一例45,XO/46,X,i(Xq)嵌合型Turner′s综合征及其细胞遗传学分析

本文描述了一种少见的嵌合型Turner′s综合征。细胞遗传学检查证明:患者一个细胞系为45,XO,约占95％;另一个细胞系为46,X,i(Xq)约占5％。与典型Turner′s综合征相比较,分析了该患者染色体核型与表型的关系,讨论了Lyon关于两个X染色体之一随机失活的观点和异常核型产生的原因。     

Chromodomains are protein-RNA interaction modules

In Drosophila, compensation for the reduced dosage of genes located on the single male X chromosome involves doubling their expression in relation to their counterparts on female X chromosomes. Dosage compensation is an epigenetic process involving the specific acetylation of histone H4 at lysine 16 by the histone acetyltransferase MOF. Although MOF is expressed in both sexes, it only associates with the X chromosome in males. Its absence causes male-specific lethality. MOF is part of a chromosome-associated complex comprising male-specific lethal (MSL) proteins and at least one non-coding roX RNA. How MOF is integrated into the dosage compensation complex is unknown. Here we show that association of MOF with the male X chromosome depends on its interaction with RNA. MOF specifically binds through its chromodomain to roX2 RNA in vivo. In vitro analyses of the MOF and MSL-3 chromodomains indicate that these chromodomains may function as RNA interaction modules. Their interaction with non-coding RNA may target regulators to specific chromosomal sites.     

Parental imprinting of the mouse H19 gene.

THE mouse H19 gene encodes one of the most abundant RNAs in the developing mouse embryo. It is expressed at the blastocyst stage of development, and accumulates to high levels in tissues of endodermal and mesodermal origin (H. Kim, unpublished result). After birth the gene is expressed in all tissues except skeletal muscle. It lacks a common open reading frame in the 2.5-kilobase RNA, but has considerable nucleotide sequence similarity between the genes of rodents and humans. Expression of the gene in transgenic mice results in late prenatal lethality, suggesting that the dosage of its gene product is strictly controlled. The H19 gene maps to the distal segment of mouse chromosome 7, in a region that is parentally imprinted, a process by which genes are differentially expressed on the maternal and paternal chromosomes. We have now used an RNase protection assay that can distinguish between H19 alleles in four subspecies of Mus, to demonstrate that the H19 gene is parentally imprinted, with the active copy derived from the mother. This assay will be of general use in assaying allele-specific gene expression.     

Characterization of a murine gene expressed from the inactive X chromosome

In mammals, equal dosage of gene products encoded by the X chromosome in male and female cells is achieved by X inactivation. Although X-chromosome inactivation represents the most extensive example known of long range cis gene regulation, the mechanism by which thousands of genes on only one of a pair of identical chromosomes are turned off is poorly understood. We have recently identified a human gene (XIST) exclusively expressed from the inactive X chromosome. Here we report the isolation and characterization of its murine homologue (Xist) which localizes to the mouse X inactivation centre region and is the first murine gene found to be expressed from the inactive X chromosome. Nucleotide sequence analysis indicates that Xist may be associated with a protein product. The similar map positions and expression patterns for Xist in mouse and man suggest that this gene may have a role in X inactivation.     

Differential activity of maternally and paternally derived chromosome regions in mice

Although both parental sexes contribute equivalent genetic information to the zygote, in mammals this information is not necessarily functionally equivalent. Diploid parthenotes possessing two maternal genomes are generally inviable, embryos possessing two paternal genomes in man may form hydatidiform moles, and nuclear transplantation experiments in mice have shown that both parental genomes are necessary for complete embryogenesis. Not all of the genome is involved in these parental effects, however, because zygotes with maternal or paternal disomy for chromosomes 1, 4, 5, 9, 13, 14 and 15 of the mouse survive normally. On the other hand, only the maternal X chromosome is active in mouse extraembryonic membranes, maternal disomy 6 is lethal, while non-complementation of maternal duplication/paternal deficiency or its reciprocal for regions of chromosome 2, 8 and 17 has been recognized. We report that animals with maternal duplication/paternal deficiency and its reciprocal for each of two particular chromosome regions show anomalous phenotypes which depart from normal in opposite directions, suggesting a differential functioning of gene loci within these regions. A further example of non-complementation lethality is also reported.     

Two types of sex determination in a nematode

Sex in the nematode Caenorhabditis elegans is normally determined by a genic balance mechanism, the ratio of X chromosomes to autosomes, so that XX animals are self-fertilizing hermaphrodites and X0 animals are males. However, recessive mutations of the autosomal gene tra-1 III cause both XX and X0 animals to develop into males, and a linked dominant mutation causes both XX and X0 animals to develop into females. Here I show that these two kinds of mutation are allelic, and that stable mutant strains can be constructed in which sex is determined not by X-chromosome dosage but by the presence or absence of a single active gene. In these strains the autosomes carrying the tra-1 locus are in effect homomorphic Z and W sex chromosomes, and the sexes are homogametic ZZ males and heterogametic ZW females, in contrast to the wild-type arrangement of homogametic XX hermaphrodites and heterogametic X0 males.     

