Gene expression phenotypes linked to ethnicity

19 January 2007

The prevalence of some monogenic (Mendelian) diseases such as cystic fibrosis varies between populations, due to different frequencies of the mutant alleles within each population. Similarly, many complex diseases (with multiple genetic and environmental factors affecting disease susceptibility) also show varying prevalence between populations. For example, individuals from South Asian populations living in the UK have a greater than average prevalence of coronary heart disease, whilst those of Afro-Caribbean origin have a relatively high prevalence of hypertension. Similarly, Mexican Americans and American Indians have generally higher rates of type II diabetes than Americans of predominantly European origin. These differences are presumed to arise from differing allele frequencies for multiple polymorphisms that affect key genes involved in disease resistance and susceptibility.

A new study published in Nature Genetics uses microarray technology to analyse the expression of more than 4000 genes in white blood cells from Asian and Caucasian populations [Spielman RS et al. (2007) Nat Genet. Jan 7; Epub ahead of print]. The distinct characteristics of specialised cell types arise from the pattern of gene expression for that cell type – which genes are expressed, and at what level. More than 1000 of the genes analysed were found to show differential expression levels between the population groups. The researchers found that much of these differences were the result of sequence variation in the form of single nucleotide polymorphisms (SNPs) – but in the non-coding regulatory regions adjacent to the genes, rather than the coding regions of the genes themselves. They conclude that allele frequency differences at regulatory polymorphisms account for some of the observed differences between populations in the prevalence of complex diseases by causing variation in gene expression.

Comment: This work adds a new element to the undoubtedly complex genetic variation that affects the susceptibility of different population groups to various disease states, although firm conclusions cannot really be drawn from a study that looked at gene expression in only one cell type, from a limited number of different samples (142). The true in vivo situation with respect to gene expression could also differ from that in a laboratory maintained cell line.

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