Review Articles in 2006

The sex chromosomes of mammals andDrosophilaspecies are broadly similar, including in the forces that have shaped their independent evolution. Studying the basis of their differences, however, is informing our understanding of several population-genetic processes beyond eukaryotic-genome evolution.

Given the volume, complexity and heterogeneity of data generated by high-throughput approaches, modern biology needs standards for data representation and communication. But how should such standards be developed? What types of standard are needed and what determines whether they are successfully adopted by the community?

Fifteen years after the first generation of microarray platforms for highly parallel genomic analysis, intrinsically parallel whole-genome approaches to genotyping, epigenetic profiling and sequencing are being developed. What are the recent key developments that promise to transform the study of human health and disease?

In mammals, the SRY protein initiates the male developmental programme. This begins with testis determination and is followed by a network of transcriptional and endocrine signalling events in other organs. The authors review our current understanding of this process.

Genotypes act not only on individuals but on entire ecological communities. Although it is a complex undertaking, it is possible to extend population and quantitative genetics principles to understanding ecosystem processes, and place them in an evolutionary framework.

Segmental duplications are emerging as key contributors to the evolution of primate genomes. Furthermore, determining how, and when, these duplications arose and diversified is proving to be an essential goal in understanding human phenotypic variation and disease susceptibility.

The sequence, structure and folding properties of DNA are being exploited in innovative ways, thereby expanding the uses of DNA beyond its natural calling. This article examines those applications, which range from disease diagnostics to molecular computing.

High-throughput genomics data have provided a genome-wide picture of alternative splicing in multiple organisms. Genome sequencing and comparative genomics have revealed the evolutionary impact of alternative splicing and the constraints on evolution associated with the regulation of alternative splicing.

With its genome sequenced,Arabidopsis thaliana— one of the main genetic model organisms — has moved into the functional genomic era. Classical forward genetic approaches are now being combined with reverse genetics to analyse the complete plant phenome — gene function on the genome scale.

A growing number of diseases are known to result from genetic defects in glycosylation pathways. Recent studies have begun to reveal the diverse ways in which glycosylation defects can cause disease, and the many functions of the glycome.

Inborn errors of metabolism (IEM) are often thought of as Mendelian, but are in fact good examples of multifactorial traits. Advances in IEM diagnosis and management lie in combining dynamic measurements of metabolic flux with a range of omics data.

Mutations that affect the MECP2 protein, which binds methylated DNA, cause the neurodevelopmental disorder Rett syndrome. Exciting advances are being made in understanding how MECP2 defects affect the interpretation of DNA methylation marks to cause specific disease phenotypes.

Increasing evidence indicates that ATP-dependent chromatin remodelling has specific and tightly controlled functions in the regulation of gene expression during mammalian differentiation. Recent studies also link chromatin-remodelling activities to other key events in the differentiation process.

Although an abundance of candidate genes have been highlighted as possible determinants of human longevity, only one finding has been replicated. Larger and longer-running studies, careful consideration of study design, and improved analyses hold the key to future progress.

Effective gene drive systems for spreading genes that can block the transmission of insect-borne pathogens are much needed. Naturally occurring selfish genetic elements have enormous potential that can be exploited to control of some of the world's most devastating diseases.

Many factors other than protein structure and function affect the rate of protein evolution. Advances in genomics make it possible to assess the contribution of all these factors and move towards a more integrated view of how proteins evolve.

Although major molecular players with a role in mesoderm induction have been identified, high-throughput approaches are beginning to yield data that will help us to understand how the embryo integrates and processes the various signals during mesoderm induction.

Although they are sometimes overlooked, family-based designs provide important advantages for detecting genetic associations in studies of complex disease. In particular, they provide a means of overcoming the problems that arise when multiple hypotheses are tested in genome-wide association studies.

Stem-cell systems all raise similar kinds of issues concerning the nature of the niche and the differentiation process. Genetic studies of the intestinal stem-cell system have made strides in providing generally applicable answers to such questions.

Carrying out high-throughput, cell-based RNA interference screens involves making a range of decisions, from choosing the cell type and reagents to picking strategies for optimization and validation. Informed planning at each stage allows the power of this approach to be maximized.