|
| ||
|
|
||
Biological Insight (biological + insight)
Selected AbstractsAnalysis of genotype,phenotype correlations in human holoprosencephaly,,AMERICAN JOURNAL OF MEDICAL GENETICS, Issue 1 2010Benjamin D. Solomon§ Abstract Since the discovery of the first gene causing holoprosencephaly (HPE), over 500 patients with mutations in genes associated with non-chromosomal, non-syndromic HPE have been described, with detailed descriptions available in over 300. Comprehensive clinical analysis of these individuals allows examination for the presence of genotype,phenotype correlations. These correlations allow a degree of differentiation between patients with mutations in different HPE-associated genes and for the application of functional studies to determine intragenic correlations. These early correlations are an important advance in the understanding of the clinical aspects of this disease, and in general argue for continued analysis of the genetic and clinical findings of large cohorts of patients with rare diseases in order to better inform both basic biological insight and care and counseling for affected patients and families. Published 2010 Wiley-Liss, Inc. [source] Using the protein chip interface with quadrupole time-of-flight mass spectrometry to directly identify peaks in SELDI profiles , initial evaluation using low molecular weight serum peaksPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 2 2009Jianhe Peng Abstract Mass spectrometric profiling, particularly in the form of SELDI, has been used in many studies, particularly in attempts to generate diagnostic serum profiles. Several studies have generated promising results but one of the limitations is the inability to identify easily potential discriminatory peaks. This may enable specific assays to be developed and increased biological insight. We describe the first systematic technical evaluation of the ProteinChip interface coupled to a tandem mass spectrometer which allows direct sequencing of peptides <6000,Da, and describe the direct sequence identification of 21 peaks commonly observed in serum samples. Additionally we describe for the first time the use of on-chip acetylation to assist in the validation of sequence identification. [source] Advances in protein turnover analysis at the global level and biological insightsMASS SPECTROMETRY REVIEWS, Issue 5 2010Qingbo Li Abstract The concept of a dynamic state of body constituents, a precursor of the modern term of proteome dynamics, was conceived over a century ago. But, not until recently can we examine the dynamics of individual "constituents" for example, proteins at a truly global level. The path of advancement in our understanding of protein turnover at the global level is marked by the introduction of some key technological innovations. These methods include the isotopic tracer technique in the 1930s, the two-dimensional gel electrophoresis technique in the 1970s, the sector mass spectrometer that could analyze isotopomers of peptides in the early 1990s, the 2D gel/MALDI-TOF proteomics technology in the late 1990s, the booming liquid chromatography/mass spectrometry proteomics technology in this decade, and the recently emerging protein-tagging approaches that offer single-cell resolution for protein turnover measurements. The long-standing inquiry raised in the 1950s about the existence of a dynamic state in different organisms at different physiological conditions can now be answered with an individual "constituent" resolution on a truly global scale. Now it appears that protein degradation is not necessarily an end to the protein function. Rather, it can be the start of a new function because protein degradation clears the way for the action of other proteins. Protein turnover participates in a multi-layer complex regulatory network and shares equal importance with gene transcription and protein translation. The advances in technologies for protein turnover analysis and the improved understanding of the biological role of protein turnover will likely help to solve some long-standing biomedical problems such as the tuberculosis disease that at the present day still affects one-third of the world population. © 2009 Wiley Periodicals, Inc., Mass Spec Rev 29:717,736, 2010 [source] The molecular genetics of the genodermatoses: progress to date and future directionsBRITISH JOURNAL OF DERMATOLOGY, Issue 1 2003A.D. Irvine Summary The Human Genome Mapping Project and allied rapid advances in genetic technology over the past decade have facilitated accurate association of allelic variations in several genes with specific skin phenotypes. Currently the genetic bases of the majority of the more common genodermatoses have been elucidated. In scientific terms this work has been extraordinarily successful and has yielded many new biological insights. These advances, although exciting, have yet to be translated into direct benefit for patients with these diseases. Genetic counselling has been greatly aided by gene identification, by the better understanding of genotype,phenotype correlation and by the disclosure of unexpected genetic mechanisms in some families. Knowledge of the molecular basis of these disorders has also been vital in enabling DNA-based prenatal diagnosis in several conditions and DNA-based preimplantation diagnosis has been used in a selected few. While this successful period of gene mapping is now nearing completion, progress towards the next goal, that of developing therapeutic strategies based on the knowledge of these underlying genetic mechanisms, has proven frustratingly slow. Despite the ready access to the skin compared with solid internal organs, the challenges of cutaneous gene therapy are legion and many technical issues need to be surmounted to enable gene replacement or modification of gene expression to have a useful role in these disorders. In this article we make a comprehensive review of progress to date in gene identification, genotype,phenotype correlation, prenatal diagnosis and cutaneous gene therapy, and we examine future directions for research in this field. [source] | ||||||||||