A Dutch family with progressive sensorineural hearing impairment linked to the DFNA2 region

We studied a Dutch family with DFNA2-linked progressive sensorineural hearing impairment (SNHI). Recent audiograms were obtained from 18 of the affected persons (age 7–81 years) and were used in a gene-linkage analysis. Linear regression analysis of the audiograms, using binaural mean thresholds, disclosed on average a descending slope of approximately 10 dB/octave at any age and an annual threshold increase at any frequency of about 0.7 dB/year. There may have been substantial congenital impairment at higher frequencies, but longitudinal analysis of hearing impairment in the youngest case, who was followed from age 5 years, suggested that the most significant changes in hearing may have occurred in the first two decades of life. Linkage analysis was carried out with special attention to the DFNA2 region because hearing trends were very similar to families previously linked to DFNA2. Linkage to DFNA2 was established with maximum lod scores of 4.7 and 3.2 for the flanking markers of the DFNA2 region (D1S432;MYCL1). Received: 25 February 1999 / Accepted: 11 June 1999     

大肠癌新相关基因HSU17714的染色体定位研究

目的确定大肠癌新相关基因ＨＳＵ１７７１４的染色体定位。方法采用强化荧光原位杂交技术（ＦＩＳＨ）,以生物素化酪胺强化荧光原位杂交信号。结果８０．０％（１２８／１６０）的间期细胞和５９．８％（１０４／１７４）的中期分裂相可见到明显集中的ＨＳＵ１７７１４基因的杂交信号,相应荧光Ｒ带分析中,８５．１％（４０／４７）在２２号染色体上１区３带处有杂交信号。结论ＨＳＵ１７７１４基因定位于２２ｑ１３。     

喉癌中13号染色体杂合性丢失研究

目的　为初步限定喉癌中 13号染色体抑癌基因的缺失区域和为发现及定位抑癌基因提供线索和依据。方法　应用聚合酶链反应 ( PCR) ,筛查了 58例喉癌 (包括 3例原位癌 )组织中染色体13q上 D13S765( 13q13) ,RB1.2 0 ( 13q14.2 ) ,D13S133( 13q14.3) ,D13S318( 13q2 1) 4个座位微卫星多态标记的杂合性丢失。结果　 3例原位癌中无一例发生 13q的杂合性丢失 ,55例浸润癌中在 13q一个以上座位出现杂合性丢失的频率为 4 5% ( 2 4 / 53) ,D13S765座位的杂合性丢失的频率最高 ,为 52 %( 2 2 / 4 2 )。结论　喉癌组织中染色体 13q缺失区域在 D13S765( 13q13)座位附近 ,RB1的近端 ,即在D13S765座位附近存在着与喉癌发生发展密切相关的抑癌基因 ,可能包括 RB1基因 ,它的失活与浸润期喉癌发生发展密切相关。     

Cytogenetic abnormalities related to histopathologic grade of astrocytic tumors

Cytogenetic analysis was performed on 7 lowgrade astrocytomas, 10 anaplastic astrocytomas, and 14 glioblastomas. Abnormal chromosome numbers were noted in all cases of high-grade astrocytomas but were rarely noted in low-grade astrocytomas (28%). The most consistent changes in high-grade astrocytomas were complete loss of chromosome 10 (61%), gain of chromosome 7 (56%), and loss of chromosome 17 (28%). Certain structural abnormalities, such as marker chromosomes and double minutes (33%), and the deletion and translocation of chromosomes 1 (33%) and 17 (17%), were also noted. These results indicate that changes in the number and/or structure of chromosomes with related inactivation of tumor suppressor gene or oncogene activation might play a critical role in the formation and anaplastic progression of astrocytic tumors.     

钝顶螺旋藻抗突变作用的研究

对钝顶螺旋藻的抗突变作用进行了研究。结果表明：钝顶螺旋藻在２０００ｍｇ／ｋｇ剂量下,对环磷酰胺所致小鼠骨髓细胞微核增加有拮抗作用（Ｐ＜０．０５）,对丝裂霉素所致小鼠睾丸染色体畸变在染色体畸变细胞率指标上具有拮抗作用（Ｐ＜０．０５）,在性染色体单价体,常染色体单价体,具有拮抗趋势,但无统计学意义（Ｐ＞０．０５）。在６７,６７０ｍｇ／ｋｇ两个低剂量下,对环磷酰胺所致小鼠骨髓细胞微核和对丝裂霉素所致小鼠睾丸染色体畸变在染色体畸变细胞率增高的拮抗作用无统计学差异（Ｐ＞０．０５）。     

Physical mapping of the MEL gene family in Saccharomyces cerevisiae

Nine members, MEL2–MEL10, of the MEL gene family coding for -galactosidase were physically mapped to the ends of the chromosomes by chromosome fragmentation. Genetic mapping of the genes supported the location of all the MEL genes in the left arm of their resident chromosomes.     

