Reviews & Analysis

The availability of new genome sequence data and sophisticated analysis methods are enriching our understanding of human demographic history. The emerging model is more complex than the single origin hypothesis, and instead invokes a degree of gene flow between subpopulations.

Because of the complex phenotypes that are involved, the genetic basis of mate choice is particularly hard to unravel. Approaches that integrate classical quantitative genetics with modern genomic approaches promise to accelerate progress in this area.

If most evolutionary changes affect the regulation rather than the structure of proteins, then studying the evolution of gene expression levels will help us to understand phenotypic changes. How can this approach identify the defining differences between humans and chimpanzees?

The increase in population genetics data has led to a parallel need for sophisticated analysis programs and packages. This article is intended as a guide to many of these statistical programs, to promote their more informed use.

Recent advances from a range of systems have led to a rethink of how insulators prevent inappropriate interactions between neighbouring chromatin domains. The results suggest that, rather than having novel modes of action, insulators use adaptations of known regulatory mechanisms.

Artificial evolution implements the rules of natural evolution in algorithms that aim to solve biological and computational problems. The authors propose a new discipline, computational evolution, that replaces the outdated principles of artificial evolution with a modern understanding of biology.

Although genetics flourished in the first half of the twentieth century, human cytogenetics lagged behind, held up by the obstinate belief that humans had 48 chromosomes. This article examines the technical and psychological factors that hampered progress in the field.

Phosphatidylinositol 3-kinases (PI3Ks) are members of a unique and conserved family of intracellular lipid kinases that regulate a wide range of biological functions. Our understanding of the intricate regulation of this pathway is being applied to identify therapeutic strategies for diabetes and cancer.

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.