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genomic DNA

About: genomic DNA is a research topic. Over the lifetime, 15046 publications have been published within this topic receiving 663636 citations. The topic is also known as: genomic deoxyribonucleic acid & gDNA.


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Journal ArticleDOI
TL;DR: It is suggested that DNA methylation signatures distinguish brain regions and may help account for region-specific functional specialization in neurological disorders such as Rett syndrome.
Abstract: DNA methylation is a heritable modification of genomic DNA central to development, imprinting, transcriptional regulation, chromatin structure, and overall genomic stability. Aberrant DNA methylation of individual genes is a hallmark of cancer and has been shown to play an important role in neurological disorders such as Rett syndrome. Here, we asked whether normal DNA methylation might distinguish individual brain regions. We determined the quantitative DNA methylation levels of 1,505 CpG sites representing 807 genes with diverse functions, including proliferation and differentiation, previously shown to be implicated in human cancer. We initially analyzed 76 brain samples representing cerebral cortex ( n =35), cerebellum ( n =34), and pons ( n =7), along with liver samples ( n =3) from 43 individuals. Unsupervised hierarchical analysis showed clustering of 33 of 35 cerebra distinct from the clustering of 33 of 34 cerebella, 7 of 7 pons, and all 3 livers. By use of comparative marker selection and permutation testing, 156 loci representing 118 genes showed statistically significant differences—a ⩾17% absolute change in DNA methylation ( P

272 citations

Journal ArticleDOI
TL;DR: The reasons that might justify the need for so many DNA polymerases are explored, their function and mode of regulation are described, and links between mutations in DNA polymerase and human disease are considered.
Abstract: The human genome encodes at least 14 DNA-dependent DNA polymerases--a surprisingly large number. These include the more abundant, high-fidelity enzymes that replicate the bulk of genomic DNA, together with eight or more specialized DNA polymerases that have been discovered in the past decade. Although the roles of the newly recognized polymerases are still being defined, one of their crucial functions is to allow synthesis past DNA damage that blocks replication-fork progression. We explore the reasons that might justify the need for so many DNA polymerases, describe their function and mode of regulation, and finally consider links between mutations in DNA polymerases and human disease.

271 citations

Journal ArticleDOI
25 Nov 1999-Virology
TL;DR: This work affirms the existence of a conserved complement of poxvirus-specific core genes and expands the growing repertoire of virus genes that confer the unique capacity of each poxVirus family member to counter the immune responses of the infected host.

271 citations

Journal ArticleDOI
19 Sep 1980-Science
TL;DR: The sequence of a human leukocyte-derived complementary DNA, Hif-2h, which directs the formation in Escherichia coli of a polypeptide, IFN-alpha 1, with interferon (IFN) activity has been described, revealing the presence of at least eightIFN-related genes.
Abstract: The sequence of a human leukocyte-derived complementary DNA (cDNA), Hif-2h, which directs the formation in Escherichia coli of a polypeptide, IFN-alpha 1, with interferon (IFN) activity has been described. A second IFN cDNA, Hif-SN206, which also elicits synthesis of a biologically active IFN, IFN-alpha 2, is described in this article. Whereas IFN-alpha 2 is twice as active on human as on bovine cells, IFN-alpha 1 is 10 to 20 times more active on bovine than on human cells. As deduced from the cDNA's, the messenger RNA's for the two IFN's differ in length and in 20 percent of the nucleotides; the mature IFN polypeptides differ in 17 percent of the amino acids. Both IFN-alpha 1 and IFN-alpha 2 differ from the lymphoblastoid IFN described by others. Therefore, at least three different IFN-alpha genes are expressed in man; studies on genomic DNA reveal the presence of at least eight IFN-related genes.

270 citations

Journal ArticleDOI
TL;DR: It is determined that the L1 reverse transcriptase can faithfully replicate its own transcript and has a base misincorporation error rate of ∼1/7,000 bases, indicating that L1 retrotransposition in transformed human cells can lead to a variety of genomic rearrangements and suggest that host processes act to restrict L1 integration in cultured human cells.
Abstract: Long interspersed element 1 (LINE-1 or L1) is an abundant retrotransposon that comprises ∼17% of human DNA (43, 69). Most L1s are retrotransposition defective because they are 5′ truncated, contain internal rearrangements, or harbor mutations within their open reading frames (25, 43). However, the average human genome is estimated to contain ∼80 to 100 retrotransposition-competent L1s (RC-L1s), and approximately 10% of these elements are classified as highly active or “hot” (6, 63). Human RC-L1s are ∼6.0 kb and contain a 5′ untranslated region (UTR), two nonoverlapping open reading frames (ORF1 and ORF2), and a 3′ UTR that ends in a poly(A) tail (Fig. ​(Fig.1A)1A) (13, 53, 66). ORF1 encodes a 40-kDa nucleic acid binding protein (30, 31, 33), whereas ORF2 has the potential to encode a 150-kDa protein with demonstrated endonuclease (L1 EN) and reverse transcriptase (L1 RT) activities (15, 19, 22, 51). ORF2p also contains a cysteine-rich domain (CX3CX7HX4C) of unknown function (17, 54). Both proteins are required for retrotransposition in cis (54), which most probably occurs by a mechanism termed “target site primed reverse transcription” (TPRT) (19, 47, 54, 72). However, how L1 integration is completed remains a mystery. FIG. 1. Simple sequence alterations at the 5′ genomic DNA/L1 junction. A. Rationale of the assay. The 3′ UTR of a human RC-L1 was tagged with a reporter cassette designed to detect retrotransposition events. Open rectangles indicate L1 ORF1 and ... We recently developed a plasmid-based rescue system that allows the recovery of L1 insertions in cultured human HeLa cells with minimal influence from selective pressures that occur during genome evolution. We found that L1 retrotransposition is associated with various forms of genetic instability and that the nascent L1 cDNA can undergo recombination with endogenous L1 elements, resulting in the formation of chimeric L1s. Consistent findings by Symer et al., using a colon cell line (HCT116) with an essentially normal karyotype, have led to the hypothesis that L1 retrotransposition can lead to various types of genomic instability (21, 72). Here, we describe the analysis of 100 L1 retrotransposition events in HeLa cells derived from four previously characterized RC-L1s (L1.2A, LRE-2, L1.3, and L1RP). Consistent with previous studies, we have found that retrotransposition is associated with the generation of intrachromosomal deletions, the creation of chimeric L1 elements, and the addition of non-L1 nucleotides at the 5′ insertion junction (21, 56, 72). In addition, we have observed novel rearrangements, including the mobilization of U6 small uracil-rich nuclear RNA (U6 snRNA) to a new genomic location, the formation of intrachromosomal duplications, intra-L1 rearrangements, and the generation of a possible interchromosomal translocation. Finally, we have determined that the L1 RT can faithfully replicate its own transcript and has a base misincorporation error rate of ∼1/7,000 bases. Together, these data indicate that the resolution of L1 retrotransposition intermediates in transformed human cell lines can lead to a variety of genomic rearrangements and lead us to propose that host processes act to restrict L1 retrotransposition during integration, limiting the number of full-length L1s in the genome.

270 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
2023258
2022431
2021232
2020261
2019273
2018339