Evidence of non-random mutation rates suggests an evolutionary risk management strategy

• May 3rd, 2012

Martincorena et al are reporting in Nature evidence challenging the tenet that mutations occur randomly and then selection governs whether they are fixed or not. By comparing 34 E.coli genomes  and after excluding usual causes of difference in mutation rate (codon usage bias, mRNA-folding stability in the 5´, GC content and within-species homologous recombination)  the authors observe that the neutral mutation rate varies by more than an order of magnitude across 2.659 genes. The mutation rate is lower at highly expressed genes implying the presence of unknown compensatory mechanisms. They go a step further showing that purifying, rather than positive, selection has driven the evolution of the local point mutation rate in order to reduce risk of deleterious mutations and possibly increase the rate of non-deleterious mutations thus increasing the adaptive potential.

Periklis Makrythanasis, MD, PhD

Martincorena I, Seshasayee AS, Luscombe NM.; Nature. 2012 Apr 22. doi: 10.1038/nature10995. [Epub ahead of print]

OMMBID Chapter 13: The Nature and Mechanisms of Human Gene Mutation

Metabolomics for IEMs

• March 24th, 2008

Clin Chem. 2007 Dec;53(12):2169-76. Epub 2007 Oct 19.
Metabolomics identifies perturbations in human disorders of propionate metabolism.
Wikoff WR, Gangoiti JA, Barshop BA, Siuzdak G.
In this publications, the authors use mass-based metabolomics to identify compounds which differ from normal individuals in the plasma of patients with methylmalonic aciduria and propionic aciduria.
Not surprinsingly, propionylcarnitine was the best marker for the disease. New compounds such as gamma-butyrobetaine (possibly related to carnitine supplementation) and other unidentified compounds were detected.

This demonstrates the potential usefulness of metabolomics in inborn errors of metabolism, to identify new markers of the disease (e.g. to follow treatment). Eventually, if the process is optimized to allow rapid screening of samples, it might become possible to identify new IEMs using such metabolomic approaches.

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Click this link to see the most recent online abstracts of major genetics journals.
Philippe Campeau, MD
Resident in Medical Genetics at McGill University
OMMBID Blog Administrator

The human disease network

• July 20th, 2007

Combining the efforts of great minds in the field of network science and medical genetics, this paper describes the diseasome, an integrated network of genetic disorders.

See figure 13 for a great overview of some allelic conditions.

Goh KI, Cusick ME, Valle D, Childs B, Vidal M, Barabasi AL.
The human disease network.
Proc Natl Acad Sci U S A. 2007 May 22;104(21):8685-90

Thank you very much in advance for your contributions to this blog (Click on login to register and post a comment).

Click this link to see the most recent online abstracts of major genetics.

Philippe Campeau, MD
Resident in Medical Genetics at McGill University
OMMBID Blog Administrator

24 genetic risk factors for 7 common human diseases

• June 6th, 2007

See this link for a very interesting discussion and paper in Nature.
Sincerely,
Philippe Campeau

Human Variome Project

• March 31st, 2007

 
The Human Variome Project participants have met in 2006 and have established 96 recommendations for the collection and accessibility of variations in the human genomic DNA.

Nat Genet. 2007 Apr;39(4):433-6.

Recommendations of the 2006 Human Variome Project meeting.

Cotton RG; participants of the 2006 Human Variome Project meeting; Appelbe W,
Auerbach AD, Becker K, Bodmer W, Boone DJ, Boulyjenkov V, Brahmachari S, Brody
L, Brookes A, Brown AF, Byers P, Maria Cantu J, Cassiman JJ, Claustres M,
Concannon P, Cotton RG, den Dunnen JT, Flicek P, Gibbs R, Hall J, Hasler J, Katz
M, Kwok PY, Laradi S, Lindblom A, Maglott D, Marsh S, Masimirembwa CM, Minoshima
S, de Ramirez AM, Pagon R, Ramesar R, Ravine D, Richards S, Rimoin D, Ring HZ,
Scriver CR, Sherry S, Shimizu N, Stein L, Tadmouri GO, Taylor G, Watson M.

Richard G.H. Cotton is at the Genomic Disorders Research Centre, St. Vincent’s
Hospital Melbourne, 35 Victoria Parade, Melbourne, Victoria 3065, Australia. The
complete list of the authors appears at the end of the paper*.

Human Variome Project

• March 31st, 2007

 
The Human Variome Project participants have met in 2006 and have established 96 recommendations for the collection and accessibility of variations in the human genomic DNA.

Nat Genet. 2007 Apr;39(4):433-6.

Recommendations of the 2006 Human Variome Project meeting.

Cotton RG; participants of the 2006 Human Variome Project meeting; Appelbe W,
Auerbach AD, Becker K, Bodmer W, Boone DJ, Boulyjenkov V, Brahmachari S, Brody
L, Brookes A, Brown AF, Byers P, Maria Cantu J, Cassiman JJ, Claustres M,
Concannon P, Cotton RG, den Dunnen JT, Flicek P, Gibbs R, Hall J, Hasler J, Katz
M, Kwok PY, Laradi S, Lindblom A, Maglott D, Marsh S, Masimirembwa CM, Minoshima
S, de Ramirez AM, Pagon R, Ramesar R, Ravine D, Richards S, Rimoin D, Ring HZ,
Scriver CR, Sherry S, Shimizu N, Stein L, Tadmouri GO, Taylor G, Watson M.

Richard G.H. Cotton is at the Genomic Disorders Research Centre, St. Vincent’s
Hospital Melbourne, 35 Victoria Parade, Melbourne, Victoria 3065, Australia. The
complete list of the authors appears at the end of the paper*.

Historical perspectives in genetics

• December 28th, 2006

For interesting perspectives on the history of genetics, please refer to these websites, books and papers:

Electronic Scholarly Publishing, started by Robert J Robbins.

Nature Reviews in Genetics series on Historical Profiles and the History of genetic diseases.

Landmarks in Medical Genetics
Classic Papers with Commentaries
Edited by Peter S. Harper
ISBN 13: 9780195159301
ISBN 10: 0195159306
336 pages, 2004 

The Journal of the History of Medicine and Allied Ressources 

OMMBID Chapter 3 : The Inborn Error and Biochemical Individuality
Authors: Barton Childs, David Valle, Gerardo Jimenez-Sanchez

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Philippe Campeau, MD
Resident in Medical Genetics at McGill University
OMMBID Blog Administrator

Drugs for rare conditions

• December 25th, 2006

J Intern Med. 2006 Jul;260(1):1-10.

Wastfelt M, Fadeel B, Henter JI.

This article gives interesting insights on the development of orphan drugs for rare disorders. It also contains a list of great websites.

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Philippe Campeau, MD
Resident in Medical Genetics at McGill University
OMMBID Blog Administrator

Liver transplantation for inborn errors of metabolism

• October 23rd, 2006

This articles provides an overview and discussion on an important area of the treatment of inborn errors of metabolism.
Transplantation. 2005 Sep 27;80(1 Suppl):S135-7.

Liver transplantation for inborn errors of metabolism.

Meyburg J, Hoffmann GF.

Genetic Modification Clinical Research Information System

• July 24th, 2006

GeMCRIS, a NIH initiative, is a comprehensive database of human gene therapy trials. It is easily searchable and very reliable.

Thank you very much in advance for your contributions to this blog (Click on login to register and post a message).

Philippe Campeau, MD
Resident in Medical Genetics at McGill University
OMMBID Blog Administrator