Cloning of breakpoints of a chromosome translocation identifies the AN2 locus

Chromosome translocations involving 11p13 have been associated with familial aniridia in two kindreds highlighting the chromosomal localization of the AN2 locus. This locus is also part of the WAGR complex (Wilms tumor, aniridia, genitourinary abnormalities, and mental retardation). In one kindred, the translocation is associated with a deletion, and probes for this region were used to identify and clone the breakpoints of the translocation in the second kindred. Comparison of phage restriction maps exclude the presence of any sizable deletion in this case. Sequences at the chromosome 11 breakpoint are conserved in multiple species, suggesting that the translocation falls within the AN2 gene.     

Two anonymous DNA segments distinguish the Wilms' tumor and aniridia loci

The association of Wilms' tumor with aniridia (the WAGR complex) in children with 11p13 chromosomal abnormalities has been established, but the paucity of molecular probes in 11p13 has hampered identification of the responsible genes. Two new anonymous DNA segments have been identified that map to the WAGR region of 11p13. Both DNA probes identify a cytologically undetectable deletion associated with a balanced chromosome translocation inherited by a patient with familial aniridia, but not Wilms' tumor. The same two DNA segments are also included in the distal p13-p14.1 deletion of another patient, who has aniridia, Wilms' tumor, and hypogonadism, but they are not included in the p12-p13 deletion of a third patient, who does not have aniridia but has had a Wilms' tumor. The discovery of this aniridia deletion and these two DNA segments that physically separate the Wilms' tumor and aniridia loci should facilitate identification of the genes in the WAGR locus, beginning with the aniridia gene.     

Chromosomal localization of muscle nicotinic acetylcholine receptor genes in the mouse

The chromosomal localization of the genes encoding the four subunits of muscle nicotinic receptor was determined by analyzing restriction fragment length polymorphisms between two mouse species Mus musculus domesticus (DBA/2) and Mus spretus (SPE). Analysis of the progeny of the interspecies mouse backcross (DBA/2 X SPE) X DBA/2 showed that the alpha-subunit gene cosegregates with the alpha-cardiac actin gene on chromosome 17, that the beta-subunit gene is located on chromosome 11, and that the gamma- and delta-subunit genes cosegregate and are located on chromosome 1.     

Computer-assisted analysis of chromosomal abnormalities: detection of a deletion in aniridia-Wilms' tumor syndrome

A chromosome translocation, t(8p + ; 11q -), in a patient with aniridia and Wilms' tumor, appeared balanced by standard techniques, including trypsin banding. Computer analysis of optical microscope scanning profiles of chromosome pairs 8 and 11 revealed an interstitial deletion of the short arm of 8. Computer analysis coupled to the new banding techniques provides greater resolution for the detection of subtle chromosomal variations not recognized by banding methods alone.     

Mouse models of tumor development in neurofibromatosis type 1

Neurofibromatosis type 1 (NF1) is a prevalent familial cancer syndrome resulting from germ line mutations in the NF1 tumor suppressor gene. Hallmark features of the disease are the development of benign peripheral nerve sheath tumors (neurofibromas), which can progress to malignancy. Unlike humans, mice that are heterozygous for a mutation in Nf1 do not develop neurofibromas. However, as described here, chimeric mice composed in part of Nf1-/- cells do, which demonstrates that loss of the wild-type Nf1 allele is rate-limiting in tumor formation. In addition, mice that carry linked germ line mutations in Nf1 and p53 develop malignant peripheral nerve sheath tumors (MPNSTs), which supports a cooperative and causal role for p53 mutations in MPNST development. These two mouse models provide the means to address fundamental aspects of disease development and to test therapeutic strategies.     

