Articles

Novel variants of major drug-metabolising enzyme genes in diverse African populations and their predicted functional effects

Pharmacogenetics enables personalised therapy based on genetic profiling and is increasingly applied in drug discovery. Medicines are developed and used together with pharmacodiagnostic tools to achieve desire...

Authors: Alice Matimba, Jurgen Del-Favero, Christine Van Broeckhoven and Collen Masimirembwa

LIPEC-60G influences the effects of physical activity on body fat and plasma lipid concentrations: the Quebec Family Study

A large body of evidence suggests that the environment plays an important role in the development of obesity. The hormone-sensitive lipase (encoded by the LIPE gene) is an intracellular enzyme that mobilises fat ...

Authors: Christophe Garenc, Marie-Claude Vohl, Claude Bouchard and Louis Pérusse

Whole-genome approach implicates CD44in cellular resistance to carboplatin

Carboplatin is a chemotherapeutic agent used in the management of many cancers, yet treatment is limited by resistance and toxicities. To achieve a better understanding of the genetic contribution to carboplat...

Authors: Sunita J. Shukla, Shiwei Duan, Xiaolin Wu, Judith A. Badner, Kristen Kasza and M. Eileen Dolan

Biosimulation in Drug Development: Martin Bertau, Erik Mosekilde, Hans V. Westerhoff

Authors: Michael PH Stumpf

Update on the olfactory receptor (OR) gene superfamily

The olfactory receptor gene (OR) superfamily is the largest in the human genome. The superfamily contains 390 putatively functional genes and 465 pseudogenes arranged into 18 gene families and 300 subfamilies. Ev...

Authors: Tsviya Olender, Doron Lancet and Daniel W. Nebert

A survey of genetic simulation software for population and epidemiological studies

A number of programs have been developed for simulating population genetic and genetic epidemiological data conforming to one of three main algorithmic approaches: 'forwards', 'backwards' and 'sideways'. This ...

Authors: Youfang Liu, Georgios Athanasiadis and Michael E. Weale

Mitochondrial DNA sequence variation and neurodegeneration

Mitochondria, the powerhouse of the cell, play a critical role in several metabolic processes and apoptotic pathways. Many lines of evidence suggest that mitochondria have a central role in ageing-related neur...

Authors: Michelangelo Mancuso, Massimiliano Filosto, Daniele Orsucci and Gabriele Siciliano

Genome-wide identification of genetic determinants for the cytotoxicity of perifosine

Perifosine belongs to the class of alkylphospholipid analogues, which act primarily at the cell membrane, thereby targeting signal transduction pathways. In phase I/II clinical trials, perifosine has induced t...

Authors: Wei Zhang, Wanqing Liu, Enrique Poradosu and Mark J. Ratain

Hardy-Weinberg analysis of a large set of published association studies reveals genotyping error and a deficit of heterozygotes across multiple loci

In genetic association studies, deviation from Hardy-Weinberg equilibrium (HWD) can be due to recent admixture or selection at a locus, but is most commonly due to genotyping errors. In addition to its utility...

Authors: Srijan Sen and Margit Burmeister

The role of aldehyde dehydrogenase-1 (ALDH1A1) polymorphisms in harmful alcohol consumption in a Finnish population

Liver cystolic aldehyde dehydrogenase 1 (ALDH1A1) has been previously associated with both alcohol dependence and alcohol consumption behaviour, and has been implicated in alcohol-induced flushing and alcohol ...

Authors: Penelope A. Lind, C. J. Peter Eriksson and Kirk C. Wilhelmsen

A high incidence of polymorphic CYP2C19variants in archival blood samples from Papua New Guinea

There is considerable inter-ethnic variability in the incidence of CYP2C19 genetic poor metabolisers (var/var). About 3 per cent of Caucasians are CYP2C19 var/var. By contrast, an extremely high incidence (70 per...

Authors: Huai-Ling Hsu, Kathryn J. Woad, D. Graeme Woodfield and Nuala A. Helsby

Influence of SLCO1B1 and CYP2C8gene polymorphisms on rosiglitazone pharmacokinetics in healthy volunteers

Polymorphisms in drug transporter genes and/or drug-metabolising enzyme genes may contribute to inter-individual variability in rosiglitazone pharmacokinetics in humans. We sought to determine the joint effect...

Authors: Christina L Aquilante, Lane R. Bushman, Shannon D. Knutsen, Lauren E. Burt, Lucille Capo Rome and Lisa A. Kosmiski

Guest Editorial

Authors: Allan C Collins, Matthew McQueen and Marissa Ehringer

Editorial

Authors: Vasilis Vasiliou

Bioinformatics methods for identifying candidate disease genes

With the explosion in genomic and functional genomics information, methods for disease gene identification are rapidly evolving. Databases are now essential to the process of selecting candidate disease genes....

Authors: Marc A van Driel and Han G Brunner

Genome-wide approaches to understanding human ageing

The use of genomic technologies in biogerontology has the potential to greatly enhance our understanding of human ageing. High-throughput screens for alleles correlated with survival in long-lived people have ...

