Asian Science Citation Index is committed to provide an authoritative, trusted and significant information by the coverage of the most important and influential journals to meet the needs of the global scientific community.  
ASCI Database
308-Lasani Town,
Sargodha Road,
Faisalabad, Pakistan
Fax: +92-41-8815544
Contact Via Web
Suggest a Journal
 
Articles by H. J Jacob
Total Records ( 2 ) for H. J Jacob
  T Adamovic , D McAllister , V Guryev , X Wang , J. W Andrae , E Cuppen , H. J Jacob and S. L. Sugg
 

The presence of copy number variants in normal genomes poses a challenge to identify small genuine somatic copy number changes in high-resolution cancer genome profiling studies due to the use of unpaired reference DNA. Another problem is the well-known rearrangements of immunoglobulin and T-cell receptor genes in lymphocytes (a commonly used reference), which may misdirect the researcher to a locus with no relevance in tumorigenesis. We here show real gains of the IgG heavy chain V gene region in carcinogen-induced rat mammary tumor samples after normalization to paired mammary gland, a tissue without lymphocyte infiltration. We further show that the segmental duplication region encompassing the IgG heavy chain V genes is a copy number variant between the susceptible (SS) and the resistant (BN) to mammary tumor development inbred rat strains. Our data suggest that the already inherently unstable genomic region is a convenient target for additional structural rearrangements (gains) at the somatic level when exposed to a carcinogen (7,12-dimethylbenz[a]anthracene), which subsequently seem to benefit tumor development in the mammary gland of the susceptible strain. Thus, the selection of an appropriate reference DNA enabled us to identify immunoglobulin genes as novel cancer targets playing a role in mammary tumor development. We conclude that control DNA in array-based comparative genomic hybridization experiments should be selected with care, and DNA from pooled spleen (contains immature lymphocytes and is used as reference in animal studies) or blood may not be the ideal control in the study of primary tumors. [Cancer Res 2009;69(12):5159–67]

  L Lu , P Li , C Yang , T Kurth , M Misale , M Skelton , C Moreno , R. J Roman , A. S Greene , H. J Jacob , J Lazar , M Liang and A. W. Cowley
 

Chromosome 13 consomic and congenic rat strains were analyzed to investigate the pattern of genomic pathway utilization involved in protection against salt-sensitive hypertension and renal injury. Introgression of the entire Brown-Norway chromosome 13 (consomic SS-13BN) or nonoverlapping segments of this chromosome (congenic strains, 16 Mbp in D13Rat151–D13Rat197 or 14 Mbp in D13Rat111–D13Got22) into the genome of the Dahl salt-sensitive rat attenuated salt-induced hypertension and proteinuria. mRNA abundance profiles in the renal cortex and the renal medulla from rats receiving 0.4% or 8% NaCl diets revealed two important features of pathway recruitment in these rat strains. First, the two congenic strains shared alterations in several pathways compared with Dahl salt-sensitive rats, despite the fact that the genomic segments introgressed in the two congenic strains did not overlap. Second, even though the genomic segment introgressed in each congenic strain was a part of the chromosome introgressed in the consomic strain, pathways altered in each congenic strain were not simply a subset of those altered in the consomic. Supporting the relevance of the mRNA data, differential expression of oxidative stress-related genes among the four strains of rats was associated with differences in urinary excretion of lipid peroxidation products. The findings suggest that different genetic alterations might converge to influence shared pathways in protection from hypertension, and that, depending on the genomic context, the same genetic alteration might diverge to affect different pathways.

 
 
 
Copyright   |   Desclaimer   |    Privacy Policy   |   Browsers   |   Accessibility