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Current
Genomics
ISSN: 1389-2029
Current Genomics
Volume 7, Number 1, March 2006
Contents
The Molecular Genetics of Migraine: Toward the Identification
of Responsible Genes Pp.1-10
F. Gianfrancesco and T. Esposito
[Abstract]
Microarrays in Brain Research: Data Quality and
Limitations Revisited Pp. 11-17
K. Mirnics
[Abstract]
The Critical Role of Insulin-Like Growth Factor-1
Isoforms in the Physiopathology of Skeletal Muscle Pp.
19-32
A. Musarò and N. Rosenthal
[Abstract]
Transgenic Plants Expressing Bacterial Genes as a
Model System for Plant Functional Genomics Pp. 33-42
E.S. Piruzian, I.V. Goldenkova-Pavlova, R.M.
Abdeev, R.A. Komakhin, S.A. Brouskin and I.A. Abdeeva
[Abstract]
Fish Genomes, Comparative Genomics and Vertebrate
Evolution Pp. 43-57
A. Froschauer, I. Braasch and J.-N. Volff
[Abstract]
Detecting Sequence-Sequence Interactions for Complex
Diseases Pp. 59-72
M. Lin and R. Wu
[Abstract]
Abstracts
[Back to top]
The Molecular Genetics of Migraine: Toward the Identification
of Responsible Genes
F. Gianfrancesco and T. Esposito
Migraine is a complex debilitating neurovascular
disease affecting approximately 15% of the Western populations.
Familial clustering, twin studies and segregation analyses
suggest that migraine has a significant genetic component,
but the number of genes involved remains unclear. The progress
in migraine genetics has recently jumped ahead with the identification
of genes responsible for Familiar Hemiplegic Migraine (FHM),
a rare subtype of migraine with aura showing autosomal dominant
mode of inheritance.
Nevertheless, the knowledge about common types of migraine
has been particularly rewarding and recently, seven loci with
significant linkage to migraine with or without aura have
been identified on 1q31, 4q24, 6p12.2-21.1, 11q24, 14q21.2-q22.3,
15q11-q13 and Xq24-28, suggesting the presence of migraine
susceptibility genes in these regions.
Identification of genes predisposing to the more common and
genetically complex forms of migraine has been complicated
by clinical and genetic heterogeneity of the disease. The
major challenge in the coming years facing biomedical research
of migraine is the identification of disease-susceptibility
genes and the understanding of how migraine risk can be influenced
by the interaction of these variants with each other and with
specific environmental factors in order to provide individuals
with clinically-useful diagnostic, prognostic and therapeutic
information. This paper briefly summarizes the previous knowledge
and highlights some recent developments in the complex genetic
nature of migraine.
[Back to top]
Microarrays in Brain Research: Data Quality and Limitations
Revisited
K. Mirnics
As predicted, in the post-genomic era
microarray technology has a major impact on our understanding
of complex gene expression patterns and circuit function in
the brain. We increasingly appreciate that, due to the phenotypic
and transcript complexity, brain transcriptome profiling data
are multifaceted and are best interpreted in the context of
the cellular diversity of the studied brain region. However,
despite advances made over the past five years, biological
interpretation of massive microarray datasets remains a significant
challenge. Although we are becoming more efficient in separating
“true” transcriptome differences from experimental
noise, verification of microarray data and anatomical localization
of expression changes to neuronal subpopulations will continue
to be an integral part of brain microarray experiments.
[Back to top]
The Critical Role of Insulin-Like Growth Factor-1
Isoforms in the Physiopathology of Skeletal Muscle
A. Musarò and N. Rosenthal
The prolongation of skeletal muscle
strength in aging and neuromuscular disease has been the objective
of numerous studies employing a variety of approaches. To
date however, efforts to prevent or attenuate age- or disease-related
muscle degeneration have been largely unsuccessful. Cell-based
therapies have been stalled by the difficulty in obtaining
sufficient numbers of autologous myoblasts and by inefficient
incorporation into host muscle. Administration of growth hormone
prevents age-related loss of muscle mass, but has failed to
increase muscle strength. In this context, where direct therapeutic
approaches to redress the primary disease are still suboptimal,
it may be more effective to focus on strategies for improving
skeletal muscle function.
Experimental models of muscle growth and regeneration have
implicated Insulin-like Growth Factor-1 (IGF-1) as an important
mediator of anabolic pathways in skeletal muscle cells. Two
major IGF-1 transcripts are characterized: the locally acting
isoform with an autocrine/paracrine action and the circulating
isoform with endocrine effects. The physiological differences
between the function of local and circulating isoform of IGF-1
are not completely established. However the selective expression
of the muscle-specific IGF-1 isoform avoids hypertrophic effects
on distal organs such as the heart, and eliminates risk of
possible neoplasms induced by inappropriate high expression
levels of circulating IGF-1. In this review we discuss the
roles of IGF-1 isoforms in myogenesis and the potential therapeutic
role of local IGF-1 isoform on muscle aging and diseases.
