电离辐射诱发的联会复合体畸变研究

以雄性昆明种小鼠为实验材料，Ｘ射线一次全身均匀照射，照后不同时间取材，分别用电子显微镜观察精母细胞前期联会复合体畸变和光镜观察中期Ⅰ染色体畸变。结果表明，和中期Ⅰ染色体畸变相比，联会复合体的畸变类型更复杂，其发生频率也明显增高；回归分析表明，两者多价体发生率均随剂量增加而增加，剂量与多价体发生率之间的关系符合直线方程，Ｙｓｃ＝－０．８６＋１．６８Ｄ（ｒ＝０．９３）ＹＤ－ＭＩ＝－０．２０＋０．９０Ｄ（ｒ＝０．９９），说明联会复合体分析可以更敏感地检测畸变。因此，利用联会复合体检测技术来估价电离辐射对哺乳动物潜在的遗传危害优于常规染色体畸变分析。     

Refined mapping and characterization of the recessive familial amyotrophic lateral sclerosis locus (ALS2) on chromosome 2q33

Amyotrophic lateral sclerosis (ALS) is a progressive degenerative neuromuscular disease that shows familial, autosomal dominant inheritance in 10%–15% of cases. Previous genetic analysis of one large family linked a recessive form of familial ALS (FALS-AR type 3) to the chromosome 2q33–35 region. Using additional polymorphic markers, we have narrowed the size of the linked region to approximately 1.7 cM by linkage and haplotype analysis. We have also established a yeast artificial chromosome contig across the locus that covers an approximate physical distance of 3 million bases. Based on this contig, genes and expressed sequences that map near the 2q33 region have been examined to determine whether they are located within this ALS2 candidate locus. Five identified genes and 34 expressed sequence tags map within the region defined by crossover analysis and merit further consideration as candidate genes for this disease. Accepted: July 15, 1998 / Published online: October 28, 1998     

Molecular characterization of an unusual variant of the short arm of chromosome 15 by FISH-technique

Summary One of the most frequent translocations involving the long arm of chromosome Y with autosomes is with the short arm of chromosome 15. The regions which are involved in this translocation fluoresce brightly, are highly heteromorphic and thus escape detection. Therefore, these abnormalities could not be fully characterized, especially in cases where parents are not available or paternity is disputed. Results from the employment of the selective staining techniques DA/DAPI and Q-banding have been inconclusive. FISH-technique using whole chromosome painting (WCP) probes should be used to decipher such translocations. We present a case where, even after using a battery of probes, the origin of extra material on chromosome 15p could not be identified though it was not a part of Yq.     

低氧、紫外线对小鼠微核率的影响

本文采用小鼠淋巴细胞微核测定技术,对不同海拔高度(平原(46m)、中度海拔(2260m)、特高海拔(模拟6000m)、不同紫外线强度(大、小剂量)照射和减压6000m加紫外线照射的NIH系小白鼠进行了微核测定。结果表明:随着低氧程度的加重和紫外线照射强度的增加,都可使小鼠微核率显著增高;而且低氧加紫外线双重因素作用对小鼠微核率的影响具有协同作用。说明强烈的紫外线和低氧可诱发机体染色体畸变,且二者似科有协同致畸作用。揭示我们不能轻视高原紫外线对机体的损伤,应加强综合防护。     

Molecular characterization of the 7q deletion in myeloid disorders

Deletion of the long arm of chromosome 7 is a common karyotypic finding in myeloid disorders and in particular is found in association with secondary leukaemias. We have used restriction fragment length polymorphisms and gene dosage experiments to assess the loss or retention of sequences localized to chromosome 7q in five patients with clonal myeloid disorders and a 7q deletion. The deletion was interstitial in all cases with retention of the anonymous marker pS194 located at 7q36-qter. Three out of five cases also retained the more proximal gene T-cell receptor β (TCRβ) located at 7q35. The proximal breakpoints of all five cases were localized to 7q22 by cytogenetic analysis. In two cases the proximal breakpoint lay between the genes for elastin (ELN) and collagen type 1α (COL1A2) and in three cases distal to this region between the genes for erythropoietin (EPO) and acetylcholinesterase (ACHE). The genes for ACHE, plasminogen activator inhibitor 1 (PLANH1), CCAAT displacement protein (CUTL1) and Met proto-oncogene (MET) were deleted in all cases. Molecular analysis of the 7q deletion in myeloid leukaemias demonstrates heterogeneity of the breakpoints, supporting a recessive mechanism of tumourigenesis.     