Authors: Matt Kaeberlein

Genetic association studies in cancer: Good, bad or no longer ugly?

For some time, investigators have appreciated that genetic association studies in cancer are complex because of the multi-stage process of cancer and the daunting challenge of analysing genetic variants in pop...

Authors: Sharon A Savage and Stephen J Chanock

Strategies for the detection of copy number and other structural variants in the human genome

Advances in genome scanning technologies are revealing that copy number variants (CNVs) and polymorphisms, ranging from a few kilobases to several megabases in size, are present in genomes at frequencies much ...

Authors: Andrew R Carson, Lars Feuk, Mansoor Mohammed and Stephen W Scherer

Functional single nucleotide polymorphism-based association studies

Association studies hold great promise for the elucidation of the genetic basis of diseases. Studies based on functional single nucleotide polymorphisms (SNPs) or on linkage disequilibrium (LD) represent two m...

Authors: Victoria EH Carlton, James S Ireland, Francisco Useche and Malek Faham

From DNA to RNA to disease and back: The 'central dogma' of regulatory disease variation

Much of the focus of human disease genetics is directed towards identifying nucleotide variants that contribute to disease phenotypes. This is a complex problem, often involving contributions from multiple loc...

Authors: Barbara E. Stranger and Emmanouil T. Dermitzakis

Stepwise haplotype analysis: Are LD patterns repeatable?

A variety of techniques exist to describe and depict patterns of pairwise linkage disequilibrium (LD). In the current paper, a new log-linear framework is proposed for the summarisation of local interactions a...

Authors: A. P. Mander and A. Bansal

Genetic factors leading to chronic Epstein-Barr virus infection and nasopharyngeal carcinoma in South East China: Study design, methods and feasibility

Nasopharyngeal carcinoma (NPC) is a complex disease caused by a combination of Epstein-Barr virus chronic infection, the environment and host genes in a multi-step process of carcinogenesis. The identity of ge...

Authors: Xiu Chan Guo, Kevin Scott, Yan Liu, Michael Dean, Victor David, George W. Nelson, Randall C. Johnson, Holli H. Dilks, James Lautenberger, Bailey Kessing, Janice Martenson, Li Guan, Shan Sun, Hong Deng, Yuming Zheng, Guy de The…

A non-parametric approach to population structure inference using multilocus genotypes

Inference of population structure from genetic markers is helpful in diverse situations, such as association and evolutionary studies. In this paper, we describe a two-stage strategy in inferring population st...

Authors: Nianjun Liu and Hongyu Zhao

Testing groups of genomic locations for enrichment in disease loci using linkage scan data: A method for hypothesis testing

Genes for complex disorders have proven hard to find using linkage analysis. The results rarely reach the desired level of significance and researchers often have failed to replicate positive findings. There i...

Authors: Dimitrios Avramopoulos, Peter Zandi, Adrian Gherman, M. Daniele Fallin and Susan S. Bassett

Letter to the Editor

Authors: Göran Levan and Howard J. Jacob

Genome-wide association studies getting more complicated but help is on the way

Authors: Pui-Yan Kwok

A survey of data mining methods for linkage disequilibrium mapping

Data mining methods are gaining more interest as potential tools in mapping and identification of complex disease loci. The methods are well suited to large numbers of genetic marker loci produced by high-thro...

Authors: Päivi Onkamo and Hannu Toivonen

Update of the NAD(P)H:quinone oxidoreductase (NQO) gene family

The NAD(P)H:quinone acceptor oxidoreductase (NQO) gene family belongs to the flavoprotein clan and, in the human genome, consists of two genes (NQO1 and NQO2). These two genes encode cytosolic flavoenzymes that c...

Authors: Vasilis Vasiliou, David Ross and Daniel W. Nebert

Multifactor dimensionality reduction: An analysis strategy for modelling and detecting gene - gene interactions in human genetics and pharmacogenomics studies

The detection of gene - gene and gene - environment interactions associated with complex human disease or pharmacogenomic endpoints is a difficult challenge for human geneticists. Unlike rare, Mendelian diseas...

Authors: Alison A Motsinger and Marylyn D Ritchie

Detecting multiple associations in genome-wide studies

Recent developments in the statistical analysis of genome-wide studies are reviewed. Genome-wide analyses are becoming increasingly common in areas such as scans for disease-associated markers and gene express...

Authors: Frank Dudbridge, Arief Gusnanto and Bobby PC Koeleman

Fabry disease: Identification of 50 novel α-galactosidase A mutations causing the classic phenotype and three-dimensional structural analysis of 29 missense mutations

Fabry disease, an X-linked recessive inborn error of glycosphingolipid catabolism, results from the deficient activity of the lysosomal exoglycohydrolase, α-galactosidase A (EC 3.2.1.22; α-Gal A). The molecula...