An X chromosome gene, WTX, is commonly inactivated in Wilms tumor

Wilms tumor is a pediatric kidney cancer associated with inactivation of the WT1 tumor-suppressor gene in 5 to 10% of cases. Using a high-resolution screen for DNA copy-number alterations in Wilms tumor, we identified somatic deletions targeting a previously uncharacterized gene on the X chromosome. This gene, which we call WTX, is inactivated in approximately one-third of Wilms tumors (15 of 51 tumors). Tumors with mutations in WTX lack WT1 mutations, and both genes share a restricted temporal and spatial expression pattern in normal renal precursors. In contrast to biallelic inactivation of autosomal tumor-suppressor genes, WTX is inactivated by a monoallelic "single-hit" event targeting the single X chromosome in tumors from males and the active X chromosome in tumors from females.     

小鼠卵子突变基因功能表达的研究

近交系小鼠DDK具有一种奇异的繁殖特性(DDK综合症).这种特性是由于DDK卵子细胞质物质和其它品系精子因子之间存在的一种不亲合性引起的,它们二者均受到位于小鼠第11条染色体的卵子突变(OvumMutant或Om)位点上的1对等位基因所控制.本文介绍的研究成果包括:1)发现了存在于C57BL/6(B6)品系小鼠遗传背景中新的修饰基因,其使得杂合型(Om/ )雌鼠的胚胎死亡率增加,并提出了运用“等位基因排斥”理论解释修饰基因作用机理的假说;2)论证了DDK品系本身遗传背景中不具有使杂合型(Om/ )雌鼠胚胎死亡率降低的修饰基因;3)证明了小鼠遗传背景中,不存在通过杂合型(Om/ )雄鼠的精子影响DDK(Om/Om)雌鼠胚胎死亡率高低的修饰基因;4)通过不同亚种间近交系小鼠的杂交发现,在欧洲起源的DDK品系(Mus musculus domesticus)和日本起源的MOM品系(M.m.molossinus),以及和菲律宾起源的CASP品系(M.m.castaneus)之间,不存在卵子细胞质物质和精子的不亲合性,但CASP品系的卵子细胞质物质与B6品系的精子间可能存在着不亲合性.     

Duplication, deletion, and polymorphism in the sex-determining region of the mouse Y chromosome

The ZFY gene in the sex-determining region of the human Y chromosome encodes a "zinc-finger" protein that may be the testis-determining factor, TDF. Although the Y chromosomes of most placental mammals carry a single homolog of ZFY, the mouse Y chromosome has two homologs, both in the sex-determining (Sxr) region. Zfy-1 alone may suffice to determine maleness; Zfy-2 is dispensable, as it was deleted in an Sxr variant that retains sex-determining function but has lost other genes. Both loci mapped near the centromere of the mouse Y chromosome. The Y chromosomes of the subspecies Mus musculus musculus and M. m. domesticus were distinguishable by a Zfy-1 restriction fragment polymorphism, which can be used to study their differing interactions with autosomal sex-determining genes.     

Cloning RPL11 cDNA 3'' End by SMART RACE Technique

RT-PCR and RACE techniques were used to clone 3' end real sequence of RPL11 gene from a goat. The sequences included some non-structural protein (3D) genes, and 3D gene immediately downstream 3' non-coding region (UTR) and poly (A) tail. The results showed that the length of specific amplified fragment was 566 bp (not including polyA tail). RPL11 gene encoded 188 amino acids, amino acid sequence was conducted for homology analysis by NCBI BLAST tool. The highest homology was Mus (RPL11, mRNA homology 99%), ...     

Transfection of v-rasH DNA into MCF-7 human breast cancer cells bypasses dependence on estrogen for tumorigenicity

The natural history of estrogen-responsive breast cancers often involves a phenotypic change to an estrogen-unresponsive, more aggressive tumor. The human breast cancer cell line, MCF-7, which requires estradiol for tumor formation in vivo and shows growth stimulation in response to estradiol in vitro, is a model for hormone-responsive tumors. The v-rasH onc gene was transfected into MCF-7 cells. The cloned MCF-7ras transfectants, which expressed the v-rasH messenger RNA and v-rasH p21 protein (21,000 daltons), were characterized. In contrast to the parental cell line, MCF-7ras cells no longer responded to exogenous estrogen in culture and their growth was minimally inhibited by exogenous antiestrogens. When tested in the nude mouse, the MCF-7ras cells were fully tumorigenic in the absence of estrogen supplementation. Thus, cells acquiring an activated onc gene can bypass the hormonal regulatory signals that trigger the neoplastic growth of a human breast cancer cell line.     

