一个致密核性先天性白内障家系致病基因的初步研究

目的 对一个致密核性先天性白内障家系的致病基因进行定位.方法 根据已报道的与先天性白内障相关基因的位置,选择紧密连锁的微卫星多态性标记,PCR扩增后进行基因分型,以分型结果为基础,利用等位基因共享分析和两点连锁分析对已知候选基因进行排除定位.结果 该家系临床表型为致密核性先天性白内障,目前尚无关于该表型致病突变的报道.已知的15个候选基因区域附近的微卫星位点均不存在等位基因共享;除D11S898外,其余27个微卫星位点的LOD值在重组率(θ)为0时均为-∝,致病基因与15个已知基因之间不存在连锁关系.结论 该家系的致病基因不是15个已知的先天性白内障相关基因,其致病基因有待进一步研究.     

常染色体显性遗传非综合征型耳聋致病基因的定位研究

目的应用连锁分析方法对一个常染色体显性遗传非综合征型耳聋（DFNA）家系进行耳聋基因的定位研究。方法通过进行家系调查、对家系成员进行全面查体及听力学检查，绘制遗传图谱。应用连锁分析的方法，首先排除此家系的遗传位点与表型相似的已知DFNA位点连锁，然后进行全基因组扫描。结果该家系致聋基因定位在2号染色体2q13-q14．2上，最大LOD值在D2S363处，为3．22。通过单倍型分析将遗传位点定位于微卫星标记D2S1888和D2S2224之间约8．4cM的区域。对区域内的候选基因PAX8进行突变筛查，没有发现突变。结论本家系的耳聋基因定位在一个新的DFNA位点上。     

4例与GJB2基因相关的遗传性耳聋家系的鉴别诊断

 目的 通过遗传学检测明确4例先天性耳聋家系的致病突变,并加以鉴别,针对性地给出诊疗意见。方法 选取2020-05至2022-01于北京妇产医院产前诊断中心遗传咨询门诊就诊的4例先天性耳聋家系。利用耳聋基因芯片、全外显子组测序的实验方法,明确其遗传学致病突变,并提供针对性的咨询意见。结果 4例遗传性耳聋均与GJB2基因相关,但存在不同情况。例1为常染色体显性掌跖角化病伴耳聋,其致病变异c.167T>C属新报道;例2中,夫妻双方分别为MYO7A与GJB2复合杂合突变导致的先天性耳聋,其中妻子携带2个新报道致病变异,即MYO7A: c.1214G>A和MYO7A: c.3545A>G;例3为GJB2复合杂合突变引起的常染色体隐性耳聋;例4为GJB2复合杂合突变导致的迟发性耳聋。结论 与GJB2基因相关的先天性耳聋具有较强的临床异质性,遗传检测是对其鉴别诊断的必要手段。     

常染色体显性遗传非综合征型耳聋家系的遗传学特征分析

目的 研究一个连续5代遗传的耳聋大家系(Z029家系),分析该家系的遗传学特征.方法 利用解放军总医院耳鼻咽喉研究所遗传性耳聋资源收集网络采集到一个5代遗传性耳聋大家系,对具有遗传信息的47例成员进行了全身系统检查及临床听力学检测,应用Cyrillic2.1软件构建家系图谱,分析该家系的遗传学特征.结果 Z029家系的表型表现为全频听力下降为主、迟发型的感音神经性耳聋,连续5代发病,男女成员均受累,每代患者的比率随着年龄增长具有逐渐增加的趋势,符合延迟显性的特征.结论 Z029家系是一个非综合征型常染色体显性遗传性耳聋大家系,其表型的外显率与年龄相关.该研究为进一步的致病基因定位与克隆奠定了基础,并为与年龄相关性耳聋分子病理机制的研究提供了模板.     

