苦豆子不同居群染色体数目及核型分析

为了探讨苦豆子（Sophora alopecuroides）不同居群的染色体核型特征及进化关系,采用染色体常规压片技术分析了分布于内蒙古、甘肃、宁夏等6个自然地理居群的核型特征和进化趋势。结果显示：苦豆子6个居群的染色体数目恒定,均为2n=2x=36;染色体类型有中部着丝粒（m）和近中部着丝粒（sm）2种,除甘肃武威的居群3含有sm型染色体外,其余居群的染色体均为m型;染色体平均臂比为1.19～1.37,长度比介于1.72～2.19,核型不对称系数处于54.30%～57.17%;核型类型有1A、3A和2B三种;苦豆子居群3的核型不对称系数最大,进化程度较高,居群19（内蒙古鄂尔多斯）的核型不对称系数最小,进化程度较低。聚类分析显示,苦豆子6个参试居群聚集成A和B两大分支,分支A又可分为C和D两亚支,其中居群5（甘肃武威）和居群13（内蒙古阿拉善盟）聚为C亚支,亲缘关系较近,居群3单独聚为D亚支,与C亚支两居群的亲缘关系相对较远;分支B又可分为E和F两亚支,居群19和居群43（内蒙古鄂尔多斯）聚为E亚支,亲缘关系较近,居群17（宁夏银川）单独聚为F亚支,与E亚支两居群的亲缘关系相对较远。...     

毛冠鹿种内异染色质变化与染色体多态

采用原代和传代培养方法对8头毛冠鹿(Elaphodus cephalophus)的皮肤细胞进行了染色体研究,发现了一种核型与以前所报道的几种核型不一致,确定为一新核型。在该核型中,染色体众数2n=47,2条X染色体异型,一条为端着丝粒,另一条为近端着丝粒。C-带显示该核型中异染色质除了分布在2条X染色体长臂中之外,在第一对大的端着丝粒染色体中的一条近着丝粒区出现一异染色质“柄”。结合C-带及薄层扫描结果对毛冠鹿种内常染色体、性染色体中异染色质的含量和分布与染色体多态的关系进行了探讨。     

Indispensable function of the germ nucleus for postconjugational stomatogenesis in Paramecium caudatum: Evidence against its genic function shown by hypohaploid micronuclei

It is known that the germinal micronucleus at the stages of gametogenesis and/or fertilization has an indispensable function for the postconjugational development of oral apparatus (stomatogenesis) in Paramecium caudatum. To determine whether this function is due to some specific genes in the micronucleus, postconjugational stomatogenesis was examined in the conjugation of haploid and hypohaploid cells. Haploid clones were obtained by conjugation between amicronucleate cells and diploid micronucleate cells. After conjugation between these haploid clones or between the haploid clones and amicronucleate clones, we succeeded in obtaining hypohaploid clones that have various types of nullisomic micronuclei. If a few genes in the micronucleus control postconjugational stomatogenesis, some hypohaploid micronuclei should undergo stomatogenesis normally, but others should not. In the present work, however, almost all the hypohaploid micronuclei developed the oral apparatus and formed food vacuoles. We can apparently rule out the possibility that a few specific genes of the micronucleus are required for postconjugational stomatogenesis in Paramecium caudatum, unless selection operates to retain the chromosomes with the essential gene(s). Dev. Genet. 23:142–150, 1998. © 1998 Wiley-Liss, Inc.     

Current status and future prospects of array-based comparative genomic hybridisation.

The majority of human cancers as well as many developmental abnormalities harbour chromosomal imbalances, many of which result in the gain and/or loss of genomic material. Conventional comparative genomic hybridisation (CGH) has been used extensively to map DNA copy number changes to chromosomal positions. The introduction of microarray CGH provided a powerful tool to precisely detect and quantify genomic aberrations and map these directly onto the sequence of the human genome. In the past several years, a number of different approaches towards array-based CGH have been undertaken. This paper reviews these approaches and presents some of the recently-developed applications of this new technology in both research and clinical settings.     

International study of factors affecting human chromosome translocations

Chromosome translocations in peripheral blood lymphocytes of normal, healthy humans increase with age, but the effects of gender, race, and cigarette smoking on background translocation yields have not been examined systematically. Further, the shape of the relationship between age and translocation frequency (TF) has not been definitively determined. We collected existing data from 16 laboratories in North America, Europe, and Asia on TFs measured in peripheral blood lymphocytes by fluorescence in situ hybridization whole chromosome painting among 1933 individuals. In Poisson regression models, age, ranging from newborns (cord blood) to 85 years, was strongly associated with TF and this relationship showed significant upward curvature at older ages versus a linear relationship (p < 0.001). Ever smokers had significantly higher TFs than non-smokers (rate ratio (RR) = 1.19, 95% confidence interval (CI), 1.09–1.30) and smoking modified the effect of age on TFs with a steeper age-related increase among ever smokers compared to non-smokers (p < 0.001). TFs did not differ by gender. Interpreting an independent effect of race was difficult owing to laboratory variation. Our study is three times larger than any pooled effort to date, confirming a suspected curvilinear relationship of TF with age. The significant effect of cigarette smoking has not been observed with previous pooled studies of TF in humans. Our data provide stable estimates of background TF by age, gender, race, and smoking status and suggest an acceleration of chromosome damage above age 60 and among those with a history of smoking cigarettes.     

