Abstract:
:Transposable elements (TEs) are major sources of new exons in higher eukaryotes. Almost half of the human genome is derived from TEs, and many types of TEs have the potential to exonize. In this work, we conducted a large-scale analysis of human exons derived from mammalian-wide interspersed repeats (MIRs), a class of old TEs which was active prior to the radiation of placental mammals. Using exon array data of 328 MIR-derived exons and RT-PCR analysis of 39 exons in 10 tissues, we identified 15 constitutively spliced MIR exons, and 15 MIR exons with tissue-specific shift in splicing patterns. Analysis of RNAs from multiple species suggests that the splicing events of many strongly included MIR exons have been established before the divergence of primates and rodents, while a small percentage result from recent exonization during primate evolution. Interestingly, exon array data suggest substantially higher splicing activities of MIR exons when compared with exons derived from Alu elements, a class of primate-specific retrotransposons. This appears to be a universal difference between exons derived from young and old TEs, as it is also observed when comparing Alu exons to exons derived from LINE1 and LINE2, two other groups of old TEs. Together, this study significantly expands current knowledge about exonization of TEs. Our data imply that with sufficient evolutionary time, numerous new exons could evolve beyond the evolutionary intermediate state and contribute functional novelties to modern mammalian genomes.
journal_name
Hum Mol Genetjournal_title
Human molecular geneticsauthors
Lin L,Jiang P,Shen S,Sato S,Davidson BL,Xing Ydoi
10.1093/hmg/ddp152subject
Has Abstractpub_date
2009-06-15 00:00:00pages
2204-14issue
12eissn
0964-6906issn
1460-2083pii
ddp152journal_volume
18pub_type
杂志文章abstract::Sphingosine-1-phosphate (S1P) is a lipid-signaling molecule produced by sphingosine kinase in response to a wide number of stimuli. By acting through a family of widely expressed G protein-coupled receptors, S1P regulates diverse physiological processes. Here we examined the role of S1P signaling in neurodegeneration ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddn126
更新日期:2008-08-01 00:00:00
abstract::Xeroderma pigmentosum (XP) complementation group F was first reported in Japan and most XP-F patients reported to date are Japanese. The clinical features of XP-F patients are rather mild, including late onset of skin cancer. Recently a cDNA that corrects the repair deficiency of cultured XP-F cells was isolated. The ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/7.6.969
更新日期:1998-06-01 00:00:00
abstract::We have recently described the identification of a second IDS locus (IDS-2) located within 90 kb telomeric of the IDS gene (Bondeson et al. submitted). Here, we show that this region is involved in a recombination event with the IDS gene in about 13% of patients with the Hunter syndrome. Analysis of the resulting rear...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/4.4.615
更新日期:1995-04-01 00:00:00
abstract::The RIG-I-like receptors (RLRs)--RIG-I, IFIH1 (or MDA5) and LGP2--are thought to be key actors in the innate immune system, as they play a major role in sensing RNA viruses in the cytosol of host cells. Despite the increasingly recognized importance of the RLR family in antiviral immunity, no population genetic studie...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddr377
更新日期:2011-11-15 00:00:00
abstract::The MELAS syndrome is a mitochondrial encephalomyopathy associated with a point mutation at nucleotide 3243 of mitochondrial DNA (mtDNA). The same mutation has also been found in patients with maternally inherited diabetes mellitus. The mutation occurs within a sequence needed for termination of mitochondrial transcri...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/2.5.525
更新日期:1993-05-01 00:00:00
abstract::CHD7 mutations are implicated in a majority of cases of the congenital disorder, CHARGE syndrome. CHARGE, an autosomal dominant syndrome, is known to affect multiple tissues including eye, heart, ear, craniofacial nerves and skeleton and genital organs. Using a morpholino-antisense-oligonucleotide-based zebrafish mode...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddw198
更新日期:2016-08-15 00:00:00
abstract::Migraine affects ∼14% of the world's population, though not all predisposing causal risk factors are known. We used electronic health records, genetic co-heritability analysis, and a two-sample Mendelian Randomization (MR) design to determine if elevated serum calcium levels were associated with risk of migraine heada...
