白化病的遗传流行病学研究

本文应用分离分析和血缘分析方法,对山东省１００余万人群遗传病调查中发现的３７个白化病核心家系进行了分析。结果表明：白化病存在遗传异质性,为多基因常染色体隐性遗传,最小基因数为８,平均基因频率为０．００２３,群体中致病基因携带者频率为０．０３８３;近亲结婚大大提高白化病的患病率。     

遗传病遗传类型的确定

遗传病遗传类型的确定李德启（黑龙江省大庆市大庆中学１６３７１２）在高中生物课的习题中,根据遗传病的家谱图可提出写个体的基因型、遗传几率的计算等一系列问题。而确定该遗传病属于何种遗传类型是回答这些问题的前提。１单基因遗传病的遗传特点人类遗传病的类型就基...     

印记遗传

印迹遗传是一种的遗传方式,其主要特征是：在配子形成时期,亲本对基因组的某些部分作专一性修饰或其它标记。等位基因因是否被标记而在子代中有不同的表型。遗传鲩迹可能与ＤＮＡ的甲基化有关,现在已发现很多人类遗传与遗传印迹有关。因此对遗传印的进一步有助于揭示人类遗传病的发生机制和对遗传病的治疗。     

后腹腔镜肾囊肿去顶减压术治疗成人型多囊肾的疗效观察

目的评价后腹腔镜肾囊肿去顶减压术治疗多囊肾的临床疗效。方法2005年1月至2009年12月期间,行后腹腔镜肾囊肿去顶减压术的ADPKD患者17例,于术后1月、6月进行随访,观察患者的腰腹部胀痛情况、血压、血清肌酐、GFR的变化。结果腰腹部胀痛、血压明显低于术前,但随着时间推移,效果有所减弱;血清肌酐、GFR无变化。结论对于单侧症状明显的多囊肾患者,行后腹腔镜肾囊肿去顶减压术能改善腰腹部胀痛及血压。     

3D-PDUS对成人常染色体显性遗传多囊肾病肾脏血流动力学变化的研究

目的:应用三维能量多普勒超声技术探讨成人常染色体显性多囊肾病(ADPKD)患者肾脏血流灌注的改变与血压的关系。方法:选取79例ADPKD患者;对照组86例,其中包括62例原发性高血压(EH)患者以及24例血压正常的健康成年人。使用三维能量多普勒超声采集肾脏三维能量图像并应用VOCAL分析软件得出相关参数指标:血管指数(VI)、血流指数(FI)、血管血流指数(VFI)及肾脏总体积。结果:(1)与同级别血压水平的对照组比较,在ADPKD患者血压正常时VI就开始减低、肾脏总体积就开始增大(P0.05);(2)ADPKD合并高血压1级、2级、3级患者与同级别血压水平的对照组相比,其VI明显下降、肾脏总体积显著增大(P0.01),预示着ADPKD疾病的进展,ADPKD血流动力学变化与血压的变化关系密切。结论:ADPD患者血流动力学的变化比血压的变化更敏感。故早期对多囊肾患者肾脏血流动力学进行监测,对于评估病情、判定疗效、指导临床治疗具有重要意义。     

人类与性别有关的遗传病的遗传方式

一般情况下 ,常染色体上基因控制的性状或人类遗传病 ,在男女两种性别中的表现程度或发病率基本一致 ,所以一般不出现性别上的比例差异。而性染色体上的基因控制的性状或遗传病 ,由于性染色体在两性间的分配不一致 ,而在两性间出现比例上的差异。这就是为人熟知的伴性遗传。但是有时常染色体上基因控制的性状或遗传病 ,在两性间的表现程度或发病率也不一致 ,其表现也与性别有关 ,如从性遗传和限性遗传。下面本文就各遗传方式的特点及异同分别做一叙述。1　伴性遗传、从性遗传和限性遗传的特点1.1　伴性遗传　人类属 XY型性决定生物 ,由于性…     

隐性遗传与禁止近亲结婚

人类遗传病分单基因、染色体和多基因遗传病三大类。单基因遗传病又分常染色体显性、隐性和伴性遗传三种方式,其中伴性遗传也有显、隐性之分。伴性遗传依基因位于哪条性染色体上,分X和Y连锁遗传。由于Y染色体过短小,上面只有少数基因,这类遗传病故很少见。     

涉及两种遗传病的遗传题的解法研究

关于人类遗传病的发病机率 (或正常子女出现机率 )的计算 ,特别是涉及两种遗传病的发病率的计算 ,是高考试卷中常会出现的类型 ,而这类题又是绝大多数考生十分“头疼”的问题。为了帮助学生解题 ,笔者结合自己多年的教学以一道题为例谈一下该类型题的解法 ,供同行们参考。例题　人类多指基因 (T)对正常指基因 (t)是显性 ,白化基因 (a)对正常基因 (A)为隐性 ,且都在常染色体上 ,而且都是独立遗传。一个家庭中 ,父亲是多指 ,母亲正常 ,他们有一个白化病和手指正常的孩子 ,则下一个孩子两种病均患的概率、只患一种病的概率、患病概率及完全正…     