贵州2种负蝗核型和C—带的比较研究

研究了短额负蝗AtractomorphasinensisI .Bol.和云南负蝗AtractomorphayunnanensisBietXia的核型和C—带。结果表明 :2种负蝗的染色体数目均为 2n(♂ ) =18+XO =19,全部为端部着丝粒染色体 :核型公式 2n(♂ ) =2X =19t ,NF =19,都属“4B”核型 ,按相对长度 ,它们的染色体都可分成L ,M 2组 ,都具有着丝粒C带。云南负蝗后期Ⅰ染色体组绝对长度总和 (4 9 91± 0 37μm)比短额负蝗的 (4 2 5 0± 0 34 μm)长 ;但结构异染色质总量 (2 8 38± 0 2 2 % )却比短额负蝗的 (38 96± 0 16 % )少。     

In situ nick-translation distinguishes between active and inactive X chromosomes

Template-active regions of chromatin are structurally distinct from nontranscribing segments of the genome. Recently, it was suggested that the conformation of active genes which renders them sensitive to DNase I may be maintained even in fixed mitotic chromosomes. We have developed a technique of mitotic cell fixation and DNase I-directed nick-translation which distinguishes between active and inactive X chromosomes. We report here that Gerbillus gerbillus (rodent) female cells contain easily identified composite X chromosomes each of which includes the original X chromosome flanked by two characteristic autosomal segments. After nick-translation the active X chromosome in each cell is labelled specifically in both the autosomal and X-chromosomal regions. The inactive X chromosome is labelled only in the autosomal regions and in a small early replicating band within the late replicating 'original X' chromosome. Our technique opens the possibility of following the kinetics of X-chromosome inactivation and reactivation during embryogenesis, studying active genes in the inactive X chromosome and mapping tissue-specific gene clusters.     

Localization of the human GM-CSF receptor gene to the X-Y pseudoautosomal region

Mammalian sex chromosomes share a small terminal region of homologous DNA sequences, which pair and recombine during male meiosis. Alleles in this region can be exchanged between X and Y chromosomes and are therefore inherited as if autosomal. Genes from this so-called pseudoautosomal region (PAR) are present in two doses in both males and females, and escape inactivation of the X chromosome in females. Indirect evidence suggests that there must be several pseudoautosomal genes, and several candidates have been proposed. Until now, the only gene that has been unequivocally located in the PAR is MIC2, which encodes a cell-surface antigen of unknown function. We now report the localization of a gene of known function to this region--the gene for the receptor of the haemopoietic regulator, granulocyte-macrophage colony stimulating factor. The chromosomal localization of this gene may be important in understanding the generation of M2 acute myeloid leukaemia.     

Additional deletion in sex-determining region of human Y chromosome resolves paradox of X,t(Y;22) female

Whether a human embryo develops as a male or a female is determined by the presence of the Y chromosome. The sex-determining function lies entirely in interval 1A, inasmuch as most XX individuals with descended testes and normal male external genitalia carry this small region of the Y chromosome. We have localized an essential part of the sex-determining function to a portion of interval 1A, on the basis of the discovery of a female with a reciprocal Y;22 translocation and part of 1A deleted at the translocation breakpoint. Recently, a paradox has arisen with the report of four partially masculinized XX individuals who carry only a portion of interval 1A--a portion that does not overlap the deletion in the X,t(Y;22) female. These recent findings imply that the sex-determining function lies in the portion of 1A present in the four XX intersexes and not in the portion deleted in the X,t(Y;22) female. To explain the X,t(Y;22) individual, it was proposed that she was female because of a chromosomal position effect or delayed development of the gonadal soma. Here we report that the X,t(Y;22) female has a deletion of a second portion of interval 1A--a portion corresponding closely to that present in the XX intersexes. This resolves the apparent contradiction. Nonetheless, phenotype-genotype correlations suggest that two or more genetic elements in interval 1A may contribute to the sex-determining function of the Y chromosome. The X,t(Y;22) female lacks the ZFY gene but does not exhibit the complex phenotype known as Turner's syndrome, arguing against the hypothesis that ZFY is the Turner's syndrome gene on the Y chromosome.     

Evidence from mosaic analysis of the masculinizing gene her-1 for cell interactions in C. elegans sex determination.

Sex in Caenorhabditis elegans is determined by a regulatory cascade of seven interacting autosomal genes controlled by three X-linked genes in response to the X chromosome-to-autosome (X/A) ratio. XX animals (high X/A) develop as self-fertile hermaphrodites, and XO animals (low X/A) develop as males. The activity of the first gene in the sex-determining cascade, her-1, is required for male sexual development. XO her-1 loss-of-function mutants develop as self-fertile hermaphrodites, whereas XX her-1 gain-of-function mutants develop as masculinized intersexes. By genetic mosaic analysis using a fused free duplication linking her-1 to a cell-autonomous marker gene, we show here that her-1 expression in a sexually dimorphic cell is neither necessary nor sufficient for that cell to adopt a male fate. Our results suggest that her-1 is expressed in many, possibly all, cells and that its gene product can function non-autonomously through cell interactions to determine male sexual development.     

Conservation of position and exclusive expression of mouse Xist from the inactive X chromosome

X-chromosome inactivation in mammals is a regulatory phenomenon whereby one of the two X chromosomes in female cells is genetically inactivated, resulting in dosage compensation for X-linked genes between males and females. In both man and mouse, X-chromosome inactivation is thought to proceed from a single cis-acting switch region or inactivation centre (XIC/Xic). In the human, XIC has been mapped to band Xq13 (ref. 6) and in the mouse to band XD (ref. 7), and comparative mapping has shown that the XIC regions in the two species are syntenic. The recently described human XIST gene maps to the XIC region and seems to be expressed only from the inactive X chromosome. We report here that the mouse Xist gene maps to the Xic region of the mouse X chromosome and, using an interspecific Mus spretus/Mus musculus domesticus F1 hybrid mouse carrying the T(X;16)16H translocation, show that Xist is exclusively expressed from the inactive X chromosome. Conservation between man and mouse of chromosomal position and unique expression exclusively from the inactive X chromosome lends support to the hypothesis that XIST and its mouse homologue are involved in X-chromosome inactivation.