Abstract:
:Microsatellites--tandem repeats of short DNA motifs--are abundant in the human genome and have high mutation rates. While microsatellite instability is implicated in numerous genetic diseases, the molecular processes involved in their emergence and disappearance are still not well understood. Microsatellites are hypothesized to follow a life cycle, wherein they are born and expand into adulthood, until their degradation and death. Here we identified microsatellite births/deaths in human, chimpanzee, and orangutan genomes, using macaque and marmoset as outgroups. We inferred mutations causing births/deaths based on parsimony, and investigated local genomic environments affecting them. We also studied birth/death patterns within transposable elements (Alus and L1s), coding regions, and disease-associated loci. We observed that substitutions were the predominant cause for births of short microsatellites, while insertions and deletions were important for births of longer microsatellites. Substitutions were the cause for deaths of microsatellites of virtually all lengths. AT-rich L1 sequences exhibited elevated frequency of births/deaths over their entire length, while GC-rich Alus only in their 3' poly(A) tails and middle A-stretches, with differences depending on transposable element integration timing. Births/deaths were strongly selected against in coding regions. Births/deaths occurred in genomic regions with high substitution rates, protomicrosatellite content, and L1 density, but low GC content and Alu density. The majority of the 17 disease-associated microsatellites examined are evolutionarily ancient (were acquired by the common ancestor of simians). Our genome-wide investigation of microsatellite life cycle has fundamental applications for predicting the susceptibility of birth/death of microsatellites, including many disease-causing loci.
journal_name
Genome Resjournal_title
Genome researchauthors
Kelkar YD,Eckert KA,Chiaromonte F,Makova KDdoi
10.1101/gr.122937.111subject
Has Abstractpub_date
2011-12-01 00:00:00pages
2038-48issue
12eissn
1088-9051issn
1549-5469pii
gr.122937.111journal_volume
21pub_type
杂志文章相关文献
GENOME RESEARCH文献大全abstract::Large terminal fragments of human chromosomes 2p, 6p, 8q, 12q, and 18q were cloned using yeast artificial chromosomes (YACs). RecA-assisted restriction endonuclease (RARE) cleavage analysis of genomic DNA samples from II unrelated individuals using YAC-derived probes confirmed the telomeric localizations of the half-Y...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.5.3.225
更新日期:1995-10-01 00:00:00
abstract::Mutational analysis of large genes with complex genomic structures plays an important role in medical genetics. Technical limitations associated with current mutation screening protocols have placed increased emphasis on the development of new technologies to simplify these procedures. High-density arrays of >90,000-o...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.8.12.1245
更新日期:1998-12-01 00:00:00
abstract::To elucidate the role of exon shuffling in shaping the complexity of the human genome/proteome, we have systematically analyzed intron phase distributions in the coding sequence of human protein domains. We found that introns at the boundaries of domains show high excess of symmetrical phase combinations (i.e., 0-0, 1...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.520702
更新日期:2002-11-01 00:00:00
abstract::Cys2-His2 zinc finger proteins (ZFPs) are the largest group of transcription factors in higher metazoans. A complete characterization of these ZFPs and their associated target sequences is pivotal to fully annotate transcriptional regulatory networks in metazoan genomes. As a first step in this process, we have charac...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.151472.112
更新日期:2013-06-01 00:00:00
abstract::To accelerate the molecular analysis of behavior in the honey bee (Apis mellifera), we created expressed sequence tag (EST) and cDNA microarray resources for the bee brain. Over 20,000 cDNA clones were partially sequenced from a normalized (and subsequently subtracted) library generated from adult A. mellifera brains....
