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1 News 92 Publications 17 Members

VISTA: computational tools for comparative genomics.

Kelly A. Frazer Pachter, L Poliakov, A Rubin, Em Dubchak, I

Published in Nucleic Acids Research

Comparison of DNA sequences from different species is a fundamental method for identifying functional elements in genomes. Here, we describe the VISTA family of tools created to assist biologists in carrying out this task. Our first VISTA server at http://www-gsd.lbl.gov/vista/ was launched in the summer of 2000 and was designed to align long genom...

Active conservation of noncoding sequences revealed by three-way species comparisons.

Dubchak, I Brudno, M Loots, Gg Pachter, L Mayor, C Rubin, Em Kelly A. Frazer

Published in Genome Research

Human and mouse genomic sequence comparisons are being increasingly used to search for evolutionarily conserved gene regulatory elements. Large-scale human-mouse DNA comparison studies have discovered numerous conserved noncoding sequences of which only a fraction has been functionally investigated A question therefore remains as to whether most of...

A novel and rapid method for isolating sequences adjacent to rare cutting sites and their use in physical mapping.

Patel, K Cox, R Shipley, J Kiely, F Kelly A. Frazer Cox, Dr Lehrach, H Sheer, D

Published in Nucleic Acids Research

We describe a simple PCR based technique which can be used to isolate sequences adjacent to rare cutter sites and can subsequently be employed for the construction of long range physical maps. The method involves the ligation of an adaptor to rare cutter sequences and its use as a target for forward priming in PCR. Primers to Alu repeat elements in...

Computational and biological analysis of 680 kb of DNA sequence from the human 5q31 cytokine gene cluster region.

Kelly A. Frazer Ueda, Y Zhu, Y Gifford, Vr Garofalo, Mr Mohandas, N Martin, Ch Palazzolo, Mj Cheng, Jf Rubin, Em ...

Published in Genome Research

With the human genome project advancing into what will be a 7- to 10-year DNA sequencing phase, we are presented with the challenge of developing strategies to convert genomic sequence data, as they become available, into biologically meaningful information. We have analyzed 680 kb of noncontiguous DNA sequence from a 1-Mb region of human chromosom...

A Pan-BCL2 inhibitor renders bone-marrow-resident human leukemia stem cells sensitive to tyrosine kinase inhibition. PDF available through Get Fulltext Research

Goff, Dj Court Recart, A Sadarangani, A Chun, Hj Christian Barrett Krajewska, M Leu, H Low-Marchelli, J Ma, W Shih, Ay ...

Published in Cell Stem Cell

Leukemia stem cells (LSCs) play a pivotal role in the resistance of chronic myeloid leukemia (CML) to tyrosine kinase inhibitors (TKIs) and its progression to blast crisis (BC), in part, through the alternative splicing of self-renewal and survival genes. To elucidate splice-isoform regulators of human BC LSC maintenance, we performed whole-transcr...

Genomic DNA insertions and deletions occur frequently between humans and nonhuman primates.

Kelly A. Frazer Chen, X Hinds, Da Pant, Pv Patil, N Cox, Dr

Published in Genome Research

Comparative DNA sequence studies between humans and nonhuman primates will be important for understanding the genetic basis of the phenotypic differences between these species. Here we compare approximately 27 Mb of human chromosome 21 with chimpanzee DNA sequences identifying 57 genomic rearrangements (deletions and insertions ranging in size from...

The apolipoprotein(a) gene is regulated by sex hormones and acute-phase inducers in YAC transgenic mice.

Kelly A. Frazer Narla, G Zhang, Jl Rubin, Em

Published in Nature Genetics

High plasma concentrations of apolipoprotein (a) (apo(a)) have been implicated as a major independent risk factor for atherosclerosis in humans. Apo(a) is a large, evolutionarily new gene (present primarily in primates) for which considerable controversy exists concerning the factors that regulate its expression. To investigate the in vivo regulati...

High-resolution whole-genome association study of Parkinson disease.

Maraganore, Dm De Andrade, M Lesnick, Tg Strain, Kj Farrer, Mj Rocca, Wa Pant, Pv Kelly A. Frazer Cox, Dr Ballinger, Dg ...

Published in The American Journal of Human Genetics

We performed a two-tiered, whole-genome association study of Parkinson disease (PD). For tier 1, we individually genotyped 198,345 uniformly spaced and informative single-nucleotide polymorphisms (SNPs) in 443 sibling pairs discordant for PD. For tier 2a, we individually genotyped 1,793 PD-associated SNPs (P<.01 in tier 1) and 300 genomic control S...

Reversion to an embryonic alternative splicing program enhances leukemia stem cell self-renewal.

Holm, F Hellqvist, E Mason, Cn Ali, Sa Delos-Santos, N Christian Barrett Chun, Hj Minden, Md Moore, Ra Marra, Ma ...

Published in Proceedings of the National Academy of Sciences

Formative research suggests that a human embryonic stem cell-specific alternative splicing gene regulatory network, which is repressed by Muscleblind-like (MBNL) RNA binding proteins, is involved in cell reprogramming. In this study, RNA sequencing, splice isoform-specific quantitative RT-PCR, lentiviral transduction, and in vivo humanized mouse mo...

Functional screening of an asthma QTL in YAC transgenic mice.

Symula, Dj Kelly A. Frazer Ueda, Y Denefle, P Stevens, Me Wang, Ze Locksley, R Rubin, Em

Published in Nature Genetics

Many quantitative trait loci (QTLs) contributing to genetically complex conditions have been discovered, but few causative genes have been identified. This is mainly due to the large size of QTLs and the subtle connection between genotype and quantitative phenotype associated with these conditions. Transgenic mice have been successfully used to ana...

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