journal_title:Human molecular genetics
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1093/hmg/ddw416
更新日期:2017-02-15 00:00:00
abstract::CDH3/P-cadherin is a classical cadherin. Overexpression of which has been associated with proliferative lesions of high histological grade, decreased cell polarity and poor survival of patients with breast cancer. In vitro studies showed that it can be up-regulated by ICI 182,780, suggesting that the lack of ERalpha s...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddq134
更新日期:2010-07-01 00:00:00
abstract::Rothmund-Thomson syndrome (RTS) is a rare autosomal recessive disorder characterized by poikiloderma, small stature, sparse hair, skeletal abnormalities, increased risk of osteosarcoma, and decreased bone mass. To date, there has not been a comprehensive evaluation of the prevalence and extent of metabolic bone diseas...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddx178
更新日期:2017-08-15 00:00:00
abstract::We report identification of a novel genetic locus (GLC1P) for normal tension glaucoma (NTG) on chromosome 12q14 using linkage studies of an African-American pedigree (maximum non-parametric linkage score = 19.7, max LOD score = 2.7). Subsequent comparative genomic hybridization and quantitative polymerase chain reacti...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddr123
更新日期:2011-06-15 00:00:00
abstract::Pathological modifications in the microtubule-associated protein Tau is a common characteristic observed in different neurological diseases, suggesting that analogous metabolic pathways might be similarly affected during neurodegeneration. To identify these molecules and mechanisms, we utilized Drosophila models of hu...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddu393
更新日期:2014-12-20 00:00:00
abstract::Mucolipidosis IV (MLIV) is an orphan neurodevelopmental disease that causes severe neurologic dysfunction and loss of vision. Currently there is no therapy for MLIV. It is caused by loss of function of the lysosomal channel mucolipin-1, also known as TRPML1. Knockout of the Mcoln1 gene in a mouse model mirrors clinica...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddy182
更新日期:2018-08-01 00:00:00
abstract::Cataract is one of the major causes of blindness in humans. We describe here an autosomal dominant polymorphic congenital cataract (PCC) which is characterised by wide variations in phenotype of non-nuclear lens opacities, even among affected members of the same family. PCC families included a large, unique pedigree (...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/5.5.699
更新日期:1996-05-01 00:00:00
abstract::Retinoblastoma is a non-hereditary as well as an inherited pediatric tumor of the developing retina resulting from the inactivation of both copies of the RB1 tumor suppressor gene. Familial retinoblastoma is a highly penetrant genetic disease that usually develops by carrying germline mutations that inactivate one all...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddu245
更新日期:2014-10-01 00:00:00
abstract::Huntington disease (HD) is a genetic neurodegenerative disorder for which there is currently no cure and no way to stop or even slow the brain changes it causes. In the present study, we aimed to investigate whether FTY720, the first approved oral therapy for multiple sclerosis, may be effective in HD models and event...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddt615
更新日期:2014-05-01 00:00:00
abstract::α-Synuclein and mutant huntingtin are the major constituents of the intracellular aggregates that characterize the pathology of Parkinson's disease (PD) and Huntington's disease (HD), respectively. α-Synuclein is likely to be a major contributor to PD, since overexpression of this protein resulting from genetic tripli...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddr477
更新日期:2012-02-01 00:00:00
abstract::X chromosome inactivation (XCI) is an epigenetic mechanism that silences the majority of genes on one X chromosome in females. Previous studies have suggested that the spread of XCI might be facilitated in part by common repeats such as long interspersed nuclear elements (LINEs). However, owing to the unusual sequence...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddt553
更新日期:2014-03-01 00:00:00
abstract::The rapid increase in the prevalence of type 2 diabetes (T2D) represents a major challenge for health care delivery worldwide. Identification of genes influencing individual susceptibility to disease offers a route to better understanding of the molecular mechanisms underlying pathogenesis, a necessary prerequisite fo...
