Increased genomic integrity of an improved protein-based mouse induced pluripotent stem cell method compared with current viral-induced strategies.

It has recently been shown that genomic integrity (with respect to copy number variants [CNVs]) is compromised in human induced pluripotent stem cells (iPSCs) generated by viral-based ectopic expression of specific transcription factors (e.g., Oct4, Sox2, Klf4, and c-Myc).

Analysis of variable retroduplications in human populations suggests coupling of retrotransposition to cell division.

In primates and other animals, reverse transcription of mRNA followed by genomic integration creates retroduplications. Expressed retroduplications are either "retrogenes" coding for functioning proteins, or expressed "processed pseudogenes," which can function as noncoding RNAs. To date, little is known about the variation in retroduplications in terms of their presence or absence across individuals in the human population.

Primate genome architecture influences structural variation mechanisms and functional consequences.

Although nucleotide resolution maps of genomic structural variants (SVs) have provided insights into the origin and impact of phenotypic diversity in humans, comparable maps in nonhuman primates have thus far been lacking. Using massively parallel DNA sequencing, we constructed fine-resolution genomic structural variation maps in five chimpanzees, five orang-utans, and five rhesus macaques. The SV maps, which are comprised of thousands of deletions, duplications, and mobile element insertions, revealed a high activity of retrotransposition in macaques compared with great apes.

Balancing selection on a regulatory region exhibiting ancient variation that predates human-neandertal divergence.

Ancient population structure shaping contemporary genetic variation has been recently appreciated and has important implications regarding our understanding of the structure of modern human genomes. We identified a ∼36-kb DNA segment in the human genome that displays an ancient substructure. The variation at this locus exists primarily as two highly divergent haplogroups.

Regulatory element copy number differences shape primate expression profiles.

Gene expression differences are shaped by selective pressures and contribute to phenotypic differences between species. We identified 964 copy number differences (CNDs) of conserved sequences across three primate species and examined their potential effects on gene expression profiles. Samples with copy number different genes had significantly different expression than samples with neutral copy number.

Landscape of somatic retrotransposition in human cancers.

Transposable elements (TEs) are abundant in the human genome, and some are capable of generating new insertions through RNA intermediates. In cancer, the disruption of cellular mechanisms that normally suppress TE activity may facilitate mutagenic retrotranspositions. We performed single-nucleotide resolution analysis of TE insertions in 43 high-coverage whole-genome sequencing data sets from five cancer types.

Exploring the role of copy number variants in human adaptation.

Over the past decade, the ubiquity of copy number variants (CNVs, the gain or loss of genomic material) in the genomes of healthy humans has become apparent. Although some of these variants are associated with disorders, a handful of studies documented an adaptive advantage conferred by CNVs. In this review, we propose that CNVs are substrates for human evolution and adaptation.

Refinement of primate copy number variation hotspots identifies candidate genomic regions evolving under positive selection.

Background: Copy number variants (CNVs), defined as losses and gains of segments of genomic DNA, are a major source of genomic variation.

Results: In this study, we identified over 2,000 human CNVs that overlap with orthologous chimpanzee or orthologous macaque CNVs. Of these, 170 CNVs overlap with both chimpanzee and macaque CNVs, and these were collapsed into 34 hotspot regions of CNV formation.

Natural mutagenesis of human genomes by endogenous retrotransposons.

Two abundant classes of mobile elements, namely Alu and L1 elements, continue to generate new retrotransposon insertions in human genomes. Estimates suggest that these elements have generated millions of new germline insertions in individual human genomes worldwide. Unfortunately, current technologies are not capable of detecting most of these young insertions, and the true extent of germline mutagenesis by endogenous human retrotransposons has been difficult to examine.

Which transposable elements are active in the human genome?

Although a large proportion (44%) of the human genome is occupied by transposons and transposon-like repetitive elements, only a small proportion (<0.05%) of these elements remain active today. Recent evidence indicates that approximately 35-40 subfamilies of Alu, L1 and SVA elements (and possibly HERV-K elements) remain actively mobile in the human genome.

Recently mobilized transposons in the human and chimpanzee genomes.

Transposable genetic elements are abundant in the genomes of most organisms, including humans. These endogenous mutagens can alter genes, promote genomic rearrangements, and may help to drive the speciation of organisms. In this study, we identified almost 11,000 transposon copies that are differentially present in the human and chimpanzee genomes.

Changes in mumps virus neurovirulence phenotype associated with quasispecies heterogeneity.

Mumps virus is a highly neurotropic virus with evidence of central nervous system invasion (CNS) in approximately half of all cases of infection. In countries where live attenuated mumps virus vaccines were introduced, the number of mumps cases declined dramatically; however, recently, the safety of some vaccine strains has been questioned. For example, one of the most widely used vaccines, the Urabe AM9 strain, was causally associated with meningitis, leading to the withdrawal of this product from the market in several countries.

Serological and phylogenetic evidence of monotypic immune responses to different mumps virus strains.

The recent resurgence of mumps epidemics in many countries with ongoing vaccination programs along with evidence of antigenic diversity among mumps virus strains have recently challenged the assumption that mumps virus is serologically monotypic. To address this controversy, we sought to identify two mumps virus strains that would best represent different serotypes, should multiple serotypes exist, and assess the ability of human sera to neutralize both strains. The virus strains, Enders and Lo1, were selected based upon a phylogenetic analysis of the major target of neutralizing antibody, the viral hemagglutinin-neuraminidase (HN) protein, along with data reported by others indicating that (1) these viruses are antigenically distinct and (2) genotypically similar strains have been implicated in cases of reinfection.