酒精依赖患者戒酒前后平均微核细胞频率的改变

[目的 ]探讨酒精依赖患者体内的酒精对遗传物质的损伤及戒酒对其控制修复的影响 .[方法 ]应用外周血淋巴细胞培养方法 ,检测微核细胞频率 .使用自身对照研究方法 ,对酒精依赖患者戒酒前、后的MNCF差值进行比较 ,并对MNCF与饮酒年限、饮酒总量的关系进行相关性分析 .[结果 ]酒精依赖患者的MNCF明显高于正常对照组 ;戒酒后MNCF呈下降趋势 ;MNCF的增高与饮酒年限、饮酒总量呈正相关性 .[结论 ]酒精依赖患者体内出现遗传物质的损伤 ,这种损伤可通过戒酒治疗可逆恢复     

Analysis of human HPRT deletion mutations with X-linked probes and pulsed field gel electrophoresis.

Because the human hprt gene is used in numerous mutation studies, it is important to fully characterize this gene. Therefore, our laboratory has undertaken to map the region around the hprt gene at band q26 of the human X chromosome. Utilizing hprt mutant T-cell clones isolated using the hprt clonal assay, which have deletions of all or part of the hprt gene, we have ordered 5 anonymous probes previously known to map in Xq26. Results suggest that this region includes between 460 kb and 18 Mb of DNA, which is at least 10 times the size of the hprt gene itself (43 kb). Pulsed field gel analysis of the region is underway to determine the exact distances between each of the anonymous probes and hprt and to determine deletion sizes in the mutant T-cell clones.     

Association between HLA-A1 allele and schizophrenia gene(s) in patients refractory to conventional neuroleptics but responsive to clozapine medication

Abstract: We report an association between HLA-A1 allele and a subgroup of schizophrenic patients refractory to conventional neuroleptic treatment but responsive to clozapine. The frequency of HLA-A1 was 58% among the schizophrenic patients not responding to conventional treatment but responsive to clozapine but only 10.5% among the patients responding to conventional neuroleptics. The HLA-A1 occurs in 20% of the random Finnish population. Our results indicate that HLA-A1 defines a subgroup of schizophrenic patients with a selective response to neuroleptics.     

Papillary renal cell carcinoma with clear cell cytomorphology and chromosomal loss of 3p

AIMS: Cytogenetic studies on renal cell carcinomas (RCCs) have disclosed a correlation between chromosome aberrations and histomorphological features. Nevertheless, it is still controversial whether the cytomorphology of the tumour cells (clear cell, chromophilic, chromophobe) or their growth pattern (nonpapillary, papillary) is more discriminative for the combined histomorphological-cytogenetic classification of RCCs. METHODS AND RESULTS: Three RCCs with papillary growth pattern and clear cell cytomorphology were analysed by classical cytogenetics using standard G-banding techniques. Each tumour displayed clonal aberrations leading to loss of terminal 3p chromosomal segments. Monosomy 14 was also consistently found. Trisomy 17 was not observed in any of the tumours. CONCLUSIONS: This series of three RCCs consisting of clear cells with papillary architecture revealed chromosomal aberrations characteristic for the conventional (clear cell) RCC. Irrespective of the predominant papillary growth pattern, none of the cases were characterized by trisomy of chromosomes 3q, 7, 8, 12, 16, 17 and 20 and loss of Y chromosome which are widely regarded as the most consistent genetic alterations for papillary RCC. Therefore, our cytogenetic findings provide evidence that papillary clear cell RCCs should be classified according to their cytomorphology rather than their growth pattern even when papillary architecture is prominent.     

Chromosome 22q11 microdeletion and congenital heart disease – a survey in a paediatric population

Congenital heart disease is a common finding in patients with microdeletion of chromosome 22q11. To determine if the deletion is an epidemiologically important cause of congenital heart disease, we studied a consecutive series of children attending a paediatric cardiac clinic and of neonates diagnosed as having structural congenital heart disease. Venous blood samples were tested by fluorescent in-situ hybridisation analysis for microdeletion of chromosome 22q11 using probe D22S75. Each patient was examined for the other clinical features associated with microdeletion of chromosome 22q11, and any family history of congenital heart disease recorded. Of 151 families approached, 111 participated and a fluorescent in-situ hybridisation result achieved in 87. One patient with microdeletion of chromosome 22q11 was identified; the clinical features were those of DiGeorge syndrome. Two patients with CHARGE association, two with nasal speech, ten with high arched palate, and 15 with minor facial dysmorphic features had no deletion. Conclusion Microdeletion of chromosome 22q11 detected by probe D22S75 is rare in this consecutive series of patients with structural congenital heart disease. Received: 31 January 1998 / Accepted in revised form: 24 September 1998