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Current
Genomics
ISSN: 1389-2029
Current Genomics
Volume 8, Number 3, May 2007
Contents
Meiosis-Driven Genome Variation in Plants
Pp. 151-161
X. Cai and S.S. Xu
[Abstract]
EGFR Intron Recombination in Human Gliomas: Inappropriate
Diversion of V(D)J Recombination? Pp. 163-170
R.A. Fenstermaker and M.J. Ciesielski
[Abstract]
Parallel Gene Expression Profiling of Mantle
Cell Lymphoma – How Do We Transform ´Omics Data
into Clinical Practice Pp. 171-179
S. Ek and C.A.K. Borrebaeck
[Abstract]
Gene Expression Studies in Multiple Sclerosis
Pp. 181-189
L. Tajouri, F. Fernandez and L.R. Griffiths
[Abstract]
Genetics of Bacterial Alginate: Alginate Genes
Distribution, Organization and Biosynthesis in Bacteria
Pp. 191-202
Muhammadi and N. Ahmed
[Abstract]
Megsin Gene: Its Genomic Analysis, Pathobiological
Functions, and Therapeutic Perspectives Pp. 203-208
T. Miyata, M. Li, X. Yu and N. Hirayama
[Abstract]
Abstracts
[Back to top]
Meiosis-Driven Genome Variation in Plants
X. Cai and S.S. Xu
Meiosis includes two successive divisions of the nucleus
with one round of DNA replication and leads to the formation
of gametes with half of the chromosomes of the mother cell
during sexual reproduction. It provides a cytological basis
for gametogenesis and inheritance in eukaryotes. Meiotic cell
division is a complex and dynamic process that involves a
number of molecular and cellular events, such as DNA and chromosome
replication, chromosome pairing, synapsis and recombination,
chromosome segregation, and cytokinesis. Meiosis maintains
genome stability and integrity over sexual life cycles. On
the other hand, meiosis generates genome variations in several
ways. Variant meiotic recombination resulting from specific
genome structures induces deletions, duplications, and other
rearrangements within the genic and non-genic genomic regions
and has been considered a major driving force for gene and
genome evolution in nature. Meiotic abnormalities in chromosome
segregation lead to chromosomally imbalanced gametes and aneuploidy.
Meiotic restitution due to failure of the first or second
meiotic division gives rise to unreduced gametes, which triggers
polyploidization and genome expansion. This paper reviews
research regarding meiosis-driven genome variation, including
deletion and duplication of genomic regions, aneuploidy, and
polyploidization, and discusses the effect of related meiotic
events on genome variation and evolution in plants. Knowledge
of various meiosis driven genome variations provides insight
into genome evolution and genetic variability in plants and
facilitates plant genome research.
[Back to top]
EGFR Intron Recombination in Human Gliomas: Inappropriate
Diversion of V(D)J Recombination?
R.A. Fenstermaker and M.J. Ciesielski
The epidermal growth factor receptor (EGFR) is a membrane
bound, 170 kDa, protein tyrosine kinase that plays an important
role in tumorigenesis. The EGFR gene, which is composed of
over 168 kb of sequence, including a 123-kb first intron,
is frequently amplified and rearranged in malignant gliomas
leading to the expression of oncogenic deletion (DM) and tandem
duplication (TDM) mutants. The most common DM in gliomas is
EGFRvIII, which arises from recombination between introns
1 and 7 with deletion of exons 2 through 7 and intervening
introns. In addition, some human gliomas express 180- to 190-kDa
TDM, which are constitutively active and highly oncogenic.
Both DM and TDM arise by recombination of introns that contain
sequences with homology to the recombination signal sequence
(RSS) heptamers and nonamers present in the V(D)J region of
the immunoglobin and T lymphocyte antigen receptor genes.
V(D)J RSS have also been identified in certain proto-oncogenes
like bcl-2 that are involved in translocations associated
with the development of human lymphomas and in other genes
such as hypoxanthine-guainine phosphoribosyl transferase (HPRT)
in which deletion mutations and intron rearrangements are
a common phenomenon. Together with the expression of recombination
associated gene (RAG) and nonhomologous end joining (NHEJ)
proteins in gliomas, these observation suggest that aberrant
activity of the V(D)J recombinase may be involved in the activation
of proto-oncogenes in both liquid and solid tumors.
[Back to top]
Parallel Gene Expression Profiling of Mantle
Cell Lymphoma – How Do We Transform ´Omics Data
into Clinical Practice
S. Ek and C.A.K. Borrebaeck
DNA microarray technology has been a valuable tool to
provide a global view of the changes in gene expression that
characterize different types of B cell lymphomas, both in
relation to clinical parameters but also in comparison with
the non-malignant counterparts. The number of transcripts
that can be analyzed on an array has dramatically increased,
and now most commercially available arrays cover the whole
genome, enabling overall analysis of the transcriptome. The
backside of collecting this massive amount of information
is that even after strict data filtering, it is impossible
to do follow-up studies on all findings. Down-stream analysis
is time-consuming and when performing confirmatory experiments
on the protein level, the experiments are in most cases restricted
to proteins recognized by commercially available reagents.
