Chromatin interactions in differentiating keratinocytes reveal novel atopic dermatitis– and psoriasis-associated genes

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Characterization of genomic rearrangements of the alpha1-acid glycoprotein/orosomucoid gene in Ghanaians

In this study, the structure of the α₁-acid glycoprotein (AGP), or orosomucoid (ORM), gene was investigated in a Ghanaian mother and her child, who shared an unusual variant, ORM1 S2(C), found by isoelectric focusing. Three remarkable changes of nucleotide sequence were observed: (1) The two ORM1 alleles, ORM1 ^* S and ORM1 ^* S2(C), had the AGP2 gene-specific sequence at one and three regions, respectively, in exon 5 to intron 5. The variant allele originating from ORM1 ^* S was characterized by a G-to-A transition, resulting in an amino acid change from valine to methionine, which is also detected in ORM1 F2, a form that is common in Europeans. (2) The AGP2 gene of the child, inherited from the father, was duplicated, as revealed by long-range polymerase chain reaction. (3) Three new mutations were observed in two exons of the AGP2 genes of the mother and child. All of these novel genomic rearrangements, which were not observed in Japanese subjects, may have arisen through point mutation, gene conversion, and unequal crossover events. It is likely that the rearrangement of the AGP gene has often occurred in Africans. Received: June 15, 2001 / Accepted: July 10, 2001     

Genomic structure and eight novel exonic polymorphisms of the human N-cadherin gene

 Analysis of the detailed genomic structure of human N-cadherin revealed that the 16-exon gene is more than 72 kb in length and that it consists of a mosaic of exons. Five repeated cadherin domains, a transmembrane domain, and a cytoplasmic domain are encoded by exons 4 to 13, 13 and 14, and 14 to 16, respectively. A search for molecular variants in the entire coding region in 96 Japanese individuals resulted in the identification of eight sequence polymorphisms including three CCT- or GCC-type trinucleotide repeat polymorphisms adjacent to the initiation codon and five other novel single-nucleoticle polymorphisms (SNPs) in the coding region. Three of the five SNPs accompanied an amino acid substitution: Ala118Thr, Ala826Thr, and Asn845Ser. Knowlege of the fine gene structure and eight novel polymorphisms will be useful for the genetic study of the role of N-cadherin in diseases involving cell adhesion in the brain and in cardiomyocytes. Received: January 23, 2002 / Accepted: March 12, 2002     

Ethnic variation in the HER-2 codon 655 genetic polymorphism previously associated with breast cancer

HER-2, a protooncogene located on chromosome 17q21, encodes a transmembrane glycoprotein (p185) with tyrosine kinase activity. Alterations of the HER-2 gene have been implicated in the carcinogenesis and prognosis of breast cancer and other solid tumors. It is also a cancer-therapeutic target for antibody-based therapy against the HER-2 protein. A single-nucleotide polymorphism (SNP) at codon 655, resulting in a G-to-A transition (Ile655Val) in the transmembrane domain-coding region of this gene has been associated with an increased risk of breast cancer, particularly among younger women. To understand the importance of this finding throughout the world, we evaluated this polymorphism in Ghanaian, Kenyan, Sudanese, Caucasian, African–American, Saudi, and Filipino subjects using a polymerase chain reaction-restriction fragment length polymorphism assay. The frequency of the Val allele, which is associated with increased breast cancer risk, was highly variable between populations (0%–24%). Continental African populations had a lower frequency of the Val allele than did Saudi, Chinese, Filipino, Caucasian, and African–American subjects. The data suggest that this SNP has variable frequency in different ethnic groups. The findings in this study correspond with the lower incidence and lower risk of breast cancer in African women compared with Caucasian and African–American women. Received: December 13, 2001 / Accepted: January 16, 2002     

Genetic variations in five genes involved in the excitement of cardiomyocytes

We provide here 29 genetic variations, including 28 novel ones, in five genes that are potentially involved in the excitement of cardiomyocytes: we found 4 in KCNA10, 2 in KCNK1, 8 in KCNK6, 11 in SLC18A1 (VMAT1), and 4 in SLC6A2 (norepinephrine transporter). We also examined their allelic frequencies in a Japanese population of long QT syndrome-affected and nonaffected individuals. These data would be useful for genetic association studies designed to investigate acquired arrhythmias. Received: May 22, 2001 / Accepted: June 8, 2001     

