Complex reorganization and predominant non-homologous repair following chromosomal breakage in karyotypically balanced germline rearrangements and transgenic integration

We defined the genetic landscape of balanced chromosomal rearrangements at nucleotide resolution by sequencing 141 breakpoints from cytogenetically interpreted translocations and inversions. We confirm that the recently described phenomenon of 'chromothripsis' (massive chromosomal shattering and reorganization) is not unique to cancer cells but also occurs in the germline, where it can resolve to a relatively balanced state with frequent inversions. We detected a high incidence of complex rearrangements (19.2%) and substantially less reliance on microhomology (31%) than previously observed in benign copy-number variants (CNVs). We compared these results to experimentally generated DNA breakage-repair by sequencing seven transgenic animals, revealing extensive rearrangement of the transgene and host genome with similar complexity to human germline alterations. Inversion was the most common rearrangement, suggesting that a combined mechanism involving template switching and non-homologous repair mediates the formation of balanced complex rearrangements that are viable, stably replicated and transmitted unaltered to subsequent generations.     

贵州省遵义地区表层土壤中多环芳烃分布特征

调查研究了151个取至贵州省遵义地区12个市(县)的土壤中的多环芳烃(PAHs)的背景含量及与各市(县)总污染物排放量的关系.遵义地区各县(市)表层土壤中PAHs含量介于0.8～251 μg/kg,从单个化合物的检出情况来看,主要以二环、三环和四环PAHs检出率较高,其中四环以苯并(a)蒽,苯并(b)蒽及屈为主,检出率分别为41.7%,38.1%和34.4%.三环PAHs中以菲与蒽的检出率较高分别为37.1%和30.5%,具有两个环化合物以芴与苊为主,检出率分别为41.1%和27.8%.遵义地区各县(市)表层土壤PAHs检出特征虽大体相同,但其含量却有较大差异,其中遵义县∑PAHs的含量最最高,平均为74.5μg/kg,最低为绥阳县为13.74μg/kg,各采样点平均16种PAHs含量从低到高依次为:绥阳县、湄潭县、桐梓县、仁怀、务川县、余庆县、凤冈县、正安县、习水县、赤水县、道真县和遵义县.各县∑PAHs含量的差异与该县市空气与废水排放总量呈显著正相关,相关系数r为0.971,表明贵州土壤中的PAHs主要来自于能源物质的燃烧和PAHs全球范围内的自然迁移,但土壤处于较低污染状态.     

免疫胶体金对小鼠巨噬细胞和NK细胞活性的影响

实验设计了4种直径和3种剂量12个组合的胶体金对小白鼠进行注射处理：采用MTT法和LDH短程释放法．测定了腹腔巨嗜细胞活性和脾脏NK细胞活性．结果表明：不同直径和剂量的CG对机体有不同程度的影响。其中直径15nm．10nmCG的0．3mL和0．2mL剂量组可显著提高腹腔巨噬细胞活性及脾脏NK细胞杀伤活性,0．1mL剂量组虽有提高但不显著;直径5nm．20nm各个剂量组效果的波动较大,中、高剂量组对四项指标起促进作用但不显著．低剂量组则没有促进作用。证明了15nm和10nm中高剂量的胶体金可显著提高小鼠巨噬细胞功能和脾脏NK细胞活性。     

二维灰度直方图上的距离判别分割方法

在图像的二维灰度直方图上,通过距离判别的方法得出在其上进行聚类划分的依据,即一条二次曲线．用此曲线进行分割的优点在于能考虑到二维灰度直方图上的所有像素点．理论分析和实验结果都表明,此方法较二维灰度直方图上的其它阈值分割方法优越．     

The Shwachman-Bodian-Diamond syndrome protein mediates translational activation of ribosomes in yeast

The autosomal recessive disorder Shwachman-Diamond syndrome, characterized by bone marrow failure and leukemia predisposition, is caused by deficiency of the highly conserved Shwachman-Bodian-Diamond syndrome (SBDS) protein. Here, we identify the function of the yeast SBDS ortholog Sdo1, showing that it is critical for the release and recycling of the nucleolar shuttling factor Tif6 from pre-60S ribosomes, a key step in 60S maturation and translational activation of ribosomes. Using genome-wide synthetic genetic array mapping, we identified multiple TIF6 gain-of-function alleles that suppressed the pre-60S nuclear export defects and cytoplasmic mislocalization of Tif6 observed in sdo1Delta cells. Sdo1 appears to function within a pathway containing elongation factor-like 1, and together they control translational activation of ribosomes. Thus, our data link defective late 60S ribosomal subunit maturation to an inherited bone marrow failure syndrome associated with leukemia predisposition.     

Mutations in the gene encoding the basal body protein RPGRIP1L, a nephrocystin-4 interactor, cause Joubert syndrome

Protein-protein interaction analyses have uncovered a ciliary and basal body protein network that, when disrupted, can result in nephronophthisis (NPHP), Leber congenital amaurosis, Senior-L?ken syndrome (SLSN) or Joubert syndrome (JBTS). However, details of the molecular mechanisms underlying these disorders remain poorly understood. RPGRIP1-like protein (RPGRIP1L) is a homolog of RPGRIP1 (RPGR-interacting protein 1), a ciliary protein defective in Leber congenital amaurosis. We show that RPGRIP1L interacts with nephrocystin-4 and that mutations in the gene encoding nephrocystin-4 (NPHP4) that are known to cause SLSN disrupt this interaction. RPGRIP1L is ubiquitously expressed, and its protein product localizes to basal bodies. Therefore, we analyzed RPGRIP1L as a candidate gene for JBTS and identified loss-of-function mutations in three families with typical JBTS, including the characteristic mid-hindbrain malformation. This work identifies RPGRIP1L as a gene responsible for JBTS and establishes a central role for cilia and basal bodies in the pathophysiology of this disorder.     

A genome-wide association study for celiac disease identifies risk variants in the region harboring IL2 and IL21

We tested 310,605 SNPs for association in 778 individuals with celiac disease and 1,422 controls. Outside the HLA region, the most significant finding (rs13119723; P = 2.0 x 10(-7)) was in the KIAA1109-TENR-IL2-IL21 linkage disequilibrium block. We independently confirmed association in two further collections (strongest association at rs6822844, 24 kb 5' of IL21; meta-analysis P = 1.3 x 10(-14), odds ratio = 0.63), suggesting that genetic variation in this region predisposes to celiac disease.