强直性肌营养不良临床及遗传特点分析

目的探讨强直性肌营养不良(DM)的临床及遗传特点,以提高对DM疾病的认识和诊断水平。方法对一DM家系确诊的5例患者临床资料进行收集及回顾性分析,包括患者基本资料、临床表现、血液生化、心电图、肌电图及肌肉活检等。收集完整的家系资料进行遗传分析。结果 5例DM患者临床均为慢性病程,以肌强直、肌无力、肌萎缩为主要表现,伴有眼部、心脏、内分泌和生殖、神经等多系统损害如白内障、心律失常、脱发、阳痿、习惯性流产、智能减退等,血清肌酶轻度增高或正常,肌电图具有特征性肌强直放电和肌源性损害,肌肉活检呈非特异性肌病特征。家系中男女均有发病,从第2代到第4代均有患者,每一代患病人数≥50%,发病年龄逐代提前。通过遗传分析判断出致病基因来源。结论 DM是一种以肌强直、肌无力、肌萎缩为主要表现的多系统损害的遗传性疾病,临床表现复杂多样。遗传方式符合常染色体显性遗传特点,具有遗传早现现象。识别DM的临床特点有助于提高对其认识和诊断水平。     

表皮松解性掌跖角化症家系基因突变研究

目的确定一个表皮松解性掌跖角化症家系的致病基因。方法收集该家系3例患者、3例表型正常个体和50名无亲缘关系的健康个体的外周血标本,抽提基因组DNA。选取角蛋白9(KRT9)基因邻近的3个STR多态性位点D17S1787、D17S579、D17S250进行连锁分析研究,并对KRT9基因所有外显子进行PCR扩增和Sanger测序分析。结果 3个STR位点均与患者表型共分离;患者的KRT9基因第1外显子均可见c.488 G>A(p.R163Q)杂合性突变,而家系中表型正常个体和50名正常对照个体均未检测到KRT9基因突变。结论 KRT9基因的c.488 G>A错义突变是导致该家系发生表皮松解性掌跖角化症的原因。     

中国人成人型多囊肾病PKD1基因突变筛选

成人型多囊肾病(Adult polycystic kidney dicease,APKD)是人类常见的常染色体显性遗传疾病,是8%～10%终末肾功能衰竭的病因.已知有3个基因的突变可导致APKD,其中PKD1和PKD2已被克隆和测序[1、2] ,PKD3也已定位[3].85%APKD是因PKD1基因突变所致,国外已发现近50种不同的突变方式[4].国内朱世乐等曾用与PKD1位点紧密连锁的微卫星DNA遗传标记,对中国人APKD家系成员作了单倍体型分析[5].本研究采用聚合酶链反应-单链构象多态性分析法(PCR-SSCP), 筛选分析了中国人APKD病人PKD1基因的突变.     

常染色体显性遗传Alport综合征的家系调查及免疫组化研究

目的：通过对一Alport综合征患者的家系调查、肾活检分析及免疫组化研究，明确其临床诊断，确定其遗传方式。方法：对患者3代以内的亲属共15例进行尿常规检查；对患者的肾活检标本进行病理检查；并运用抗Ⅳ型胶原的IgG、抗Ⅳ型胶原α3和α5链的IgG对患者的肾活检冰冻切片进行免疫组化研究。结果：经肾活检病理检查，进一步证实了Alport综合征的临床诊断，家属调查符合常染色体显性遗传，间接免疫荧光检查表明该患者肾小球基底膜上Ⅳ型胶原α2和α5链分布正常。结论：该Alport综合征家系的遗传方式符合常染色体显性遗传,常染色体显性遗传的Alport综合征肾小球基底膜上Ⅳ型胶原α3和α5链分布正常。     

强直性肌营养不良症一个家系的调查

强直性肌营养不良症是一种常染色体显性遗传疾病.本文报告一个家系的发病情况.家系调查及病例报告本家系中共12人,患者5例,其中男4例,女1例,病程2～29年,平均11.3年.此家系发病具有以下遗传特点:①连续2代发病;②第一代发病年龄为45岁,第2代为16～34岁,可见子代发病较亲代     