与优生遗传有关的2个问题

1　为什么越是罕见的常染色体隐性遗传病 ,近亲婚配时子代的发病风险比随机婚配越高我们知道 ,一级亲属 (父母与子女、兄妹等 )之间基因相同的可能性为 1/ 2 ,二级亲属 (祖孙、外祖孙、叔侄、舅甥等 )之间基因相同的可能性为 1/ 4 ,而三级亲属 (表兄妹、堂兄妹 )之间的可能性为 1/ 8。设在群体中某种常染色体隐性遗传病的发病率为10 -4。根据 Hardy- Weiberg定律的公式 :p2 + 2 pq+ q2 =1和 p+ q=1,则发病率 =p(aa) =q2 =10 -4,隐性致病基因的频率 p=q2 =0 .0 1,显性基因的频率 p=1- q=1-0 .0 1=0 .99;群体中携带者的频率 p(Aa) =2 pq=2×…     

多囊肝病的治疗及进展

多囊肝病(polycystic liver diseases,PLD)是一种罕见的遗传性疾病,囊肿可单独出现于肝脏(常染色体显性遗传性多囊肝病)或者合并肾脏囊肿(常染色体显性遗传性多囊肾病)。PLD是良性疾病,囊肿的体积和数量会持续不断的增长但肝脏功能不受影响。大部分患者无临床症状,无需治疗或仅需保守治疗。少数患者会因肝肿大占位效应或囊肿并发症而产生严重的临床症状时需要治疗,目的主要是减小肝脏的体积,治疗方法包括抽吸硬化术、开窗术、部分肝切除术、肝动脉栓塞术、肝脏移植术及药物治疗等。本文对PLD的治疗及进展进行综述。     

A Possible Zebrafish Model of Polycystic Kidney Disease: Knockdown of wnt5a Causes Cysts in Zebrafish Kidneys

Polycystic kidney disease (PKD) is one of the most common causes of end-stage kidney disease, a devastating disease for which there is no cure. The molecular mechanisms leading to cyst formation in PKD remain somewhat unclear, but many genes are thought to be involved. Wnt5a is a non-canonical glycoprotein that regulates a wide range of developmental processes. Wnt5a works through the planar cell polarity (PCP) pathway that regulates oriented cell division during renal tubular cell elongation. Defects of the PCP pathway have been found to cause kidney cyst formation. Our paper describes a method for developing a zebrafish cystic kidney disease model by knockdown of the wnt5a gene with wnt5a antisense morpholino (MO) oligonucleotides. Tg(wt1b:GFP) transgenic zebrafish were used to visualize kidney structure and kidney cysts following wnt5a knockdown. Two distinct antisense MOs (AUG - and splice-site) were used and both resulted in curly tail down phenotype and cyst formation after wnt5a knockdown. Injection of mouse Wnt5a mRNA, resistant to the MOs due to a difference in primary base pair structure, rescued the abnormal phenotype, demonstrating that the phenotype was not due to “off-target” effects of the morpholino. This work supports the validity of using a zebrafish model to study wnt5a function in the kidney.     

Exploitation of the Polymeric Immunoglobulin Receptor for Antibody Targeting to Renal Cyst Lumens in Polycystic Kidney Disease

Autosomal-dominant polycystic kidney disease (ADPKD) is a common life-threatening genetic disease that leads to renal failure. No treatment is available yet to effectively slow disease progression. Renal cyst growth is, at least in part, driven by the presence of growth factors in the lumens of renal cysts, which are enclosed spaces lacking connections to the tubular system. We have shown previously shown that IL13 in cyst fluid leads to aberrant activation of STAT6 via the IL4/13 receptor. Although antagonistic antibodies against many of the growth factors implicated in ADPKD are already available, they are IgG isotype antibodies that are not expected to gain access to renal cyst lumens. Here we demonstrate that targeting antibodies to renal cyst lumens is possible with the use of dimeric IgA (dIgA) antibodies. Using human ADPKD tissues and polycystic kidney disease mouse models, we show that the polymeric immunoglobulin receptor (pIgR) is highly expressed by renal cyst-lining cells. pIgR expression is, in part, driven by aberrant STAT6 pathway activation. pIgR actively transports dIgA from the circulation across the cyst epithelium and releases it into the cyst lumen as secretory IgA. dIgA administered by intraperitoneal injection is preferentially targeted to polycystic kidneys whereas injected IgG is not. Our results suggest that pIgR-mediated transcytosis of antagonistic antibodies in dIgA format can be exploited for targeted therapy in ADPKD.     

