Current Genomics - Volume 6, Issue 7, 2005

The term epigenetics defines the heritable changes in gene expression that occur through changes in the chromatin structure, rather than changes in the DNA sequence. The methylation of cytosines (m5C) in CpG dinucleotides (DNA methylation) and the modification of histones are fundamental epigenetic mechanisms that regulate eukaryotic gene expression. In general, increases in DNA methylation are associated with gene sil Read More

The availability of complete genomes and global gene expression profiling has greatly facilitated analysis of complex genetic regulatory systems. We describe the use of a bioinformatics strategy for analyzing the cis-regulatory design of genes diferentially regulated during viral infection of a target cell. The large-scale transcriptional activity of human embryonic kidney (HEK293) cells to reovirus (serotype 3 Abney) infection w Read More

Fragile X syndrome is the most common inherited form of mental retardation and is due to the silencing of FMR1 gene coding for the FMRP protein. FMRP is an RNA binding protein endowed with Nuclear Localization and Nuclear Export Signals and is associated with actively translating polysomes as part of mRNP complexes. During the past years, efforts from many laboratories to unravel the function of this protein, resulted in the Read More

Many genes important during early development in vertebrates are regulated by sequences located at large distances from the protein coding region. Clues to the location of these long-range gene-regulatory elements can be obtained from comparing genomic sequences of evolutionarily distant species such as the mouse and human. However, identifying them functionally remains a major challenge. Analysis of distal regu Read More

First named Narc-1 (Neural apoptosis regulated convertase 1), PC9 is the ninth member of the family of proprotein convertases. This newly identified human subtilase contributes to cholesterol homeostasis and mutations in its gene, PCSK9 (Proprotein Convertase Subtilisin/Kexin type 9), are responsible for Autosomal Dominant Hypercholesterolemia. This is the first example of a dominant disease associated with a defect Read More

We review current approaches that can extend our understanding of monogenic disease towards complex disease. Recent studies showed that currently established disease genes differ in their protein size, tissue specificity and the phylogenetic distribution of homologs. These characteristics can be explained by the fact that monogenic disease mutations must be sufficiently deleterious to produce a clearly recognizable pheno Read More

Dissecting the genetic basis of complex diseases remains one of great challenges in human genetics, because these diseases have polygenic determinations and involve multiple gene-gene and gene-environmental interactions. Definite conclusions about finding genes underlying complex diseases need substantial evidence from three levels of gene function. The traditional strategy of gene identification is to determine put Read More

Unstable expansions of trinucleotide repeats (TNRs) are associated with a growing number of neurological disorders (at least 14), including HD (Huntington's disease), fragile X-syndrome, MD (Myotonic dystrophy) and Freidreich's ataxia. These disorders are often characterized by a tendency of certain pathological alleles to further expand due to biases in the parental origin of mutations, at times, leading to the most severe fo Read More