Association analysis of the RGS4 gene in Han Chinese and Scottish populations with schizophrenia

We investigated the RGS4 as a susceptibility gene for schizophrenia in Chinese Han (184 trios and 138 sibling pairs, a total of 322 families) and Scottish (580 cases and 620 controls) populations using both a family trio and case-control design. Both the samples had statistical power greater than 70% to detect a heterozygote genotype relative risk of >1.2 for frequent RGS4-risk alleles. We genotyped four single nucleotide polymorphisms (SNPs) which have previously been associated with schizophrenia as either individually or part of haplotypes. Allele frequencies and linkage disequilibrium between the SNPs was similar in the two populations. In the Chinese sample, no individual SNPs or any of their haplotypes were associated with schizophrenia. In the Scottish population, one SNP (SNP7) was significantly over-represented in the cases compared with the controls (0.44 vs. 0.38; A allele; chi(2) 7.08, P = 0.011 after correction for correlation between markers by permutation testing). One two-marker haplotype, composed of alleles T and A of SNP4 and SNP7, respectively, showed individual significance after correction by permutation testing (chi(2) 6.8; P = 0.04). None of the full four-marker haplotypes showed association, including the G-G-G-G haplotype previously associated with schizophrenia in more than one sample and the A-T-A-A haplotype. Thus, our data do not directly replicate previous associations of RGS4, but association with SNP 7 in the Scottish population provides some support for a role in schizophrenia susceptibility. We cannot conclusively exclude RGS4, as associated haplotypes are likely to be surrogates for unknown causative alleles, whose relationship with overlying haplotypes may differ between the population groups. Differences in the association seen across the two populations could result from methodological factors such as diagnostic differences but most likely result from ethnic differences in haplotype structures within RGS4.     

Drosophila cohesins DSA1 and Drad21 persist and colocalize along the centromeric heterochromatin during mitosis

Sister chromatid cohesion in eukaryotes is maintained mainly by a conserved multiprotein complex termed cohesin. Drad21 and DSA1 are the Drosophila homologues of the yeast Scc1 and Scc3 cohesin subunits, respectively. We recently identified a Drosophila mitotic cohesin complex composed of Drad21/DSA1/DSMC1/DSMC3. Here we study the contribution of this complex to sister chromatid cohesion using immunofluorescence microscopy to analyze cell cycle chromosomal localization of DSA1 and Drad21 in S2 cells. We observed that DSA1 and Drad21 colocalize during all cell cycle stages in cultured cells. Both proteins remain in the centromere until metaphase, colocalizing at the centromere pairing domain that extends along the entire heterochromatin; the centromeric cohesion protein MEI-S332 is nonetheless reported in a distinct centromere domain. These results provide strong evidence that DSA1 and Drad21 are partners in a cohesin complex involved in the maintenance of sister chromatid arm and centromeric cohesion during mitosis in Drosophila.     

Stabilization of macromolecular chromatin complexes in mitotic chromosomes by light irradiation in the presence of ethidium bromide

A method was developed for stabilizing mitotic chromosomes. Light irradiation of permeabilized cells in a low concentration of ethidium bromide made chromatin resistant to high salt concentrations and decondensing buffer. This resistance was abolished by proteinase treatment, but not by DNase or RNase treatment. In photostabilized and extracted chromosomes, chromatin appeared as thick fibers with discrete high electron density regions. These stabilized structures might correspond to the higher-level structures (chromonemata) observed in native chromatin. Moreover, the electron density was higher in the centromeric regions than the chromosome arm material. Thus, the method allows chromatin substructures (chromonemata and centromeric heterochromatin) to be stabilized inside mitotic chromosomes.     

Polymerase chain reaction method to identify Down syndrome model segmentally trisomic mice

The Ts65Dn segmentally trisomic mouse possesses an extra copy of a segment of chromosome 16 translocated to chromosome 17. This segment includes the mouse homolog of the Down syndrome critical region of human chromosome 21. The Ts65Dn mouse serves as a useful model to study the developmental regulation of the Down syndrome phenotype. To identify mice bearing the extra chromosome 16 segment, we developed a polymerase chain reaction (PCR) method as an alternative to karyotyping. Conditions under which segments of genes on chromosome 16 (App and Dyrk1a) could be coamplified with a control gene on chromosome 8 (Acta1) so that the yield of each PCR product was proportional to the amount of its template were determined. The amplification products were resolved and quantified by two methods. In the first method, the DNA segments were separated by agarose gel electrophoresis and stained with ethidium bromide. The fluorescence yields were quantified by photodensitometry. In the second method, the fragments were resolved and quantified by the high-performance DNA analysis system, a high-throughput, multichannel, microcapillary electrophoresis instrument. The results of both methods were within 10% of the expected ratio of 1.5. Application of these methods has allowed the maintenance of a Ts65Dn breeding colony through six generations and should permit the precise and efficient identification of trisomic and disomic animals at any developmental stage with minimally invasive procedures.     

DSCR1 (ADAPT78) lethality: evidence for a protective effect of trisomy 21 genes?

Over the last several years, suggestive evidence has accrued supporting a possible involvement for DSCR1 (ADAPT78) in Down syndrome. Toward testing this, we attempted to generate DSCR1 transgenic mice. Surprisingly, in almost every case, embryonic lethality was observed. In C57Bl/6 mice, DSCR1 human transgene was identified in developing embryos prior to lethality and up to day 9.5. Its mRNA expression was also observed and varied relative to control. In rare instances (twice) where transgenics survived to term, no mRNA expression was observed, suggesting that expression is required for lethality. This lethal phenotype contrasted with, and was surprising in light of, mouse models of Down syndrome where multiple chromosome 21 genes including Dscr1 are overexpressed and survive to term. To explain the seemingly contradictory lethal effect of DSCR1 by itself but not in combination with other trisomy genes, we propose that some trisomy genes (including DSCR1) confer lethality, but others suppress it.