甲状腺激素抵抗综合征家系基因突变情况分析

目的观察一例甲状腺激素抵抗综合征(RTH)家系甲状腺激素β受体(TRβ)基因突变情况。方法收集该家系4名家庭成员及10名健康对照者外周血,提取基因组DNA,聚合酶链反应(PCR)扩增纯化后直接测序。结果未发现该家系TRβ基因突变。结论 TRβ基因突变并非导致RTH的惟一因素。     

成骨不全家系分析并文献复习

成骨不全症是以骨脆弱和骨畸形为临床特征的常染色体显性或隐性遗传缺陷的结缔组织病,临床罕见,根据主要临床表现和影像学结果来确诊。现发现成骨不全症家系一例,面对基因学和细胞学正在不断深入的研究,笔者以此家系为基础,对其发病机制、诊断、治疗及康复等问题予以阐述并文献复习。     

三种代谢综合征诊断标准在2型糖尿病家系人群中应用比较

目的 比较2005年美国国家胆固醇教育计划成人治疗方案第3次报告(ATPⅢ)、2005年国际糖尿病联盟(IDF)和2004年中华医学会糖尿病学分会(CDS)建议的代谢综合征(MS)诊断标准在2型糖尿病家系人群中应用的差异.方法 对715个2型糖尿病家系中有完整血压、血脂及血糖资料的4468名成员(包括配偶),由专门小组调查并采血样后,分别用ATPⅢ、IDF和CDS标准诊断MS,并比较MS患病率及诊断的一致性.结果 ATPⅢ、IDF和CDS标准诊断出的家系成员MS患病率分别为44.94%(2008/4468)、37.87%(1692/4468)、23.86%(1066/4468),均呈二级亲、配偶、一级亲、先证者逐渐升高的趋势[ATP Ⅲ标准诊断MS患病率分别为23.78%(117/492)、35.77%(318/889)、45.40%(1077/2372)、69.37%(496/715);IDF标准诊断MS患病率分别为20.53%(101/492)、31.61%(281/889)、38.74%(919/2372)、54.69%(391/715);CDS标准诊断MS患病率分别为8.94%(44/492)、16.99%(151/889)、25.08%(595/2372)、38.60%(276/715);ATPⅢ:X2趋势=266.359;IDF:X2趋势=155.950;CDS:X2趋势=165.087;P值均<0.01].用ATPⅢ、IDF诊断时,MS患病率女性明显高于男性[ATPⅢ:47.47%(1156/2435)、41.91%(852/2033);IDF:43.00%(1047/2435)、31.73%(645/2033);X2>值分别为13.871、60.169,P值均<0.01],而用CDS标准诊断时女性低于男性(分别为22.38%、25.63%,X2=6.423,P=0.011).ATPⅢ与IDF、ATPⅢ与CDS、IDF与CDS标准两两间的一致检出率分别为92.93%、75.56%和77.21%,其Kappa值分别为0.855、0.484和0.478(P值均<0.01).结论 在2型糖尿病家系人群中,ATPⅢ标准诊断的MS患病率及检出危险因素聚集的比例最高,更能反映该人群MS及其组分的特点.     

Computer-based genealogy reconstruction in founder populations

This paper describes a software tool that reconstructs entire genealogies from data collected from different and heterogeneous sources, including municipal and parish records archived over centuries. The tool exploits a record linkage algorithm relying on a rule-based data matching approach. It applies a general strategy for managing the ambiguities due to missing, imprecise or erroneous input data. The process follows an iterative approach that combines automatic pedigree reconstruction with software-empowered human data revision to improve the quality and the accuracy of the results and to optimize the matching rules.The paper discusses the results obtained by reconstructing the entire genealogy of the population of the Val Borbera, a geographically isolated valley in Northern Italy. The genealogy could be reconstructed from data going back as far as the XVI century. The resulting pedigree includes 75,994 trios, 58.9% of which belonging to a unique big family, reconstructed over 13 generations.     

