A 2.91-billion base pair (bp) consensus sequence of the euchromatic portion of the human genome was generated by the whole-genome shotgun sequencing method. The 14.8-billion bp DNA sequence was generated over 9 months from 27,271,853 high-quality sequence reads (5.11-fold coverage of the genome) from both ends of plasmid clones made from the DNA of five individuals. Two assembly strategies—a whole-genome assembly and a regional chromosome assembly—were used, each combining sequence data from Celera and the publicly funded genome effort. The public data were shredded into 550-bp segments to create a 2.9-fold coverage of those genome regions that had been sequenced, without including biases inherent in the cloning and assembly procedure used by the publicly funded group. This brought the effective coverage in the assemblies to eightfold, reducing the number and size of gaps in the final assembly over what would be obtained with 5.11-fold coverage. The two assembly strategies yielded very similar results that largely agree with independent mapping data. The assemblies effectively cover the euchromatic regions of the human chromosomes. More than 90% of the genome is in scaffold assemblies of 100,000 bp or more, and 25% of the genome is in scaffolds of 10 million bp or larger. Analysis of the genome sequence revealed 26,588 protein-encoding transcripts for which there was strong corroborating evidence and an additional ∼12,000 computationally derived genes with mouse matches or other weak supporting evidence. Although gene-dense clusters are obvious, almost half the genes are dispersed in low G+C sequence separated by large tracts of apparently noncoding sequence. Only 1.1% of the genome is spanned by exons, whereas 24% is in introns, with 75% of the genome being intergenic DNA. Duplications of segmental blocks, ranging in size up to chromosomal lengths, are abundant throughout the genome and reveal a complex evolutionary history. Comparative genomic analysis indicates vertebrate expansions of genes associated with neuronal function, with tissue-specific developmental regulation, and with the hemostasis and immune systems. DNA sequence comparisons between the consensus sequence and publicly funded genome data provided locations of 2.1 million single-nucleotide polymorphisms (SNPs). A random pair of human haploid genomes differed at a rate of 1 bp per 1250 on average, but there was marked heterogeneity in the level of polymorphism across the genome. Less than 1% of all SNPs resulted in variation in proteins, but the task of determining which SNPs have functional consequences remains an open challenge.

Cytogenetic abnormalities of chromosome 9p21 are characteristic of malignant melanomas, gliomas, lung cancers and leukaemias. From a panel of 46 human malignant cell lines, we localized by positional cloning the most frequently deleted region on 9p21. Sequence analysis of the isolated fragment reveals two open reading frames identical to the recently described complementary DNA for the inhibitor of cyclin-dependent kinase 4 (CDK4). Polymerase chain reaction and Southern blot analysis confirmed the frequent deletion or rearrangement of the CDK4-inhibitor gene in melanomas, gliomas, lung cancers and leukaemias, and the absence of detectable gene transcripts. One carcinoma had a deletion entirely within the CDK4-inhibitor gene. The CDK4-inhibitor gene from a patient with dysplastic nevus syndrome had a germ-line nonsense mutation. The CDK4 inhibitor is thought to be a physiological suppressor of proliferation. Cells unable to produce the inhibitor may be prone to neoplastic transformation.

Abstract-Reading text from photographs is a challenging problem that has received a significant amount of attention. Two key components of most systems are (i) text detection from images and (ii) character recognition, and many recent methods have been proposed to design better feature representations and models for both. In this paper, we apply methods recently developed in machine learning-specifically, large-scale algorithms for learning the features automatically from unlabeled data-and show that they allow us to construct highly effective classifiers for both detection and recognition to be used in a high accuracy end-to-end system.

A cluster of low copy repeats on the proximal long arm of chromosome 15 mediate various forms of stereotyped deletions and duplication events that cause a group of neurodevelopmental disorders that are associated with autism or autism spectrum disorders (ASD). The region is subject to genomic imprinting and the behavioral phenotypes associated with the chromosome 15q11.2-q13 disorders show a parent-of-origin specific effect that suggests that increased copy number of maternally derived alleles contributes to autism susceptibility. Notably, nonimprinted, biallellically expressed genes within the interval also have been shown to be misexpressed in brains of patients with chromosome 15q11.2-q13 genomic disorders, indicating that they also likely play a role in the phenotypic outcome. This review provides an overview of the phenotypes of these disorders and their relationships with ASD and outlines the regional genes that may contribute to the autism susceptibility imparted by copy number variation of the region. KeywordsAutism; Autism spectrum disorders; Prader Willi syndrome; Angelman Syndrome; Interstitial Duplication Chromosome 15; Isodicentric Chromosome 15; Low Copy Repeats; Imprinting The Complexities of the Genomic Landscape of Chromosome 15q11.2-q13Chromosome 15 has been identified as one of seven chromosomes enriched in segmental low copy repeats (LCRs) or duplicons (Bailey et al., 2002). These duplicons provide a mechanism in which LCR mediated misalignment during meiosis I leads to unequal nonallelic homologous recombination generating a series of common breakpoints (BPs) along the 15q11.2-q13 Robinson et al., 1993a;Robinson et al., 1998b;Robinson et al., 1993c).To whom all correspondence should be addressed: N. Carolyn Schanen, M.D., Ph.D., Nemours Biomedical Research, 1600 Rockland Road, Room RC1-241, Wilmington DE 19803, (302) 651 6702 phone, (302) 651 6767 Facsimile, schanen@medsci.udel.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptNeurobiol Dis. Author manuscript; available in PMC 2011 May 1. Published in final edited form as:Neurobiol Dis. 2010 May ; 38(2): 181-191. doi:10.1016/j.nbd.2008.011. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptThe proximal three BP correspond to complex LCRs ranging in size from 50 -400 kb and contain sequences derived from HERC2 and GOLGA8E loci (Amos-Landgraf et al., 1999;Ji et al., 2000;Makoff and Flomen, 2007) (Figure 1). While the actively transcribed HERC2 and GOLGA8E genes lie just centromeric to BP3 and BP1, respectively, numerous transcribed ps...

In an order-preserving encryption scheme, the encryption algorithm produces ciphertexts that preserve the order of their plaintexts. Order-preserving encryption schemes have been studied intensely in the last decade, and yet not much is known about the security of these schemes. Very recently, Boneh et al. (Eurocrypt 2015) introduced a generalization of order-preserving encryption, called order-revealing encryption, and presented a construction which achieves this notion with best-possible security. Because their construction relies on multilinear maps, it is too impractical for most applications and therefore remains a theoretical result.In this work, we build efficiently implementable order-revealing encryption from pseudorandom functions. We present the first efficient order-revealing encryption scheme which achieves a simulation-based security notion with respect to a leakage function that precisely quantifies what is leaked by the scheme. In fact, ciphertexts in our scheme are only about 1.6 times longer than their plaintexts. Moreover, we show how composing our construction with existing order-preserving encryption schemes results in order-revealing encryption that is strictly more secure than all preceding order-preserving encryption schemes.