Authors: Junaid Shabbeer, Makiko Yasuda, Stacy D Benson and Robert J Desnick

Functional nsSNPs from carcinogenesis-related genes expressed in breast tissue: Potential breast cancer risk alleles and their distribution across human populations

Although highly penetrant alleles of BRCA1 and BRCA2 have been shown to predispose to breast cancer, the majority of breast cancer cases are assumed to result from the presence of low-moderate penetrant alleles a...

Authors: Sevtap Savas, Steffen Schmidt, Hamdi Jarjanazi and Hilmi Ozcelik

Human SNPs resulting in premature stop codons and protein truncation

Single nucleotide polymorphisms (SNPs) constitute the most common type of genetic variation in humans. SNPs introducing premature termination codons (PTCs), herein called X-SNPs, can alter the stability and fu...

Authors: Sevtap Savas, Sukru Tuzmen and Hilmi Ozcelik

Letter to the Editor

Authors: David R Nelson

Editorial

Authors: Li Jin

Comparison of human (and other) genome browsers

The sequence of the human genome provides a scaffold on which numerous annotations, such the locations of genes, can be laid. Genome browsers have been created to allow the simultaneous display of multiple ann...

Authors: Terrence S Furey

Integrated analysis of genetic data with R

Genetic data are now widely available. There is, however, an apparent lack of concerted effort to produce software systems for statistical analysis of genetic data compared with other fields of statistics. It ...

Authors: Jing Hua Zhao and Qihua Tan

Mitochondrial DNA as a potential tool for early cancer detection

The recent surge in mitochondrial research has been driven by the identification of mitochondria-associated diseases and the role of mitochondria in apoptosis. Both of these aspects have identified mitochondri...

Authors: Ryan L Parr, Gabriel D Dakubo, Robert E Thayer, Keith McKenney and Mark A Birch-Machin

Immunogenomics: Molecular hide and seek

Similar to other classical science disciplines, immunology has been embracing novel technologies and approaches giving rise to specialised sub-disciplines such as immunogenetics and, more recently, immunogenom...

Authors: Marcos M Miretti and Stephan Beck

FDA perspectives on potential microarray-based clinical diagnostics

The US Food and Drug Administration (FDA) encourages the development of new technologies such as microarrays which may improve and streamline assessments of safety and the effectiveness of medical products for...

Authors: Živana Težak, Daya Ranamukhaarachchi, Estelle Russek-Cohen and Steven I Gutman

Inference of ancestry: constructing hierarchical reference populations and assigning unknown individuals

The ability to infer personal genetic ancestry is being increasingly utilised in certain medical and forensic situations. Herein, the unsupervised Bayesian clustering algorithms structure, is employed to analyse ...

Authors: Jayne E Ekins, Jacob B Ekins, Lara Layton, Luke AD Hutchison, Natalie M Myres and Scott R Woodward

Genomic analysis of a heterogeneous Mendelian phenotype: multiple novel alleles for inherited hearing loss in the Palestinian population

Recessively inherited phenotypes are frequent in the Palestinian population, as the result of a historical tradition of marriages within extended kindreds, particularly in isolated villages. In order to charac...

Authors: Tom Walsh, Amal Abu Rayan, Judeh Abu Sa'ed, Hashem Shahin, Jeanne Shepshelovich, Ming K Lee, Koret Hirschberg, Mustafa Tekin, Wa'el Salhab, Karen B Avraham, Mary-Claire King and Moien Kanaan

Editorial

Authors: Li Jin

Gene nomenclature by default, or BLASTing to Babel

The current proliferation of mammalian genomes is creating a nomenclature issue caused by naming genes based on their best BLAST hit to a gene in another annotated genome. The rat genome is relying heavily on ...

Authors: David R. Nelson

Software for quantitative trait analysis

This paper provides a brief overview of software currently available for the genetic analysis of quantitative traits in humans. Programs that implement variance components, Markov Chain Monte Carlo (MCMC), Has...

Authors: Laura Almasy and Diane M Warren

Web-based resources for comparative genomics

The available web-based genome data and related resources provide great opportunities for biomedical scientists to identify functional elements in a particular genome region or to explore the evolutionary patt...

Authors: Xun Gu and Zhixi Su

How homologous recombination generates a mutable genome

Recombination and mutation have traditionally been regarded as independent evolutionary processes: the latter generates variation, which the former reshuffles. Recent studies, however, have suggested that alle...

Authors: Matthew Hurles

Functional constraints on the constitutive androstane receptor inferred from human sequence variation and cross-species comparisons

Members of the NR1I subfamily of nuclear receptors play a role in the transcriptional activation of genes involved in drug metabolism and transport. NR1I3, the constitutive androstane receptor (CAR), mediates ...

Authors: Emma E Thompson, Hala Kuttab-Boulos, Matthew D Krasowski and Anna Di Rienzo

Divergence, recombination and retention of functionality during protein evolution

We have only a vague idea of precisely how protein sequences evolve in the context of protein structure and function. This is primarily because structural and functional contexts are not easily predictable fro...

Authors: Yanlong O Xu, Randall W Hall, Richard A Goldstein and David D Pollock

Editorial

Authors: Laurent Excoffier