组织激肽释放酶基因调控序列多态性与高血压关系的初步分析

目的　初步探讨组织激肽释放酶基因调控序列启动子多态性与中国人原发性高血压 (EH)的相关性。方法　应用PCR技术结合等位基因特异寡核苷酸片段分析 (ASO)方法 ,对 40例EH患者和正常人的组织激肽释放酶基因用A、B两种探针检测 ,比较两组间的等位基因分布频率差异 ,初步分析该SNP位点与高血压的关系。结果　组织激肽释放酶基因A、B型在对照组中频率为 65 %、10 % ,在高血压组中频率为 60 %、10 % ,两组比较有差异 ,但无统计学意义。结论　在中国汉族人群中 ,该基因位点确实有多态性 ;A、B两型均有分布 ,以A型最广     

白细胞介素-18基因rs1946518位点多态性与肠道病毒71型感染易感性的关系

目的 探讨白细胞介素(interleukin,IL)-18基因rs1946518位点多态性与肠道病毒71型(enterovirus 71,EV71)感染易感性及其与EV71感染致病严重程度之间的相关性.方法 选取2012年3月至2014年12月湖南省湘潭市中心医院确诊的EV71感染患儿123例作为研究对象(EV71感染组),匹配同期在我院健康体检的52例儿童作为对照组.其中EV71感染组分为轻症EV71感染组(简称轻症组,n=62)和重症EV71感染组(简称重症组,n=61),提取DNA后通过测序分析IL-18基因rs1946518位点多态性.结果 EV71感染组与对照组均存在rs1946518位点多态性,EV71感染组AA、AC、CC基因频率分别为27.64%、50.41%、21.95%,A等位基因及C等位基因的频率分别为52.85%、47.15%,对照组AA、AC、CC的基因频率分别为26.92%、42.31%、30.77%,A等位基因及C等位基因的频率分别为48.07%、51.93%,EV71感染组与对照组基因型及等位基因频率经统计学分析,差异无统计学意义(P<0.05).轻症组AA、AC、CC的基因频率分别为14.51%、54.84%、30.65%,A等位基因及C等位基因的频率分别为41.94%、58.06%;重症组AA、AC、CC的基因频率分别为40.98%、45.90%、13.12%.A等位基因及C等位基因的频率分别为63.93%、36.07%,轻症组与重症组基因型分布频率差异具有统计学意义(χ2=12.58,P=0.002).轻症组与重症组等位基因频率差异亦具有统计学意义(χ2=11.94,P=0.001,OR=2.455,95%CI 1.496-4.102).结论 IL-18 rs1946518A/C位点基因多态性与EV71感染严重程度之间有一定程度的相关性,携带IL-18 rs1946518A等位基因的感染患儿进展为重症的概率较高.     

A preliminary identification of PIN1 SNP linkage in patients with coronary heart disease from Handan,China

Our aim was to perform an initial assessment of the polymorphic patterns of the PIN1 gene in patients with coronary heart disease (CHD). The PIN1-encoded protein (Pin1) suppresses eNOS-NO signaling and may impair cardiovascular function. Blood collection, DNA extraction, PCR amplification and gene sequencing were performed for thirty CHD participants living in central China, focusing on nine single nucleotide polymorphisms (SNPs). Their genetic linkages were revealed and their allele frequencies were compared with SNP data from the NCBI. Three major linkage patterns were identified: [1.rs2287839-5.rs2233682], [3.rs2233679-4.rs1077220–8.rs2287838] and [6.rs889162-7.rs2010457], suggesting correlated involvement in CHD and possible simultaneous genetic origin in ancient times. The frequencies of six SNPs are consistent with the NCBI data, while the frequencies of three SNPs (2.rs2233678, 4.rs1077220 and 9.rs4804461) are not consistent with the NCBI. Especially, the 3.rs2233679–4.rs1077220 linkage is different from other populations worldwide and may be an interesting genetic characteristic of Chinese CHD patients. Predictably, 1.rs2287839, 2.rs2233678, 3.rs2233679 and 5.rs2233682 may be strongly associated with CHD risk, although this requires future verification. The PIN1 SNP linkages lay a new genetic foundation for discovering novel molecular mechanisms of CHD and for exploring PIN1-based targeted treatment of CHD with nitric oxide regulatory therapies in clinical practice.