Retrotransposition and Structural Variation in the Human Genome

Department of Molecular and Human Genetics, Baylor College of Medicine and Texas Children's Hospital, Houston, TX 77030, USA.
Cell (Impact Factor: 32.24). 06/2010; 141(7):1110-2. DOI: 10.1016/j.cell.2010.06.014
Source: PubMed


New assays are revealing that the diploid human genome contains extensive amounts of structural variation. Genome-wide approaches described in three papers in this issue (Beck et al., 2010; Huang et al., 2010; Iskow et al., 2010) paint a dynamic portrait of our genome, revealing a prominent role for repetitive sequences in shaping its structural variation.

Full-text preview

Available from:
  • Source
    • "Rodić and Burns 2013), and, also, on genome evolution (e.g. Martin et al. 2005; Wallace et al. 2008; Lee et al. 2010; Lupski 2010; Martin 2010). LINE-1 retrotransposition can cause shuffling of gene promoters, enhancers and even exons, by the transcription of flanking non-LINE-1 sequences (e.g. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Long interspersed nuclear elements-1 (LINE-1) are the most abundant and active retrotransposons in the mammalian genomes. Traditionally, the occurrence of LINE-1 sequences in the genome of mammals has been explained by the selfish DNA hypothesis. Nevertheless, recently, it has also been argued that these sequences could play important roles in these genomes, as in the regulation of gene expression, genome modelling and X-chromosome inactivation. The non-random chromosomal distribution is a striking feature of these retroelements that somehow reflects its functionality. In the present study, we have isolated and analysed a fraction of the open reading frame 2 (ORF2) LINE-1 sequence from three rodent species, Cricetus cricetus, Peromyscus eremicus and Praomys tullbergi. Physical mapping of the isolated sequences revealed an interspersed longitudinal AT pattern of distribution along all the chromosomes of the complement in the three genomes. A detailed analysis shows that these sequences are preferentially located in the euchromatic regions, although some signals could be detected in the heterochromatin. In addition, a coincidence between the location of imprinted gene regions (as Xist and Tsix gene regions) and the LINE-1 retroelements was also observed. According to these results, we propose an involvement of LINE-1 sequences in different genomic events as gene imprinting, X-chromosome inactivation and evolution of repetitive sequences located at the heterochromatic regions (e.g. satellite DNA sequences) of the rodents' genomes analysed.
    Full-text · Article · Aug 2014 · Journal of applied genetics
  • Source
    • "These effects contribute to phenotypic variations or increase disease risks23242526. Microarray technology is widely used in toxicological studies of CNVs172425262728. However, information of CNVs in benzene-exposed workers is limited. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Long-term exposure to benzene causes several adverse health effects, including an increased risk of acute myeloid leukemia. This study was to identify genetic alternations involved in pathogenesis of leukemia in benzene-exposed workers without clinical symptoms of leukemia. This study included 33 shoe-factory workers exposed to benzene at levels from 1 ppm to 10 ppm. These workers were divided into 3 groups based on the benzene exposure time, 1- < 7, 7- < 12, and 12- < 24 years. 17 individuals without benzene exposure history were recruited as controls. Cytogenetic analysis using Affymetrix Cytogenetics Array found copy-number variations (CNVs) in several chromosomes of benzene-exposed workers. Expression of targeted genes in these altered chromosomes, NOTCH1 and BSG, which play roles in leukemia pathogenesis, was further examined using real-time PCR. The NOTCH1 mRNA level was significantly increased in all 3 groups of workers, and the NOTCH1 mRNA level in the 12- < 24 years group was significantly higher than that in 1- < 7 and 7- < 12 years groups. Compared to the controls, the BSG mRNA level was significantly increased in 7- < 12 and 12- < 24 years groups, but not in the 1- < 7 years group. These results suggest that CNVs and leukemia-related gene expression might play roles in leukemia development in benzene-exposed workers.
    Full-text · Article · Jul 2014 · Scientific Reports
  • Source
    • "However, TEs do not transpose randomly within the genome: LINEs tend to re-insert into GC-poor regions, and Alus (and HERVs) into GC-rich regions [Pavlicek et al., 2001]. Together these findings provide a highly dynamic portrait of the genome where individuals differ not only with respect to presence or absence of various L1 insertions, but also to the relative position of the insertion [Lupski, 2010]. Fig. 3. Effects of TEs on human genome expression. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Transposable Elements (TEs) or transposons are low-complexity elements (e.g., LINEs, SINEs, SVAs, and HERVs) that make up to two-thirds of the human genome. There is mounting evidence that TEs play an essential role in genomic architecture and regulation related to both normal function and disease states. Recently, the identification of active TEs in several different human brain regions suggests that TEs play a role in normal brain development and adult physiology and quite possibly in psychiatric disorders. TEs have been implicated in hemophilia, neurofibromatosis, and cancer. With the advent of next-generation whole-genome sequencing approaches, our understanding of the relationship between TEs and psychiatric disorders will greatly improve. We will review the biology of TEs and early evidence for TE involvement in psychiatric disorders. © 2014 Wiley Periodicals, Inc.
    Full-text · Article · Apr 2014 · American Journal of Medical Genetics Part B Neuropsychiatric Genetics
Show more