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.5302
更新日期:2002-04-01 00:00:00
abstract::Cancer progression in humans is difficult to infer because we do not routinely sample patients at multiple stages of their disease. However, heterogeneous breast tumors provide a unique opportunity to study human tumor progression because they still contain evidence of early and intermediate subpopulations in the form...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.099622.109
更新日期:2010-01-01 00:00:00
abstract::There are numerous examples from the genomes of viruses, mitochondria, and chromosomes that adjacent genes can overlap, sharing at least one nucleotide. Overlaps have been hypothesized to be involved in genome size minimization and as a regulatory mechanism of gene expression. Here we show that overlapping genes are a...
journal_title:Genome research
pub_type: 信件
doi:10.1101/gr.2433104
更新日期:2004-11-01 00:00:00
abstract::Nucleosomes containing the CenH3 (CENPA or CENP-A) histone variant replace H3 nucleosomes at centromeres to provide a foundation for kinetochore assembly. CENPA nucleosomes are part of the constitutive centromere associated network (CCAN) that forms the inner kinetochore on which outer kinetochore proteins assemble. T...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.204784.116
更新日期:2016-09-01 00:00:00
abstract::Animal microRNA sequences are subject to 3' nucleotide addition. Through detailed analysis of deep-sequenced short RNA data sets, we show adenylation and uridylation of miRNA is globally present and conserved across Drosophila and vertebrates. To better understand 3' adenylation function, we deep-sequenced RNA after k...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.106054.110
更新日期:2010-10-01 00:00:00
abstract::The regulation of gene expression is mediated at the transcriptional level by enhancer regions that are bound by sequence-specific transcription factors (TFs). Recent studies have shown that the in vivo binding sites of single TFs differ between developmental or cellular contexts. How this context-specific binding is ...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.132811.111
更新日期:2012-10-01 00:00:00
abstract::Many CpG islands have tissue-dependent and differentially methylated regions (T-DMRs) in normal cells and tissues. To elucidate how DNA methyltransferases (Dnmts) participate in methylation of the genomic components, we investigated the genome-wide DNA methylation pattern of the T-DMRs with Dnmt1-, Dnmt3a-, and/or Dnm...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.2431504
更新日期:2004-09-01 00:00:00
abstract::Current generation DNA sequencing instruments are moving closer to seamlessly sequencing genomes of entire populations as a routine part of scientific investigation. However, while significant inroads have been made identifying small nucleotide variation and structural variations in DNA that impact phenotypes of inter...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.136739.111
更新日期:2013-01-01 00:00:00
abstract::Advanced prostate cancer can progress to systemic metastatic tumors, which are generally androgen insensitive and ultimately lethal. Here, we report a comprehensive genomic survey for somatic events in systemic metastatic prostate tumors using both high-resolution copy number analysis and targeted mutational survey of...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.107961.110
更新日期:2011-01-01 00:00:00
abstract::The last 20 years have been a remarkable era for biology and medicine. One of the most significant achievements has been the sequencing of the first human genomes, which has laid the foundation for profound insights into human genetics, the intricacies of regulation and development, and the forces of evolution. Incred...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.191684.115
更新日期:2015-10-01 00:00:00
abstract::Genes with sex-biased expression in Drosophila are thought to underlie sexually dimorphic phenotypes and have been shown to possess unique evolutionary properties. However, the forces and constraints governing the evolution of sex-biased genes in the somatic tissues of Drosophila are largely unknown. By using populati...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.259069.119
更新日期:2020-06-01 00:00:00
abstract::Interactions mediated by cell surface receptors initiate important instructive signaling cues but can be difficult to detect in biochemical assays because they are often highly transient and membrane-embedded receptors are difficult to solubilize in their native conformation. Here, we address these biochemical challen...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.231183.117
更新日期:2018-09-01 00:00:00
abstract::Drosophila melanogaster plays an important role in molecular, genetic, and genomic studies of heredity, development, metabolism, behavior, and human disease. The initial reference genome sequence reported more than a decade ago had a profound impact on progress in Drosophila research, and improving the accuracy and co...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.185579.114
更新日期:2015-03-01 00:00:00
