January 25, 2005

Linkage disequilibrium varies among populations

Linkage disequilibrium (LD) is said to occur when knowledge of the allele in a particular locus (gene) gives us information about the state of the allele in a different locus. That is, in a sense, these two genes are co-inherited, and this is often the case when genes are very close to each other on a chromosome (and thus the probability of them being split during meiosis is limited), or when they "work well together", making their co-occurrence more likely.

A new paper in European Journal of Human Genetics studies the extent to which LD varies among different human populations. This is an important finding since LD is often used to determine how many polymorphisms to examine. For example, if a long sequence of DNA is in LD, then typing a single SNP somewhere on it implicitly reveals the state of the entire sequence. But this may lead to mistakes if applied to a different population X for which whole sequence information is not available, as the sequence in question might not be in LD in X.

The paper confirms the lower LD in Africans than in non-Africans, which may be used to support an African origin for humans. However, an important finding is that LD is not the same in different loci, with e.g., Europeans showing higher LD in a particular locus than Asians and vice versa.

European Journal of Human Genetics (advance online publication)

Linkage disequilibrium patterns vary substantially among populations

Sarah L Sawyer et al.

A major initiative to create a global human haplotype map has recently been launched as a tool to improve the efficiency of disease gene mapping. The 'HapMap' project will study common variants in depth in four (and to a lesser degree in up to 12) populations to catalogue haplotypes that are expected to be common to all populations. A hope of the 'HapMap' project is that much of the genome occurs in regions of limited diversity such that only a few of the SNPs in each region will capture the diversity and be relevant around the world. In order to explore the implications of studying only a limited number of populations, we have analyzed linkage disequilibrium (LD) patterns of three 175-320 kb genomic regions in 16 diverse populations with an emphasis on African and European populations. Analyses of these three genomic regions provide empiric demonstration of marked differences in frequencies of the same few haplotypes, resulting in differences in the amount of LD and very different sets of haplotype frequencies. These results highlight the distinction between the statistical concept of LD and the biological reality of haplotypes and their frequencies. The significant quantitative and qualitative variation in LD among populations, even for populations within a geographic region, emphasizes the importance of studying diverse populations in the HapMap project to assure broad applicability of the results.


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