Cell-free fetal DNA and intact fetal cells in maternal blood circulation: implications for first and second trimester non-invasive prenatal diagnosis

Both intact fetal cells as well as cell-free fetal DNA are present in the maternal circulation and can be recovered for non-invasive prenatal genetic diagnosis. Although methods for enrichment and isolation of rare intact fetal cells have been challenging, diagnosis of fetal chromosomal aneuploidy including trisomy 21 in first- and second-trimester pregnancies has been achieved with a 50-75% detection rate. Similarly, cell-free fetal DNA can be reliably recovered from maternal plasma and assessed by quantitative PCR to detect fetal trisomy 21 and paternally derived single gene mutations. Real-time PCR assays are robust in detecting low-level fetal DNA concentrations, with sensitivity of approximately 95-100% and specificity near 100%. Comparing intact fetal cell versus cell-free fetal DNA methods for non-invasive prenatal screening for fetal chromosomal aneuploidy reveals that the latter is at least four times more sensitive. These preliminary results do not support a relationship between frequency of intact fetal cells and concentration of cell-free fetal DNA. The above results imply that the concentration of fetal DNA in maternal plasma may not be dependent on circulating intact fetal cells but rather be a product of growth and cellular turnover during embryonic or fetal development.     

Chromosomal factors of infertility in candidate couples for ICSI: an equal risk of constitutional aberrations in women and men

To assess the frequency of chromosomal aberrations in French candidates for intracytoplasmic sperm injection (ICSI), and to explore the existence of a female chromosomal factor in some cases of couple infertility, a collaborative retrospective clinical and cytogenetic study was performed, launched by the Association des Cytogénéticiens de Langue Franciaise (ACLF). The karyotypes of 3208 patients [2196 men (68.4%), 1012 (31.6%) women] included in ICSI programmes over a 3-year period in France were collected. A total of 183 aberrant karyotypes was diagnosed, corresponding to an abnormality frequency of 6.1% (134/2196) for men and 4.84% (49/1012) for women. The following frequencies of abnormalities were observed respectively for men and women: 1.23% (n = 27) and 0.69% (n = 7) for reciprocal translocations, 0.82% (n = 18) and 0.69% (n = 7) for Robertsonian translocations, 0.13% (n = 3) and 0.69% (n = 7) for inversions, 3.32% (n = 73) and 2.77% (n = 28) for numerical sex chromosome aberrations, and 0.59% (n = 13) and 0% for other structural aberrations. Among the male patients of this latter group, 0.40% (n = 9) had a Y chromosome abnormality. Among the male patients with numerical sex chromosome abnormalities, 2.23% (n = 49) were 47,XXY, 0.32% (n = 7) were 47,XYY, and 0.77% (n = 17) had a mosaicism for numerical sex chromosome anomalies. All the female patients with sex chromosome abnormalities (2.77%, n = 28) had mosaicism for numerical sex chromosome anomalies. Even if these cases-the significance of which was sometimes questioned-were disregarded in the analysis, 2.08% (21/1012) of abnormal karyotypes remained in women. An overall increased frequency of chromosomal aberrations was found, and this confirmed that in some cases of poor reproductive outcome there may be a contribution of maternal chromosome aberrations. Indeed, the existence of a chromosome abnormality in the female partner was associated with the group of infertile men in which there was no apparent cause of infertility.     

The prognostic role of the extent of Y microdeletion on spermatogenesis and maturity of Sertoli cells

Substantial involvement of the Y chromosome in sexual development and spermatogenesis has been demonstrated. Over the last decade, varying extent of Y chromosome microdeletions have been identified among infertile patients with azoospermia or oligozoospermia. These microdeletions were clustered in three main regions named AZFa, AZFb, and AZFc. Analysis of the Y chromosome microdeletion was found to be of prognostic value in cases of infertility, both in terms of clinical management as well as for understanding the aetiology of the spermatogenesis impairment. However, the accumulated data are difficult to analyse, due to the variable extent of these deletions, the different sequence-tagged sites (STS) used to detect the microdeletions, and the non-uniformity of the histological terminology used by different investigators. This debate discusses the chances of finding testicular spermatozoa in men with a varying extent of Y chromosome microdeletions. The genotype and germ cell findings in men with AZFa microdeletions as well as those that include more than a single AZF region are reviewed, as is the effect of Y chromosome AZF microdeletions on the maturity of the Sertoli cells.     