abstract::Structured elements of RNA molecules are essential in, e.g., RNA stabilization, localization, and protein interaction, and their conservation across species suggests a common functional role. We computationally screened vertebrate genomes for conserved RNA structures (CRSs), leveraging structure-based, rather than seq...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.208652.116
更新日期:2017-08-01 00:00:00
abstract::Large copy number variants (CNVs) have been recently found as structural polymorphisms of the human genome of still unknown biological significance. CNVs are significantly enriched in regions with segmental duplications or low-copy repeats (LCRs). Williams-Beuren syndrome (WBS) is a neurodevelopmental disorder caused ...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.073197.107
更新日期:2008-05-01 00:00:00
abstract::Although changes in chromatin are integral to transcriptional reprogramming during cellular differentiation, it is currently unclear how chromatin modifications are targeted to specific loci. To systematically identify transcription factors (TFs) that can direct chromatin changes during cell fate decisions, we model t...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.142661.112
更新日期:2013-01-01 00:00:00
abstract::The use of high-density oligonucleotide arrays to measure the expression levels of thousands of genes in parallel has become commonplace. To take further advantage of the growing body of data, we developed a method, termed "GeSNP," to mine the detailed hybridization patterns in oligonucleotide array expression data fo...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.6307307
更新日期:2007-08-01 00:00:00
abstract::Short tandem repeats (STRs) have a wide range of applications, including medical genetics, forensics, and genetic genealogy. High-throughput sequencing (HTS) has the potential to profile hundreds of thousands of STR loci. However, mainstream bioinformatics pipelines are inadequate for the task. These pipelines treat S...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.135780.111
更新日期:2012-06-01 00:00:00
abstract::Long sequencing reads generated by single-molecule sequencing technology offer the possibility of dramatically improving the contiguity of genome assemblies. The biggest challenge today is that long reads have relatively high error rates, currently around 15%. The high error rates make it difficult to use this data al...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.213405.116
更新日期:2017-05-01 00:00:00
abstract::Maize (Zea mays L. ssp. mays), one of the most important agricultural crops in the world, originated by hybridization of two closely related progenitors. To investigate the fate of its genes after tetraploidization, we analyzed the sequence of five duplicated regions from different chromosomal locations. We also compa...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.2701104
更新日期:2004-10-01 00:00:00
abstract::Chromatin immunoprecipitation coupled with high-throughput sequencing (ChIP-seq) has become the dominant technique for mapping transcription factor (TF) binding regions genome-wide. We performed an integrative analysis centered around 457 ChIP-seq data sets on 119 human TFs generated by the ENCODE Consortium. We ident...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.139105.112
更新日期:2012-09-01 00:00:00
abstract::A large fraction of the genes from sequenced organisms are of unknown function. This limits biological insight, and for pathogenic microorganisms hampers the development of new approaches to battle infections. There is thus a great need for novel strategies that link genotypes to phenotypes for microorganisms. We desc...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.137430.112
更新日期:2012-12-01 00:00:00
abstract::Spatial organization of different epigenomic marks was used to infer functions of the epigenome. It remains unclear what can be learned from the temporal changes of the epigenome. Here, we developed a probabilistic model to cluster genomic sequences based on the similarity of temporal changes of multiple epigenomic ma...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.144949.112
更新日期:2013-02-01 00:00:00
abstract::Chromosomal aberrations have been thought to be random events. However, recent findings introduce a new paradigm in which certain DNA segments have the potential to adopt unusual conformations that lead to genomic instability and nonrandom chromosomal rearrangement. One of the best-studied examples is the palindromic ...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.079244.108
更新日期:2009-02-01 00:00:00
abstract::Short tandem repeats (STRs) are implicated in dozens of human genetic diseases and contribute significantly to genome variation and instability. Yet profiling STRs from short-read sequencing data is challenging because of their high sequencing error rates. Here, we developed STR-FM, short tandem repeat profiling using...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.185892.114
更新日期:2015-05-01 00:00:00
abstract::A machine that employs a novel reagent delivery technique for biomolecular synthesis has been developed. This machine separates the addressing of individual synthesis sites from the actual process of reagent delivery by using masks placed over the sites. Because of this separation, this machine is both cost-effective ...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.359002
更新日期:2002-12-01 00:00:00