Evaluating the mutagenic potential of chemicals the minimal battery and extrapolation problems

During the past ten years growing concern about damage to DNA as an important cause of human ill-health has resulted in an explosive development of the field of genetic toxicology. Adequate regulations to restrict exposure to chemical mutagens require recognition and evaluation of mutagenic activity. For this purpose a qualitative and an extrapolation phase can be distinguished. For the qualitative phase, the minimal battery should consist of at least three tests, that is: (1) tests for gene- or point mutations in bacteria (Salmonella or E. coli) with and without metabolic activation; (2) two tests for point mutations in eukaryotes, or (3) one such test and a test for the detection of chromosome aberrations in mammalian cells in vitro. Depending on experience and facilities, a choice of two can be made out of the following four test systems: (1) Tests for point mutations in mammalian cells in vitro, with and without metabolic activation (deficiency for HGPRT, or TK); (2) the sex-linked recessive lethal test with Drosophila melanogaster; (3) tests with yeast, Saccharomyces cerevisiae, for point mutations, with and without metabolic activation; (4) tests for chromosome aberrations in mammalian cells in vitro, with and without metabolic activation. Two different metabolic activation systems should be employed. For further selection of more sensitive test systems, studies on comparative mutagenesis are considered important. A mammalian test for chromosome aberrations in vivo is not included in this minimal battery. Since under in vivo conditions considerably lower concentrations have to be employed than in vitro, it seems unlikely that positive results will be obtained with an in vivo mammalian cytogenetic assay, following negative results in an in vitro cytogenetic assay or in two different tests for point mutations. The finding that the effective concentration for the production of chromosome breakage events differs from that required to induce point mutations (the two-level effect) will be briefly discussed. When mutagenic compounds are indispensible or, in the case of ubiquitous exposure, a quantification of risks becomes necessary and here one is confronted with many difficulties. Information on damage that is hard to measure directly can be obtained in an indirect way by comparison with end-points that can be determined experimentally, such as alkylation per nucleotide. Names of chemical substances tested: hydroxylamine; diepoxybutane; N-ethyl-N-nitrosourea; methylmethanesulfonate (MMS); DEN; Mitomycin C; Procarbazine; atrazine; benz(a)pyrene; EMS; pyrolitic products; flavonoids; mycotoxins; nitrosamines; TEMGiven at the International Conference Mutagenicity Testing of Pharmaceuticals: Present Status, Paris, 12–14 March, 1980, sponsored by the Fondation de l'Industrie Pharmaceutique pour la Recherche     

胃癌7号染色体长臂的杂合性缺失分析

目的:检测胃癌患者7号染色体长臂微卫星位点的杂合性缺失(loss of heterozygosity,LOH),以初步确定7号染色体长臂上与胃癌相关基因连锁最密切的微卫星多态位点及LOH的临床意义.方法:在70例原发性胃癌中应用多重PCR技术扩增覆盖整个7号染色体长臂的9个微卫星位点(平均遗传距离为10cm),聚丙烯酰胺凝胶电泳分离PCR产物,用GeneScan、Genotyper软件进行分析.结果:9个微卫星位点的LOH均可发生于原发性胃癌,总的LOH频率为34.3%(24/70),其中D7S486和D7S798位点的LOH频率较高,分别为24.0%(12/50)和19.2%(5/26);总的LOH频率随临床分期而显著增高(P=0.046),D7S486位点的LOH频率在淋巴结转移者显著高于无淋巴结转移者(P=0.015).结论:在7号染色体长臂D7S486和D7S798位点附近,可能存在与胃癌发展相关的抑癌基因.     

海洛因依赖者在第19、20、21和22号染色体上的易感基因位点的分析

目的:筛查海洛因依赖者在第19、20、21和22号染色体上的易感基因的位点.方法:对10例海洛因依赖者和其正常同胞对照者的第19、20、21和22号染色体进行以短串联重复序列(short tandem repeats,STR)为遗传标记的基因扫描分析.结果:D20S195和D22S423位点的等位基因在海洛因依赖组和其正常同胞对照组之间分布有显著性差异(P＜0.05),其它STR位点的等位基因在海洛因依赖组和其正常同胞对照组之间分布没有显著性差异(P＞0.05).结论:D20S195和D22S423位点附近可能存在海洛因依赖的易感基因.     

人原发性大肠癌的染色体分析

用改良的直接法分析了20例大肠癌新鲜瘤组织及4例大肠癌细胞系的细胞遗传学改变，发现瘤细胞多为异倍体，染色体众数以亚二倍体居多；核型分析发现，其杂色体数目畸变为，13号染色体增多；17号、1号和Y染色体的丢失，结构畸变最常累及1号染色体，断裂声、1q21出现率较高，其次为1p13区的断裂及末端丢失。提示1号染色体结构异常可能为原发性大肠癌特征性染色体改变之一。