目的探讨喉鳞状细胞癌变过程中微卫星DNA等位基因不平衡性的特征及其意义。方法选取染色体3P、9P和17P上6个多态性微卫星位点D3S1234、D9S171、D9S1748、D9S162、INFA和D17S796,利用聚合酶链式反应-简单序列长度多态性-银染技术,对49例...目的探讨喉鳞状细胞癌变过程中微卫星DNA等位基因不平衡性的特征及其意义。方法选取染色体3P、9P和17P上6个多态性微卫星位点D3S1234、D9S171、D9S1748、D9S162、INFA和D17S796,利用聚合酶链式反应-简单序列长度多态性-银染技术,对49例喉癌癌前病变和喉癌组织进行等位基因不平衡分析,统计杂合性缺失(loss of heterozygosi-ty,LOH)和微卫星不稳定性(microsatellite instability,MSI)的发生率及其与临床病理特征的相关性。结果6个微卫星标记物LOH和MSI发生率分别为:喉癌癌前病变中单纯过度增生为3.7%和14.8%,轻度不典型增生为10.8%和21.6%,重度不典型增生为26.0%和23.3%;喉鳞状细胞癌为38.7%和21.3%。其中LOH的总检出率在不同病理组间有统计学意义(χ2=17.686,P=0.000),而MSI的检出率统计学意义(χ2=0.314,P>0.05)。不同病理组间D9S171和D9S162单个位点LOH检出率有统计学意义(P=0.022,P=0.025)。在癌前病变早期MSI发生率高于LOH。结论等位基因不平衡可能参与喉癌发生发展,微卫星分析法为喉癌癌前病变的早期诊断提供新的途径。展开更多
Currently, there is great interest in identifying genetic variants that contribute to the risk of developing autism spectrum disor- ders （ASDs）, due in part to recent increases in the frequency of diagnosis of these...Currently, there is great interest in identifying genetic variants that contribute to the risk of developing autism spectrum disor- ders （ASDs）, due in part to recent increases in the frequency of diagnosis of these disorders worldwide. While there is nearly universal agreement that ASDs are complex diseases, with multiple genetic and environmental contributing factors, there is less agreement concerning the relative importance of common vs rare genetic variants in ASD liability. Recent observations that rare mutations and copy number variants （CNVs） are frequently associated with ASDs, combined with reduced fecundity of individuals with these disorders, has led to the hypothesis that ASDs are caused primarily by de novo or rare genetic muta- tions. Based on this model, large-scale whole-genome DNA sequencing has been proposed as the most appropriate method for discovering ASD liability genes. While this approach will undoubtedly identity many novel candidate genes and produce important new insights concerning the genetic causes of these disorders, a full accounting of the genetics of ASDs will be incomplete absent an understanding of the contributions of common regulatory variants, which are likely to influence ASD liability by modifying the effects of rare variants or, by assuming unfavorable combinations, directly produce these disorders. Because it is not yet possible to identify regulatory genetic variants by examination of DNA sequences alone, their identitication will require experimentation. In this essay, I discuss these issues and describe the advantages of measurements of allelic expression imbalance （AEI） of mRNA expression for identifying cis-acting regulatory variants that contribute to ASDs.展开更多
文摘目的探讨喉鳞状细胞癌变过程中微卫星DNA等位基因不平衡性的特征及其意义。方法选取染色体3P、9P和17P上6个多态性微卫星位点D3S1234、D9S171、D9S1748、D9S162、INFA和D17S796,利用聚合酶链式反应-简单序列长度多态性-银染技术,对49例喉癌癌前病变和喉癌组织进行等位基因不平衡分析,统计杂合性缺失(loss of heterozygosi-ty,LOH)和微卫星不稳定性(microsatellite instability,MSI)的发生率及其与临床病理特征的相关性。结果6个微卫星标记物LOH和MSI发生率分别为:喉癌癌前病变中单纯过度增生为3.7%和14.8%,轻度不典型增生为10.8%和21.6%,重度不典型增生为26.0%和23.3%;喉鳞状细胞癌为38.7%和21.3%。其中LOH的总检出率在不同病理组间有统计学意义(χ2=17.686,P=0.000),而MSI的检出率统计学意义(χ2=0.314,P>0.05)。不同病理组间D9S171和D9S162单个位点LOH检出率有统计学意义(P=0.022,P=0.025)。在癌前病变早期MSI发生率高于LOH。结论等位基因不平衡可能参与喉癌发生发展,微卫星分析法为喉癌癌前病变的早期诊断提供新的途径。
基金supported by the National Basic Research Program of China(Grant No.2010CB529600)the National Natural Science Foundation of China(Grant No.30870899)
文摘Currently, there is great interest in identifying genetic variants that contribute to the risk of developing autism spectrum disor- ders （ASDs）, due in part to recent increases in the frequency of diagnosis of these disorders worldwide. While there is nearly universal agreement that ASDs are complex diseases, with multiple genetic and environmental contributing factors, there is less agreement concerning the relative importance of common vs rare genetic variants in ASD liability. Recent observations that rare mutations and copy number variants （CNVs） are frequently associated with ASDs, combined with reduced fecundity of individuals with these disorders, has led to the hypothesis that ASDs are caused primarily by de novo or rare genetic muta- tions. Based on this model, large-scale whole-genome DNA sequencing has been proposed as the most appropriate method for discovering ASD liability genes. While this approach will undoubtedly identity many novel candidate genes and produce important new insights concerning the genetic causes of these disorders, a full accounting of the genetics of ASDs will be incomplete absent an understanding of the contributions of common regulatory variants, which are likely to influence ASD liability by modifying the effects of rare variants or, by assuming unfavorable combinations, directly produce these disorders. Because it is not yet possible to identify regulatory genetic variants by examination of DNA sequences alone, their identitication will require experimentation. In this essay, I discuss these issues and describe the advantages of measurements of allelic expression imbalance （AEI） of mRNA expression for identifying cis-acting regulatory variants that contribute to ASDs.