香烟烟雾提取物致小鼠生殖细胞的遗传学损伤

目的：研究香烟烟雾提取物对小鼠生殖细胞染色体和精子的影响,方法：给雄性小鼠腹腔注射不同剂量的香烟烟雾提取物,观察其精原细胞染色体畸变及精子畸形的情况,结果：精原细胞染色体畸变率及精子畸形率均增高,精子畸形率增高的程度大于精原细胞染色体畸变率。结论：香烟烟雾提取物可致雄性小鼠生殖细胞染色体畸变和精子畸形。     

快杀灵对小鼠骨髓细胞的细胞毒性和遗传毒性检测

目的检测快杀灵是否具有细胞毒性和诱变性.方法按受试药物LD50的1/4×、1/2×、1×和2×四种不同剂量,分5次(间隔24小时)经口灌胃给小鼠染毒,然后用细胞遗传学方法,检测骨髓细胞的有丝分裂指数、染色体结构畸变率和畸变细胞率的变化.结果与阴性对照组比较,18.2mg/kg的剂量就使骨髓细胞的有丝分裂指数显著降低(P＜0.001).18.2mg/kg和36.4mg/kg剂量组的染色体结构畸变率和畸变细胞率有增高,但无显著性差异(P＞0.05),72.8mg/kg和145.6mg/kg剂量组的染色体结构畸变率和畸变细胞率均有显著增高(P＜0.01).结论快杀灵既可抑制细胞增殖,又可诱发染色体损伤.快杀灵对细胞增殖的抑制作用比对染色体的损伤作用更加强烈.     

常染色体嵌合变异的流行病学分布及其影响因素研究进展

人类体细胞突变的发生和积累,又称体细胞嵌合现象。其中,嵌合染色体变异（mCA）对基因组完整性的影响最为显著,被视为人类衰老的表型之一。随着全球人口老龄化进程的加速,了解mCA的人群流行病学分布及其影响因素,有助于探索人体衰老进程中“基因组失稳”及其相关生物学机制,为人类年龄相关疾病的一级预防提供科学依据。本文旨在汇总既往大规模人群研究结果,对外周血常染色体mCA的人群流行病学分布及其影响因素进行综述。     

Analysis of types of chromosomal aberrations following the combined action of chemical mutagens

Types of chromosomal aberrations in cultures of human lymphocytes exposed to the combined action of various concentrations of thiophosphamide and dipin, with different proportions of each, were studied. The mutagens acted on the G₀ stage. The range of concentrations used was from 3.17·10^–5 to 22.19·10^–5M. Equimolar concentrations of thiophosphamide inhibited more chromatid exchanges and fewer sister-strand (isolocus) unions than dipin, and it also induced a greater proportion of single breaks and a greater proportion of breaks in chromatid exchanges relative to the total number of chromosome breaks. Both the absolute and the relative frequencies of chromosomal aberrations depended on the concentration of the mutagens. A change in the ratio between thiophosphamide and dipin, if the total number of molecules of the two mutagens at the different concentration levels remained constant, gave rise to an effect whose level was between the effects of action of equimolar concentrations of the pure mutagens. This effect depended on the proportion of each mutagen in the combined treatment. It is concluded that the action of thiophosphamide and dipin is additive.Laboratory of Mutagenesis, Institute of Medical Genetics, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR A. V. Smol'yannikov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 85, No. 1, pp. 79–81, January, 1978.     

