Dependence of intrachromosomal recombination in mammalian cells on uninterrupted homology.

Waldman, Alan S.; Liskay, R. Michael

doi:10.1128/mcb.8.12.5350

Cited by 222 publications

(177 citation statements)

References 22 publications

Supporting

Mentioning

168

Contrasting

Unclassified

Order By: Relevance

“…Because all crossovers occur in long stretches of identity, the minimum efficient processing segment (MEPS) for efficient meiotic homologous recombination was proposed to be between 337 and 456 bp long. This is similar to other observations of an ∼200 bp MEPS for homologous recombination in mammalian cells (Waldman and Liskay 1988). The finding of a mariner transposon-like element with its 3Ј end 1774 bp from the hot spot led to a hypothesis that it could mediate strand exchange events via doublestrand breaks induced by a transposase at or near the 3Ј end of the element (Reiter et al 1996(Reiter et al , 1998.…”

Section: Wwwgenomeorgsupporting

confidence: 70%

Structure of Chromosomal Duplicons and their Role in Mediating Human Genomic Disorders

Ji¹,

Eichler²,

Schwartz³

et al. 2000

Genome Res.

231

158

View full text Add to dashboard Cite

Chromosome-specific low-copy repeats, or duplicons, occur in multiple regions of the human genome. Homologous recombination between different duplicon copies leads to chromosomal rearrangements, such as deletions, duplications, inversions, and inverted duplications, depending on the orientation of the recombining duplicons. When such rearrangements cause dosage imbalance of a developmentally important gene(s), genetic diseases now termed genomic disorders result, at a frequency of 0.7–1/1000 births. Duplicons can have simple or very complex structures, with variation in copy number from 2 to >10 repeats, and each varying in size from a few kilobases in length to hundreds of kilobases. Analysis of the different duplicons involved in human genomic disorders identifies features that may predispose to recombination, including large size and high sequence identity between the recombining copies, putative recombination promoting features, and the presence of multiple genes/pseudogenes that may include genes expressed in germ cells. Most of the chromosome rearrangements involve duplicons near pericentromeric regions, which may relate to the propensity of such regions to accumulate duplicons. Detailed analyses of the structure, polymorphic variation, and mechanisms of recombination in genomic disorders, as well as the evolutionary origin of various duplicons will further our understanding of the structure, function, and fluidity of the human genome.

show abstract

Section: Wwwgenomeorgsupporting

confidence: 70%

Structure of Chromosomal Duplicons and their Role in Mediating Human Genomic Disorders

Ji¹,

Eichler²,

Schwartz³

et al. 2000

Genome Res.

231

158

View full text Add to dashboard Cite

show abstract

“…These studies also challenge the notion of minimum pairing segments of uninterrupted homology required for such exchanges (38)(39)(40). Finally, direct comparisons of germ-line mutation rates and population frequencies can provide insights into historical levels of selection operating in human populations.…”

Section: Discussionmentioning

confidence: 99%

Processes of copy-number change in human DNA: The dynamics of α-globin gene deletion

Lam

Jeffreys²

2006

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Ectopic recombination between locally repeated DNA sequences is of fundamental importance in the evolution of gene families, generating copy-number variation in human DNA and often leading to pathological rearrangements. Despite its importance, little is known about the dynamics and processes of these unequal crossovers and the degree to which meiotic recombination plays a role in instability. We address this issue by using as a highly informative system the duplicated ␣-globin genes in which ectopic recombination can lead to gene deletions, often very prevalent in populations affected by malaria, as well as reduplications. Here we show that spontaneous deletions can be accessed directly in genomic DNA by using single-DNA-molecule methods. These deletions proved to be remarkably common in both blood and sperm. Somatic deletions arise by a strictly intrachromosomal pathway of homologous exchange that also operates in the germ line and can generate mutational mosaicism, whereas sperm deletions frequently involve recombinational interactions between homologous chromosomes that most likely occur at meiosis. Ectopic recombination frequencies show surprisingly little requirement for long, identical homology blocks shared by paralogous sequences, and exchanges can occur even between short regions of sequence identity. Finally, direct knowledge of germ-line deletion rates can give insights into the fitness of individuals with these ␣-globin gene deletions, providing a new approach to investigating historical levels of selection operating in human populations.ectopic ͉ recombination ͉ selection ͉ mutation ͉ mosaicism

show abstract

“…LINE-1 elements located among high concentrations of such Alu elements might be rendered euchromatic. Since efficiency of illegitimate homologous recombination increases with length of homology (Waldman and Liskay, 1988;Baker et al, 1996), this would engender genome instability via illegitimate homologous recombination and possibly also via transposition if the element is suitably intact (Baker et al, 1996;Ostertag and Kazazian, 2001;Robertson, 2001). We would expect the genome instability engendered by euchromatic LINE-1 elements to result in these elements' being selected against.…”

Section: Non-random Repeat Distributions Via Natural Selectionmentioning

confidence: 99%

Repetitive sequence environment distinguishes housekeeping genes

Eller¹,

Regelson²,

Merriman³

et al. 2007

Gene

View full text Add to dashboard Cite

Housekeeping genes are expressed across a wide variety of tissues. Since repetitive sequences have been reported to influence the expression of individual genes, we employed a novel approach to determine whether housekeeping genes can be distinguished from tissue-specific genes their repetitive sequence context. We show that Alu elements are more highly concentrated around housekeeping genes while various longer (>400-bp) repetitive sequences ("repeats"), including Long Interspersed Nuclear Element 1 (LINE-1) elements, are excluded from these regions. We further show that isochore membership does not distinguish housekeeping genes from tissue-specific genes and that repetitive sequence environment distinguishes housekeeping genes from tissue-specific genes in every isochore. The distinct repetitive sequence environment, in combination with other previously published sequence properties of housekeeping genes, were used to develop a method of predicting housekeeping genes on the basis of DNA sequence alone. Using expression across tissue types as a measure of success, we demonstrate that repetitive sequence environment is by far the most important sequence feature identified to date for distinguishing housekeeping genes.

show abstract

Dependence of intrachromosomal recombination in mammalian cells on uninterrupted homology.

Abstract: Recombination between a 360-base-pair (bp) segment of a wild-type thymidine kinase gene (tk)

Cited by 222 publications

References 22 publications

Structure of Chromosomal Duplicons and their Role in Mediating Human Genomic Disorders

Structure of Chromosomal Duplicons and their Role in Mediating Human Genomic Disorders

Processes of copy-number change in human DNA: The dynamics of α-globin gene deletion

Repetitive sequence environment distinguishes housekeeping genes

Contact Info

Product

Resources

About