[Back to top]
Transgenic Plants Expressing Bacterial Genes as a
Model System for Plant Functional Genomics
E.S. Piruzian, I.V. Goldenkova-Pavlova, R.M.
Abdeev, R.A. Komakhin, S.A. Brouskin and I.A. Abdeeva
The functional analysis of plant genes
employs various comprehensive approaches that include transcriptome
analysis using microchips, gene knockout, RNA interference,
and various experimental models. We have proposed a novel
experimental model approach for plant functional genomics.
It is based on creating and studying transgenic plants that
express bacterial genes which are functionally similar to
plant genes. The validity of this approach owes to the similarity
of basic pro- and eukaryotic metabolic pathways and gene networks
controlling the functioning of these organisms under normal
conditions and in response to abiotic and biotic stresses.
Our studies using molecular biology, physiology and biochemistry
methods have demonstrated adequateness of the proposed strategy.
It allows the modeling of processes taking place in the plant
cell and differential assessment of contribution of individual
enzymes. Our results indicate that the proposed approach is
highly effective for functional genomics, namely, for determining
the function of a gene product in vivo. The experimental
data can be further used as a basis for elaboration of gene
networks controlling particular physiological processes and
stress responses of plants to biotic and abiotic environmental
factors.
[Back to top]
Fish Genomes, Comparative Genomics and Vertebrate
Evolution
A. Froschauer, I. Braasch and J.-N. Volff
Genome sequences from the pufferfishes Takifugu rubripes
(Fugu) and Tetraodon nigroviridis, the zebrafish
Danio rerio and the medaka Oryzias latipes
together with genomic data from various other fish species
have opened an important era of comparative genomics shedding
a new light on the structure and evolution of vertebrate genomes.
For instance, comparative analysis of fish genomes has revealed
that the ancestral bony vertebrate genome was composed of
12 chromosomes, has confirmed the occurrence of at least one
event of genome duplication in the early history of vertebrates
and has allowed the identification of conserved regulatory
and coding sequences in the human genome. Importantly, major
differences have been observed between teleost fish and mammalian
genomes. There is now convincing evidence that all teleosts
are derived from a common tetraploid fish ancestor. This tetraploidization
event arose about 320-350 million years ago in the ray-finned
fish lineage, followed by rediploidization and retention of
hundreds of duplicate pairs. Divergent evolution of the resulting
duplicates has been proposed to be involved in the species
richness observed in teleost fishes. Fish genomes also contain
many more families of transposable elements than mammals and
birds. Finally, while the mammalian and bird lineages possess
major sex determination systems with sex chromosomes conserved
in very divergent species, fishes have very frequently switched
between sex determination mechanisms and repeatedly created
novel sex chromosomes during evolution. Hence, teleost fishes
display a high level of genomic plasticity, which might be
related to the astonishing biodiversity observed in these
animals.
[Back to top]
Detecting Sequence-Sequence Interactions for Complex
Diseases
M. Lin and R. Wu
Because of its paramount importance in many
biological and biomedical aspects, epistasis, expressed as
the suppression or enhancement of a gene by the effect of
an unrelated gene, has received a resurgence of interest in
recent years. One of the most powerful analytical approaches
for detecting epistasis is based on the genetic mapping of
interacting quantitative trait loci (QTL) that often present
long chromosomal segments. Current high-throughput technologies
for genotyping single nucleotide polymorphisms (SNPs) to construct
the haplotype map or HapMap for the entire human genome are
shaping our prospects into the role of epistasis. In this
article, we have developed a new statistical model for refining
QTL structure into individual nucleotides and estimating and
testing epistasis between different DNA nucleotides throughout
the HapMap. This model detects quantitative trait nucleotides
(QTN) for complex diseases. It is founded on the SNP-based
haplotype blocking theory, constructed within the context
of maximum likelihood and implemented with the EM algorithm.
The model provides a quantitative framework for testing the
additive ×
additive, additive ×
dominance, dominance ×
additive and dominance ×
dominance interaction effects between different QTN sequences
from haplotype blocks. The model was used to detect sequence-sequence
interactions between two candidate genes, BAR-1 and BAR-2,
for human obesity in 155 subjects sampled from a natural population.
This model will have many implications for the detection of
specific DNA sequence variants that interactively contribute
to the genetic architecture of complex diseases.
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