Česká Genetická Banka

SCIENCE: 21. 12. 2012

SCIENCE: Probing Meiotic Recombination and Aneuploidy of Single Sperm Cells by Whole-Genome Sequencing

"Meiotic recombination creates genetic diversity and ensures segregation of homologous chromosomes. Previous population analyses yielded results averaged among individuals and affected by evolutionary pressures. We sequenced 99 sperm from an Asian male by using the newly developed amplification method—multiple annealing and looping-based amplification cycles—to phase the personal genome and map recombination events at high resolution, which are nonuniformly distributed across the genome in the absence of selection pressure. The paucity of recombination near transcription start sites observed in individual sperm indicates that such a phenomenon is intrinsic to the molecular mechanism of meiosis. Interestingly, a decreased crossover frequency combined with an increase of autosomal aneuploidy is observable on a global per-sperm basis."

http://www.sciencemag.org/content/338/6114/1627.abstract?sid=aece5f76-ded6-4962-a032-93bc84b81c62

 

SCIENCE: Genome-Wide Detection of Single-Nucleotide and Copy-Number Variations of a Single Human Cell

"Kindred cells can have different genomes because of dynamic changes in DNA. Single-cell sequencing is needed to characterize these genomic differences but has been hindered by whole-genome amplification bias, resulting in low genome coverage. Here, we report on a new amplification method—multiple annealing and looping-based amplification cycles (MALBAC)—that offers high uniformity across the genome. Sequencing MALBAC-amplified DNA achieves 93% genome coverage ≥1x for a single human cell at 25x mean sequencing depth. We detected digitized copy-number variations (CNVs) of a single cancer cell. By sequencing three kindred cells, we were able to identify individual single-nucleotide variations (SNVs), with no false positives detected. We directly measured the genome-wide mutation rate of a cancer cell line and found that purine-pyrimidine exchanges occurred unusually frequently among the newly acquired SNVs."

http://www.sciencemag.org/content/338/6114/1622.abstract?sid=e035182a-cef4-42e9-a025-680bd554f141

 

SCIENCE: Evolutionary Dynamics of Gene and Isoform Regulation in Mammalian Tissues

"Most mammalian genes produce multiple distinct messenger RNAs through alternative splicing, but the extent of splicing conservation is not clear. To assess tissue-specific transcriptome variation across mammals, we sequenced complementary DNA from nine tissues from four mammals and one bird in biological triplicate, at unprecedented depth. We find that while tissue-specific gene expression programs are largely conserved, alternative splicing is well conserved in only a subset of tissues and is frequently lineage-specific. Thousands of previously unknown, lineage-specific, and conserved alternative exons were identified; widely conserved alternative exons had signatures of binding by MBNL, PTB, RBFOX, STAR, and TIA family splicing factors, implicating them as ancestral mammalian splicing regulators. Our data also indicate that alternative splicing often alters protein phosphorylatability, delimiting the scope of kinase signaling."

http://www.sciencemag.org/content/338/6114/1593.abstract?sid=0c4058cb-ca88-4a2f-81a4-b6bdea921d94

 

NATURE: Cardiovascular biology: A boost for heart regeneration

"Heart muscle cells die en masse after injury, yet the adult mammalian heart retains little capacity to regenerate them. Regulatory microRNA sequences may stimulate self-renewal of these muscle cells."

http://www.nature.com/nature/journal/v492/n7429/full/nature11763.html

 

NATURE: Somatic copy number mosaicism in human skin revealed by induced pluripotent stem cells

"Reprogramming somatic cells into induced pluripotent stem cells (iPSCs) has been suspected of causing de novo copy number variation. To explore this issue, here we perform a whole-genome and transcriptome analysis of 20 human iPSC lines derived from the primary skin fibroblasts of seven individuals using next-generation sequencing. We find that, on average, an iPSC line manifests two copy number variants (CNVs) not apparent in the fibroblasts from which the iPSC was derived...."

http://www.nature.com/nature/journal/v492/n7429/full/nature11629.html

 

NATURE: Tet1 controls meiosis by regulating meiotic gene expression

"Meiosis is a germ-cell-specific cell division process through which haploid gametes are produced for sexual reproduction¹. Before the initiation of meiosis, mouse primordial germ cells undergo a series of epigenetic reprogramming steps^{2, 3}, including the global erasure of DNA methylation at the 5-position of cytosine (5mC) in CpG-rich DNA^{4, 5}. Although several epigenetic regulators, such as Dnmt3l and the histone methyltransferases G9a and Prdm9, have been reported to be crucial for meiosis⁶, little is known about how the expression of meiotic genes is regulated and how their expression contributes to normal meiosis. ..."

http://www.nature.com/nature/journal/v492/n7429/full/nature11709.html