We directly sequenced cell-free DNA with high-throughput shotgun sequencing technology from plasma of pregnant women, obtaining, on average, 5 million sequence tags per patient sample. This enabled us to measure the over-and underrepresentation of chromosomes from an aneuploid fetus. The sequencing approach is polymorphismindependent and therefore universally applicable for the noninvasive detection of fetal aneuploidy. Using this method, we successfully identified all nine cases of trisomy 21 (Down syndrome), two cases of trisomy 18 (Edward syndrome), and one case of trisomy 13 (Patau syndrome) in a cohort of 18 normal and aneuploid pregnancies; trisomy was detected at gestational ages as early as the 14th week. Direct sequencing also allowed us to study the characteristics of cell-free plasma DNA, and we found evidence that this DNA is enriched for sequences from nucleosomes.fetal DNA ͉ next-generation sequencing ͉ noninvasive prenatal diagnosis ͉ Down syndrome ͉ trisomy

Therapeutic proteins and antibodies represent a $125 billion annual market. Chinese Hamster Ovary (CHO) derived cell lines are the preferred host cells for the production of therapeutic proteins. Here, we present a draft genomic sequence of the CHO-K1 ancestral cell line. The assembly comprises 2.45Gb genomic sequence with 24,383 predicted genes. We associate most scaffolds to 21 microfluidically-isolated chromosomes to identify chromosomal locations of genes. Furthermore, we investigate genes involved in glycosylation, which affects therapeutic protein quality, and viral susceptibility genes, which affect cell engineering and regulatory concerns. Specifically, homologs for most human glycosylation-associated genes are identified in the CHO-K1 genome, although 141 are not expressed under exponential growth. In addition, many important viral entry genes are present in the genome but not expressed, which may explain the unusual viral resistance property of CHO cell lines. We demonstrate how the availability of this genome sequence may facilitate genome-scale science for biopharmaceutical protein production.

SUMMARY Meiotic recombination and de novo mutation are the two main contributions towards gamete genome diversity, and many questions remain about how an individual human’s genome is edited by these two processes. Here, we describe a high-throughput method for single-cell whole-genome analysis which was used to measure the genomic diversity in one individual’s gamete genomes. A microfluidic system was used for highly parallel sample processing and to minimize non-specific amplification. High-density genotyping results from 91 single cells were used to create a personal recombination map, which was consistent with population-wide data at low resolution but revealed significant differences from pedigree data at higher resolution. We used the data to test for meiotic drive and found evidence for gene conversion. High throughput sequencing on 31 single cells was used to measure the frequency of large-scale genome instability, and deeper sequencing of eight single cells revealed de novo mutation rates with distinct characteristics.