Human chromosome 12 is required for elevated HIV-1 expression in human-hamster hybrid cells

Host cell factors act together with regulatory genes of the human immunodeficiency virus (HIV) to control virus production. Human-Chinese hamster ovary hybrid cell clones were used to probe for human chromosomes involved in regulating HIV gene expression. DNA transfection experiments showed that 4 of 18 clones had high levels of HIV gene expression measured by both extracellular virus production and transactivation of the HIV long terminal repeat in the presence of the trans-activator (tat) gene. Karyotype analyses revealed a 94% concordance (17/18) between human chromosome 12 and HIV gene expression. Other chromosomes had an 11 to 72% concordance with virus production.     

3个新引进黑杨无性系间水分利用效率差异性研究

北美杂交黑杨是一种速生但高耗水的树种,筛选高水分利用效率的黑杨品系有重要的理论和实际意义.本文研究了不同水分处理下,3个不同黑杨无性系DN-2、R-270、NE-19的长期水分利用效率(WUE<,L>)、瞬时水分利用效率(WUE<,i>)、叶片碳同位素组成(δ<'13>C)、光合速率(P<,n>)、气孔行为及其相互关系...     

Assignment of the gene for myelin proteolipid protein to the X chromosome: implications for X-linked myelin disorders

Several inherited disorders in humans and in rodents result in myelin dysgenesis and a deficiency of the molecular constituents of myelin. A complementary DNA to one of the two major myelin proteins, myelin proteolipid protein (also known as lipophilin), has been used with Southern blot analysis of somatic cell hybrid DNA to map the human proteolipid protein gene to the middle of the long arm of the human X chromosome (bands Xq13-Xq22) and to assign the murine proteolipid protein gene to the mouse X chromosome. Comparison of the gene maps of the human and mouse X chromosomes suggests that myelin proteolipid protein may be involved in X-linked mutations at the mouse jimpy locus and has implications for Pelizaeus-Merzbacher disease, a human inherited X-linked myelin disorder.     

Deletion in chromosome 11p associated with a hepatitis B integration site in hepatocellular carcinoma

Hepatitis B virus (HBV), a virus with known carcinogenic potential, integrates into cellular DNA during long-term persistent infection in man. Hepatocellular carcinomas isolated from viral carriers often contain clonally propagated viral DNA integrations. As small chromosomal deletions are associated with several types of carcinomas, the occurrence of chromosomal deletions in association with HBV integration in hepatocellular carcinoma was studied. HBV integration was accompanied by a deletion of at least 13.5 kilobases of cellular sequences in a human hepatocellular carcinoma. The viral DNA integration and deletion of cellular sequences occurred on the short arm of chromosome 11 at location 11p13-11p14. The cellular sequences that were deleted at the site of HBV integration were lost from the tumor cells, leaving only a single copy of the remaining cellular allele.     

Involvement of mammalian Mus81 in genome integrity and tumor suppression

Mus81-Eme1 endonuclease has been implicated in the rescue of stalled replication forks and the resolution of meiotic recombination intermediates in yeast. We used gene targeting to study the physiological requirements of Mus81 in mammals. Mus81-/- mice are viable and fertile, which indicates that mammalian Mus81 is not essential for recombination processes associated with meiosis. Mus81-deficient mice and cells were hypersensitive to the DNA cross-linking agent mitomycin C but not to gamma-irradiation. Remarkably, both homozygous Mus81-/- and heterozygous Mus81+/- mice exhibited a similar susceptibility to spontaneous chromosomal damage and a profound and equivalent predisposition to lymphomas and other cancers. These studies demonstrate a critical role for the proper biallelic expression of the mammalian Mus81 in the maintenance of genomic integrity and tumor suppression.