Representing the human genome as a sequence of bases or genes does not capture its higher level organization. But stepping back from the sequence can reveal a complex terrain with undulating patterns of sequence and structure — patterns that reflect differences such as base composition and chromosome banding. For one region in the genome, Eisenbarth et al. have found an association between base composition and linkage disequilibrium (LD) — an observation that has important implications for mapping the genes that underlie disease.

When two loci are close together, recombination between them is rare. Alleles at the two loci tend to occur together in a population more frequently than would be expected if they segregated randomly. The loci are said to be in LD and this provides a means to scan the genome for disease-susceptibility genes — if sufficient markers are used, it should be possible to detect LD between a marker and a candidate disease gene, and then home in on the gene itself. But recombination rates (and therefore LD) vary across the genome, so how do you know how many markers to use?

The neurofibromatosis gene, NF1 , is in a region of the human genome with variable LD and lies at the junction of two isochores — stretches of the genome associated with different levels of G+C content. Eisenbarth et al. show that the isochore junction coincides with a sharp transition in LD — high G+C is associated with low LD. From the degree of LD, they estimate that recombination rates on either side of the junction vary by around 100-fold, and each of the two regions extends for several hundred kilobases.

If this observation is repeated for other parts of the genome, G+C content could help to predict levels of LD. This will not only inform strategies to screen for LD in the genome, but will also provide an indication of the size of the region that needs to be searched once LD is identified. So, before you embark on an expedition to find genes associated with a particular disease, it could pay to know your genomic terrain.