遗传性非息肉病性大肠癌

目的：提高对遗传性非息肉病性大肠癌本质的认识。方法：对四个有遗传性非息肉病性大肠癌家系进行调查。结果：四家系共有14例病人,发病时平均年龄43岁。61．9％（13／21）的癌灶位于脾曲近端的大肠。大肠多原发癌占35．7％（5／14）。无结肠息肉病。四家系中之一为癌家族综合征。结论：对遗传性非息肉病性大肠癌前病人及其家系成员进行严密监测,争取疾病早诊断早治疗,提高治疗效果。     

三个遗传性血小板无力症家系临床表型和基因表型诊断的研究

目的对3个遗传性血小板无力症（glanzmann thrombasthenia，GT）家系进行血小板膜糖蛋白Ⅱb、Ⅲa（GPⅡb／GPⅢa）基因突变的检测。方法应用PCR对先证者GPⅡb／GPⅢa基因所有外显子及其侧翼序列进行扩增；PCR产物纯化后直接测序，检测其突变基因。突变位点经直接测序证实排除基因多态性。结果3个家系的先证者PLT均正常，血小板形态分散，出血时间（BT）延长，凝血象正常，对二磷酸腺苷（ADP）、凝血酶、肾上腺素、胶原、花生四烯酸等多种诱聚剂反应低下，而对瑞斯托霉素反应基本正常；家系1和家系2先证者的血小板膜表面CD41，（GPⅡb）／CD61（GPⅢa）的含量极度降低，分别为0．16％／1．8％、0．9％／3．7％，家系3先证者的血小板膜表面GPⅡb阳性血小板为10．1％，GPⅢa阳性血小板为12．8％。免疫印迹法几乎检测不到家系1和家系3先证者的α／Ⅱb。蛋白，家系2先证者的α／Ⅱb蛋白含量明显降低。家系1先证者在GPⅡb基因存在T2255G和C2671T复合杂合突变，家系2先证者在GPⅡb基因存在A2334C纯合突变，家系3先证者在GPⅡb基因存在C1750T和69-79del复合杂合突变。结论T2255G和C2671T复合杂合突变是导致家系1先证者发生GT的原因，A2334C纯合突变是导致家系2先证者发生GT的原因，C1750T和69-79del复合杂合突变是导致家系3先证者发生GT的原因。     

胆囊结石病家系载脂蛋白E基因型分析

目的：探索上海地区胆囊结石病家系的特点和Ａｐｏ Ｅ基因型与该病发病的关系。方法：对５８个胆囊结石病家系（胆囊结石病人１５９例,正常家系成员６１人）进行临床调查并检测血脂水平,采用ＰＣＲ·ＲＦＬＰ方法分析Ａｐｏ Ｅ基因型。结果：胆囊结石病有明显的家族聚集性,体重指数是家系成员发病的高危因素,Ａｐｏ Ｅ等位基因的频率分布为ε２（５．９％、ε３（８３．２％）和ε４（１０．９％,在胆石组中,Ｅ２／３基因型的血清ＡｐｏＢ浓度显著低于其他基因型,胆石组Ｅ２／３频率显著高于非胆石组（Ｐ＜０．０１）。结论：胆囊结石病家系中,不同Ａｐｏ Ｅ基因型的患者有不同的血脂变化特征,Ｅ２／３基因型可能是家系成员发病的一个危险因素。     

Pedigree likelihood formulae based on founder and founder couple symmetry and validation of DNA testing software

Pedigree likelihood ratios are widely used in forensic genetics. Linkage of genetic markers affects the pedigree likelihood ratio. In this study, a series of novel formulae was established based on simplification due to founder and founder couple symmetry of the Lander-Green algorithm for dealing with linkage. These new formulae are based on the inheritance vectors and differ from existing formulae that are based on the number of alleles shared identical-by-descent. In contrast to previous formulae, the formulae of this study expand the calculation to more general relationships, which enables specifying the number of typed individuals in pedigrees, and the new formulae are no longer limited to calculation of pairs of linked markers. Alternatively, pedigree likelihood values incorporating multiple linked markers could be obtained by iterating the vector transition probability between pairs of linkage markers and the probability of genotypes of typed individuals given inheritance vectors; the vector transition probability formulae are provided in a table form. To demonstrate utilization of the proposed formulae system, a series of cases were designed based on the relationships to validate GeneVisa software (www.genevisa.net) with frequency data of three linked markers, SE33-D6S1043-D6S474, on chromosome 6. The calculation results were verified with the FamLink software. The results demonstrated that the proposed formulae can correctly obtain the pedigree likelihood ratio, demonstrating the application potential of these formulae to verify effectiveness of DNA testing software.