Furthermore, since gene expression data is a comparative method
not only are the experimental set-up but also the characteristics
of both the sample and reference crucial for our ability to
answer the questions posed. Thus, initial care must be taken
in the design of the experiment and the preparation of the
samples.
The aim of this review is to discuss the progress in mantle
cell lymphoma research enabled by gene expression analysis
and to pinpoint the difficulties in making efficient use of
the generated data to provide a fast and accurate clinical
diagnosis, efficient stratification of patients into disease
sub-groups and improved therapy.
[Back to top]
Gene Expression Studies in Multiple Sclerosis
L. Tajouri, F. Fernandez and L.R. Griffiths
Multiple sclerosis (MS) is a serious neurological disorder
affecting young Caucasian individuals, usually with an age
of onset at 18 to 40 years old. Females account for approximately
60% of MS cases and the manifestation and course of the disease
is highly variable from patient to patient. The disorder is
characterised by the development of plaques within the central
nervous system (CNS). Many gene expression studies have been
undertaken to look at the specific patterns of gene transcript
levels in MS. Human tissues and experimental mice were used
in these gene-profiling studies and a very valuable and interesting
set of data has resulted from these various expression studies.
In general, genes showing variable expression include mainly
immunological and inflammatory genes, stress and antioxidant
genes, as well as metabolic and central nervous system markers.
Of particular interest are a number of genes localised to
susceptible loci previously shown to be in linkage with MS.
However due to the clinical complexity of the disease, the
heterogeneity of the tissues used in expression studies, as
well as the variable DNA chips/membranes used for the gene
profiling, it is difficult to interpret the available information.
Although this information is essential for the understanding
of the pathogenesis of MS, it is difficult to decipher and
define the gene pathways involved in the disorder. Experiments
in gene expression profiling in MS have been numerous and
lists of candidates are now available for analysis. Researchers
have investigated gene expression in peripheral mononuclear
white blood cells (PBMCs), in MS animal models Experimental
Allergic Encephalomyelitis (EAE) and post mortem
MS brain tissues. This review will focus on the results of
these studies.
[Back to top]
Genetics of Bacterial Alginate: Alginate Genes
Distribution, Organization and Biosynthesis in Bacteria
Muhammadi and N. Ahmed
Bacterial alginate genes are chromosomal and fairly widespread
among rRNA homology group I Pseudomonads and Azotobacter.
In both genera, the genetic pathway of alginate biosynthesis
is mostly similar and the identified genes are identically
organized into biosynthetic, regulatory and genetic switching
clusters. In spite of these similarities, still there are
transcriptional and functional variations between P. aeruginosa
and A. vinelandii. In P. aeruginosa all
biosynthetic genes except algC transcribe in polycistronic
manner under the control of algD promoter while in
A. vinelandii, these are organized into many transcriptional
units. Of these, algA and algC are transcribed
each from two different and algD from three different promoters.
Unlike P. aeruginosa, the promoters of these transcriptional
units except one of algC and algD are algT-independent.
Both bacterial species carry homologous algG gene for Ca2+-independent
epimerization. But besides algG, A. vinelandii
also has algE1-7 genes which encode C-5-epimerases
involved in the complex steps of Ca2+-dependent
epimerization. A hierarchy of alginate genes expression under
σ22(algT)
control exists in P. aeruginosa where algT
is required for transcription of the response regulators algB
and algR, which in turn are necessary for expression
of algD and its downstream biosynthetic genes. Although
algTmucABCD genes cluster play similar regulatory
roles in both P. aeruginosa and A. vinelandii
but unlike, transcription of A. vinelandii, algR
is independent of σ22.
These differences could be due to the fact that in A.
vinelandii alginate plays a role as an integrated part
in desiccation-resistant cyst which is not found in P.
aeruginosa.
[Back to top]
Megsin Gene: Its Genomic Analysis, Pathobiological
Functions, and Therapeutic Perspectives
T. Miyata, M. Li, X. Yu and N. Hirayama
It is critical to uncover genes specifically expressed
in individual cell types for further understanding of cell
biology and pathology. In order to elucidate pathogenesis
of renal disease, we performed functional quantitative analysis
of the genome in human kidney cells and compared the expression
levels of a variety of kidney transcripts with those in other
non-kidney cells. As a result, we identified a novel human
gene, megsin, which is a new serine protease inhibitor (serpin)
predominantly expressed in the kidney. Megsin is up-regulated
in kidney disease. Genomic analysis revealed an association
of the polymorphisms of megsin gene with susceptibility and/or
progression of kidney disease. Its overexpression in rodents
has led to the recognition of two different kidney abnormalities.
The first disorder is linked to megsin biological effect itself
and the other to its conformational abnormality recently called
the serpinopathy. In the latter model, the cellular and tissue
damage is induced by the endoplasmic reticulum (ER) stress
due to conformational disorder resulting from megsin tertiary
structure. In both types, the inhibition of megsin’s
activity or abnormal conformational change should open new
therapeutic perspectives. The desire to prevent these abnormalities
with the hope to offer new therapeutic strategies has stimulated
the development of megsin inhibitors by a structure based
drug design approach relying on a precisely known three dimensional
megsin structure.
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