Fibrosis and progression of Autosomal Dominant Polycystic Kidney Disease (ADPKD)

The age on onset of decline in renal function and end-stage renal disease (ESRD) in autosomal polycystic kidney disease (ADPKD) is highly variable and there are currently no prognostic tools to identify patients who will progress rapidly to ESRD. In ADPKD, expansion of cysts and loss of renal function are associated with progressive fibrosis. Similar to the correlation between tubulointerstitial fibrosis and progression of chronic kidney disease (CKD), in ADPKD, fibrosis has been identified as the most significant manifestation associated with an increased rate of progression to ESRD. Fibrosis in CKD has been studied extensively. In contrast, little is known about the mechanisms underlying progressive scarring in ADPKD although some commonality may be anticipated. Current data suggest that fibrosis associated with ADPKD shares at least some of the “classical” features of fibrosis in CKD (increased interstitial collagens, changes in matrix metalloproteinases (MMPs), over-expression of tissue inhibitor of metalloproteinase-1 (TIMP-1), over-expression of plasminogen activator inhibitor-1 (PAI-1) and increased transforming growth factor beta (TGFβ) but that there are also some unique and stage-specific features. Epithelial changes appear to precede and to drive interstitial changes leading to the proposal that development of fibrosis in ADPKD is biphasic with alterations in cystic epithelia precipitating changes in interstitial fibroblasts and that reciprocal interactions between these cell types drives progressive accumulation of extracellular matrix (ECM). Since fibrosis is a major component of ADPKD it follows that preventing or slowing fibrosis should retard disease progression with obvious therapeutic benefits. The development of effective anti-fibrotic strategies in ADPKD is dependent on understanding the precise mechanisms underlying initiation and progression of fibrosis in ADPKD and the role of the intrinsic genetic defect in these processes. This article is part of a Special Issue entitled: Polycystic Kidney Disease.     

Polycystic nephropathy in slender lorises (Loris lydekkerianus)

In a colony of slender lorises, 20 deaths that occurred over a period of 11 years were investigated postmortem. Juvenile/adult polycystic nephropathy was observed in one newborn and 13 adult slender lorises. Although polycystic kidney disease (PKD) in humans and other animals is known to be inherited, it is not clear whether kidney alterations in slender lorises are genetically transmitted, stress related, or induced by microbiological influences.     

Adult Polycystic Kidney Disease in a Rhesus Monkey (Macaca mulatta)

Adult polycystic kidney disease was diagnosed at necropsy in a 16-year-old rhesus monkey dead from renal failure. Both kidneys were enlarged and contained multiple cysts ranging from 0.1 to 4.0 cm in diameter. The age of onset of the clinical signs, terminal uremia, and the gross and histologic findings in this macaque were consistent with adult (type III) polycystic kidney disease of man.     

An Efficient and Comprehensive Strategy for Genetic Diagnostics of Polycystic Kidney Disease

Renal cysts are clinically and genetically heterogeneous conditions. Autosomal dominant polycystic kidney disease (ADPKD) is the most frequent life-threatening genetic disease and mainly caused by mutations in PKD1. The presence of six PKD1 pseudogenes and tremendous allelic heterogeneity make molecular genetic testing challenging requiring laborious locus-specific amplification. Increasing evidence suggests a major role for PKD1 in early and severe cases of ADPKD and some patients with a recessive form. Furthermore it is becoming obvious that clinical manifestations can be mimicked by mutations in a number of other genes with the necessity for broader genetic testing. We established and validated a sequence capture based NGS testing approach for all genes known for cystic and polycystic kidney disease including PKD1. Thereby, we demonstrate that the applied standard mapping algorithm specifically aligns reads to the PKD1 locus and overcomes the complication of unspecific capture of pseudogenes. Employing careful and experienced assessment of NGS data, the method is shown to be very specific and equally sensitive as established methods. An additional advantage over conventional Sanger sequencing is the detection of copy number variations (CNVs). Sophisticated bioinformatic read simulation increased the high analytical depth of the validation study and further demonstrated the strength of the approach. We further raise some awareness of limitations and pitfalls of common NGS workflows when applied in complex regions like PKD1 demonstrating that quality of NGS needs more than high coverage of the target region. By this, we propose a time- and cost-efficient diagnostic strategy for comprehensive molecular genetic testing of polycystic kidney disease which is highly automatable and will be of particular value when therapeutic options for PKD emerge and genetic testing is needed for larger numbers of patients.     

Linkage confirms canine pkd1 orthologue as a candidate for bull terrier polycystic kidney disease

Bull terrier polycystic kidney disease (BTPKD) is a Mendelian disorder with many features reminiscent of human autosomal dominant polycystic disease, the latter disease being due to mutations at PKD1 and PKD2 loci. We investigated the role of the canine pkd1 orthologue in BTPKD via linkage analysis of a large kindred in which the disorder is segregating. Twelve microsatellite markers around the canine pkd1 locus (CFA6) were amplified from the genomic DNA of 20 affected and 16 unaffected bull terriers. An additional 28 affected dogs were genotyped at five key microsatellites. A highly significant multi-point LOD score that peaked over the canine pkd1 locus was observed (LOD = 6.59, best two-point LOD score LOD = 6.02), implicating this as the BTPKD locus.