Review Articles in 2006

Despite the key role of recombination in meiosis, increasing evidence indicates substantial variation in recombination rates among humans, and between humans and other mammals. Understanding the forces that shape this variation will require a combination of evolutionary and molecular perspectives.

Both genetic and physiological studies are contributing to our understanding of insect body size, a trait that affects fitness in many ways and is therefore subject to intense selection. Many of the genes that determine body size in insects have similar roles in mammals.

Intense investigation of the laminopathies has revised the traditional structural view of the nuclear lamina, highlighting crucial roles in processes including gene regulation and differentiation. This research has also led to a range of promising therapies for these rare diseases.

DNA signature tags, also known as molecular barcodes, were first developed in bacteria to facilitate functional screens by identifying mutants in mixed populations. Adaptations and refinements of this technology have yielded a wealth of information on a broad range of biological processes.

Combined with advances in immunology, genetic studies in human populations are revealing the diverse alterations in adaptive immunity that underlie autoimmune diseases. Recent studies have also highlighted an unexpected contribution of the innate immune system to these complex diseases.

Studies of regenerative biology have been hampered by a lack of tools for testing gene function in traditional model species. Recent advances have overcome this problem, leading to new insights into both basic regenerative biology and its biomedical potential.

The recently emerged field of genetic analysis of global gene expression has shed light on the architecture of quantitative traits, transcriptional regulation and regulatory variation. It has provided a way of connecting DNA sequence variation with phenotypic variation.

The sonic hedgehog signalling molecule controls development at many stages and by different mechanisms. This article uses it to exemplify the fundamental mechanisms by which developmental growth and patterning are regulated in both vertebrates and invertebrates.

Complex physiological inputs and environmental influences have made mapping genetic determinants of hypertension susceptibility particularly challenging. Refining results from previous studies in both rats and humans, combined with new genome-wide approaches, is set to accelerate progress in this area.

Genomic techniques have pervaded studies of speciation genetics. Although they might not have led to changes in the prevailing hypotheses, the accelerated pace of data collection and compilation should help us to understand the relative frequency and importance of the different processes that cause speciation.

The concept of relatedness is central to many fields, from human linkage analysis to forensics to animal and plant breeding. This review covers the statistical framework for studying relatedness, its applications and the challenges that the field faces.

Identifying polymorphisms that are overrepresented in disease cases versus controls would seem to be a straightforward process, but genetic association studies are notoriously riddled with complex analysis problems. This article outlines these statistical issues and provides some guidance to overcoming them.

Several models have been proposed to explain the spreading of heterochromatin, including looping, sliding and oozing. A review of studies from diverse model eukaryotes allows the authors to evaluate the existing models and leads them to propose a common, ancestral mechanism for spreading.

The vast increase in the amount of molecular genetic data that are being generated, and the scale of their complexity, demand ever more sophisticated statistical analysis methods — this article surveys and compares these approaches, and the growing reliance on computational methodologies.

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.

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.