journal_title:Human molecular genetics
pub_type: 杂志文章,评审
doi:10.1093/hmg/ddh057
更新日期:2004-04-01 00:00:00
abstract::As the powerhouses of the eukaryotic cell, mitochondria must maintain their genomes which encode proteins essential for energy production. Mitochondria are characterized by guanine-rich DNA sequences that spontaneously form unusual three-dimensional structures known as G-quadruplexes (G4). G4 structures can be problem...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddaa043
更新日期:2020-05-28 00:00:00
abstract::The clearest example of genomic imprinting in humans comes from studies of the Angelman (AS) and Prader-Willi (PWS) syndromes. Although these are clinically distinct disorders, both typically result from a loss of the same chromosomal region, 15q11-q13. AS usually results from either a maternal deletion of this region...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/2.9.1377
更新日期:1993-09-01 00:00:00
abstract::Twist1 is a basic helix-loop-helix transcription factor, essential during early development in mammals. While Twist1 induces epithelial-to-mesenchymal transition (EMT), here we show that Twist1 overexpression enhances nuclear and mitotic aberrations. This is accompanied by an increase in whole chromosomal copy number ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddaa076
更新日期:2020-06-27 00:00:00
abstract::Supravalvular aortic stenosis (SVAS) is an inherited obstructive vascular disease that affects the aorta, carotid, coronary and pulmonary arteries. Previous molecular genetic data have led to the hypothesis that SVAS results from mutations in the elastin gene, ELN. In these studies, the disease phenotype was linked to...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/6.7.1021
更新日期:1997-07-01 00:00:00
abstract::Autosomal dominant familial spastic paraplegia (FSP) is a genetically heterogeneous neurodegenerative disorder displaying anticipation for which three loci have been mapped to the chromosomal positions 14q11.2-q24.3 (SPG3), 2p21-p24 (SPG4) and 15q11.1 (SPG6). The repeat expansion detection (RED) method has been used t...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/7.11.1779
更新日期:1998-10-01 00:00:00
abstract::Mutations of the leucine-rich glioma-inactivated 1 (LGI1) gene cause an autosomal dominant partial epilepsy with auditory features also known as autosomal-dominant lateral temporal lobe epilepsy. LGI1 is also the main antigen present in sera and cerebrospinal fluids of patients with limbic encephalitis and seizures, h...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/dds184
更新日期:2012-08-15 00:00:00
abstract::Mutations in both alleles of the tumour suppressor gene coding for merlin/schwannomin, an ERM family protein, cause the hereditary disease neurofibromatosis type 2 (NF2). NF2 is characterized by the development of multiple nervous system tumours especially vestibular schwannomas. Efficient oncoretrovirus-mediated gene...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/11.1.69
更新日期:2002-01-01 00:00:00
abstract::Gamma glutamyl cysteine ligase (GCL) is the rate-limiting enzyme for intracellular glutathione (GSH) synthesis. The GSH concentration and GCL activity are declining with age in the central nervous system (CNS), and is accompanied by elevated reactive oxygen species (ROS). To study the biological effects of low GSH lev...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddx040
更新日期:2017-04-01 00:00:00
abstract::X-linked agammaglobulinaemia (XLA) is an inherited immunodeficiency resulting from mutations in the gene for a cytoplasmic protein tyrosine kinase (Btk). We have utilised reverse-transcription-based PCR in combination with the chemical cleavage and mismatch technique (CCM) to screen for Btk mutations in 42 unrelated p...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/4.4.693
更新日期:1995-04-01 00:00:00
abstract::In the normal diploid mouse embryo, active demethylation of the paternal genome but not of the maternal genome occurs within only a few hours and in a highly coordinated fashion as the zygote proceeds through the first G1 phase. This zygotic demethylation may be necessary to reprogram the sperm genome for somatic deve...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/10.26.2983
更新日期:2001-12-15 00:00:00
abstract::Immunoglobulins play an essential part in the immune system, and immunoglobulin deficiencies can have profound medical consequences. The genetic control and regulation of the immunoglobulin response is therefore of interest. Previous investigations have identified a number of loci influencing total and specific IgE le...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/7.1.27
更新日期:1998-01-01 00:00:00
abstract::We have cloned, sequenced and annotated segments of DNA spanning the mouse, chicken and pufferfish alpha globin gene clusters and compared them with the corresponding region in man. This has defined a small segment ( approximately 135-155 kb) of synteny and conserved gene order, which may contain all of the elements r...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/10.4.371
更新日期:2001-02-15 00:00:00