牛基因组研究进展（下）

３．５牛基因组遗传连锁图最近版本牛基因组遗传图报告的标记位点为１２５０个，其中有１２３６个多态ＤＮＡ标记，１４个红细胞抗体基因（ＥＡ）和血清蛋白多态。连锁图总长度２９９０ｃＭ，常染色体区内标记间平均间距为２．５ｃＭ。这个牛的第二代遗传连锁图为通过基因组扫描检测ＱＴＬ提供了有效的标记密度（Ｋａｐｐｅｓ等，１９９７）。ＣＳＩＲＯ的中等密度牛基因组遗传连锁图中ＤＮＡ多态标记为７４６个，其中６０１个微卫星标记，３１个连锁群（２８个常染色体，２个性染色体），连锁图总长度分别为：常染色体加平均性别３５３２ｃ…     

Genetic data from 15 STR loci for forensic individual identification and parentage analyses in UK domestic dogs (Canis lupus familiaris)

Eighteen STR loci and one sex determination locus present in the Finnzymes Canine 2.1 STR Multiplex Reagent Kit were screened in the UK dog population providing allele frequencies and population genetic parameters necessary for the application of STRs to forensic genetic casework. A total of 375 dogs were genotyped, including representative samples from each of twelve breeds used to evaluate Hardy-Weinberg equilibrium and calculate inter-population pairwise F(ST) values. Three loci were excluded from calculations of average random match probability due to deviations from Hardy-Weinberg Equilibrium or ambiguous genotyping. Random match probability based on fifteen STR loci and one sex locus was subsequently estimated to be 2.8 × 10(-17) for unrelated individuals across breeds.     

High autosomal STR allele sharing between full siblings

Multiplexes of polymorphic tetranucleotide Short Tandem Repeats (STRs) are regularly employed for forensic identification and kinship testing. If the DNA profiles of two samples match, there is a high probability that the samples have originated from the same individual. Match probabilities are calculated to evaluate the strength of DNA evidence. Relatives often share more alleles than unrelated individuals. High allele sharing among relatives can complicate source attribution of a DNA profile. In this paper, a case of high allele sharing of autosomal STR loci between two full siblings is reported and implications in source attribution are discussed.     

一个常染色体显性遗传非综合征性耳聋巨大家系调查

本文报道了一个遗传性非综合征性耳聋巨大家系。家族中有血缘关系的成员共有 113人。对有血缘关系的 6 6名家族成员及 8名配偶进行了全身体检、耳鼻咽喉专科检查、纯音测听、声导抗、听觉脑干诱发电位检查及血样采集。结果显示 ,6 6名家族成员中有 37人有不同程度的感音神经性听力下降 ,未见其他系统的异常改变 ;遗传图谱分析显示 ,该家系符合常染色体显性遗传特征。研究表明 ,对该家系听力资料和遗传资料的完整收集为下一步聋病基因定位克隆工作奠定了良好的基础。     

Inspecting close maternal relatedness: Towards better mtDNA population samples in forensic databases

Reliable data are crucial for all research fields applying mitochondrial DNA (mtDNA) as a genetic marker. Quality control measures have been introduced to ensure the highest standards in sequence data generation, validation and a posteriori inspection. A phylogenetic alignment strategy has been widely accepted as a prerequisite for data comparability and database searches, for forensic applications, for reconstructions of human migrations and for correct interpretation of mtDNA mutations in medical genetics. There is continuing effort to enhance the number of worldwide population samples in order to contribute to a better understanding of human mtDNA variation. This has often lead to the analysis of convenience samples collected for other purposes, which might not meet the quality requirement of random sampling for mtDNA data sets. Here, we introduce an additional quality control means that deals with one aspect of this limitation: by combining autosomal short tandem repeat (STR) marker with mtDNA information, it helps to avoid the bias introduced by related individuals included in the same (small) sample. By STR analysis of individuals sharing their mitochondrial haplotype, pedigree construction and subsequent software-assisted calculation of likelihood ratios based on the allele frequencies found in the population, closely maternally related individuals can be identified and excluded. We also discuss scenarios that allow related individuals in the same set. An ideal population sample would be representative for its population: this new approach represents another contribution towards this goal.     