角膜波前像差引导的TransPRK和常规TransPRK矫正中度近视的疗效比较

目的 比较角膜波前像差引导(WFG)的经上皮准分子激光屈光性角膜切削术(TransPRK)和常规TransPRK矫正中度近视的疗效差异。方法 回顾性分析2021年1～12月在安徽省第二人民医院接受双眼TransPRK治疗的60例中度近视患者临床资料,根据是否采用WFG,分为WFG-TransPRK组(30例,60眼)和TransPRK组(30例,60眼)。在术前和术后6个月时,测量两组患者视力、屈光度、角膜高阶像差和中央角膜厚度等变量,记录两组患者术后6个月内的并发症发生情况,计算两组疗效指数和安全指数,并进行比较。结果 术前,两组等效球镜度、中央角膜厚度和角膜高阶像差比较,差异均无统计学意义(P>0.05)。TransPRK组手术前后总高阶相差和球差升幅高于WFG-TransPRK组(P<0.05),两组手术前后等效球镜度升幅、中央角膜厚度降幅比较,差异均无统计学意义(P>0.05)。随访6个月,两组疗效指数(t=1.913)、安全指数(t=0.775)和并发症发生率(χ²=0.162)比较,差异均无统计学意义(P=0.061、0.442、0....     

多环芳烃接触者染色体畸变和血清P21水平检测

目的 :了解多环芳烃接触者遗传指标和血清癌基因蛋白P2 1表达水平及其在肺癌早期诊断中的意义 ,为多环芳烃作业者的劳动保护提供科学依据。方法 :对接触多环芳烃化合物的焦炉工 2 4名、沥青工 2 7名和健康对照组 31名的染色体畸变率和血清癌基因蛋白P2 1水平进行了检测。结果 :染色体异常检出率 ,焦炉工和沥青工均显著高于对照组 (P <0 .0 0 5 ) ;染色体裂隙次数 ,焦炉工和沥青工均显著高于对照组 (P <0 .0 1) ;染色体结构、数目畸变数 ,焦炉工显著高于对照组 (P <0 .0 1)。血清P2 1水平 ,焦炉工、沥青工均显著高于对照组 (P <0 .0 5 ) ,沥青工显著高于焦炉工 (P <0 .0 5 )。结论 :多环芳烃化合物具有遗传毒性 ,并可致血清P2 1蛋白水平升高。     

1p36 deletion syndrome: Review and mapping with further characterization of the phenotype,a new cohort of 86 patients

Chromosome 1p36 deletion syndrome (1p36DS) is one of the most common terminal deletion syndromes (incidence between 1/5000 and 1/10,000 live births in the American population), due to a heterozygous deletion of part of the short arm of chromosome 1. The 1p36DS is characterized by typical craniofacial features, developmental delay/intellectual disability, hypotonia, epilepsy, cardiomyopathy/congenital heart defect, brain abnormalities, hearing loss, eyes/vision problem, and short stature. The aim of our study was to (1) evaluate the incidence of the 1p36DS in the French population compared to 22q11.2 deletion syndrome and trisomy 21; (2) review the postnatal phenotype related to microarray data, compared to previously publish prenatal data. Thanks to a collaboration with the ACLF (Association des Cytogénéticiens de Langue Française), we have collected data of 86 patients constituting, to the best of our knowledge, the second-largest cohort of 1p36DS patients in the literature. We estimated an average of at least 10 cases per year in France. 1p36DS seems to be much less frequent than 22q11.2 deletion syndrome and trisomy 21. Patients presented mainly dysmorphism, microcephaly, developmental delay/intellectual disability, hypotonia, epilepsy, brain malformations, behavioral disorders, cardiomyopathy, or cardiovascular malformations and, pre and/or postnatal growth retardation. Cardiac abnormalities, brain malformations, and epilepsy were more frequent in distal deletions, whereas microcephaly was more common in proximal deletions. Mapping and genotype–phenotype correlation allowed us to identify four critical regions responsible for intellectual disability. This study highlights some phenotypic variability, according to the deletion position, and helps to refine the phenotype of 1p36DS, allowing improved management and follow-up of patients.