois Zagury 《Experimental dermatology》2019,28(8):892-898
Sagging eyelid is considered as an outward of skin ageing and may cause medical issues. However, little is known about the factors involved in sagging eyelid. The study, which aims at determining genetic risk factors for eyelid sagging, was conducted in a cohort of 502 unrelated Caucasian women living in the Paris region. All included participants were aged between 44 and 70 years old (mean age, 57.6 years old). The severity of sagging eyelid was graded in 6 categories by a dermatologist using standardized photographs of the face. A genome wide association study adjusted on potential risk factors (including age and smoking habits) was conducted to identify genetic associations. Two single nucleotide polymorphisms in total linkage disequilibrium on chromosome 10, rs16927253 (P = 7.07 × 10‐10) and rs4746957 (P = 1.06 × 10‐8), were significantly associated with eyelid sagging severity. The rs16927253‐T and rs4746957‐A alleles showed a dominant protective effect towards eyelid sagging. These polymorphisms are located in intronic parts of the H2AFY2 gene which encodes a member of the H2A histone family and very close to the AIFM2 gene that induces apoptosis. Additionally, single nucleotide polymorphisms with a false discovery rate below 0.25 were located nearby the type XIII collagen COL13A1 gene on chromosome 10 and in the ADAMTS18 gene on chromosome 16. Several relevant genes were identified by the genome wide association study for their potential role in the sagging eyelid severity. 相似文献
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In a genetic epidemiology study of a trait, prior to collecting genotype data the foremost task is to test for familial aggregation and examine heritability. Recently, functional traits have drawn attentions from investigators. Here, to test for familial aggregation of a functional trait in the family studies, a test constructed based on the leading functional principal component of heritability, which is a summary measure of temporal genetic variation in a functional trait, is proposed. The p‐value of the test can be approximated by a permutation procedure given the family structure. The asymptotic distribution of the test statistic is derived. Simulations are carried out to examine the size and the power of the test. The proposed methods are applied to the total cholesterol data in the Framingham Heart Study. Copyright © 2009 John Wiley & Sons, Ltd. 相似文献