Congenital vertical talus in four generations of the same family

Objective This paper presents four generations of a family with radiographically demonstrated congenital vertical talus (CVT) in whom a HOXD10 gene mutation was identified. Some members of the family with this mutation exhibited cavo-varus foot deformity consistent with a Charcot-Marie-Tooth (CMT)-like disorder.Design and patients Physical examination was performed on nearly all of the affected and unaffected family members. DNA was extracted from blood obtained from 14 subjects who showed radiographic and clinical features of CVT (two of whom also had CMT), from two subjects with features of CMT but not CVT, and from 20 related family members who were clinically normal.Results Radiographs show the appearance of uncorrected CVT in infancy, in childhood, and in adulthood. DNA analysis revealed a mutation in a HOXD10 gene located on chromosome 2 in all of the affected but none of the unaffected family members.Conclusion There is an autosomal-dominant-inherited mutation with complete penetrance which is found in all members of a pedigree with CVT, some of whom exhibit a CMT-like foot disorder. Radiologic findings vary depending on the severity of involvement, treatment provided and age of the patient.     

Maternity exclusion with a very high autosomal STRs kinship index

This paper reports a maternity testing case to assess the biological relationship between a woman and the boy she was adopting. For all 46 tested autosomal STR loci, the adopting woman and the boy shared at least one allele at each locus, which supported that the woman could be the biological mother of the boy. The pairwise kinship indices (KIs) were calculated for various identity-by-descent distributions. Motherson was the most likely relationship with a very high KI (i.e., 6.91E+08) based on 35 independent autosomal STR loci, but KIs of other pairwise relationships (e.g., aunt-nephew, full sib, etc.) were also high. Further testing of X-STRs and mtDNA excluded the maternity relationship between woman and boy, in which 13 out of 20 X-STR loci were inconsistent and 18 nucleotide mismatches were observed at hypervariable regions I and II of the mtDNA. However, a more distant relationship (e.g., aunt-nephew) cannot be excluded. This case reinforces that possible false identifications can occur in kinship analysis cases yielding very high KIs.     

Congenital fusion of the fourth and fifth metacarpals associated with primary gonadal failure

 Congenital fusion of the fourth and fifth metacarpals is described in a male infant and his maternal grandfather. Primary gonadal failure, which is present in the infant, has not been noted in previously reported cases. The pedigree in this family is compatible with X-linked recessive or autosomal dominant inheritance with incomplete penetrance.     

Evaluation of forensic genetic efficiency parameters of 22 autosomal STR markers (PowerPlex® Fusion system) in a population sample of Arab descent from Jordan

Jordan is a country located in the Middle East, on the East Bank of the Jordan River. In this study, the PowerPlex® Fusion (PPF) system was used to determine the allele frequencies and forensic efficiency parameters of 22 autosomal STR loci. Autosomal STR information was collected from the blood samples of 500 individuals belonging to the Jordanian population of Arab descent. The PPF system (Promega Corporation) was used to amplify the 22 autosomal STRs and the amplified samples were analysed on the 3130xl Genetic Analyser using GeneMapper ID-X 1.2 software (Applied Biosystems). All the autosomal STR loci met the requirements of the Hardy-Weinberg equilibrium after Bonferroni correction. This study revealed that the most informative locus among the 22 STR loci (excluding Amelogenin and DYS39) was Penta E locus (power of discrimination (PD) = 0.99), while the least informative locus was TPOX locus (PD = 0.834). The combined matching probability (MP) of the 22 loci was 1.9 × 10^?28. These forensic genetic parameters indicated the practicality of analysing these 22 STRs in forensic DNA identification and paternity testing among individuals from the Jordanian Arab population.