Several studies have suggested a maternal excess in the transmission of type 2 (non-insulin-dependent) diabetes. However, the majority of these reports rely on patients recalling parental disease status and hence are open to criticism. An alternative approach is to study mitochondrial DNA (mtDNA) lineages. The hypervariable region 1 of the rapidly evolving noncoding section of mtDNA is suitable for investigating maternal ancestry and has been used extensively to study the origins of human racial groups. We have sequenced this 347-bp section of mtDNA from leukocytes of subjects with type 2 diabetes (n = 63) and age- and race-matched nondiabetic control subjects (n = 57). Consensus sequences for the two study groups were identical. Pairwise sequence analysis showed unimodal distribution of pairwise differences for both groups, suggesting that both populations had undergone expansion in ancient times. The distributions were significantly different (chi2 = 180, df = 11, P < 0.001); mean pairwise differences were 4.7 and 3.8 for the diabetic and control subjects, respectively. These data suggest that the diabetic subjects belong to an ancient maternal lineage that expanded before the major expansion observed in the nondiabetic population. Phylogenetic trees constructed using maximum parsimony, neighbor-joining, Fitch-Margolish, or maximum likelihood methods failed to show the clustering of all (or a subset) of the diabetic subjects into one or more distinct lineages.
Phylogenetic analysis of mitochondrial DNA in type 2 diabetes: maternal history and ancient population expansion.
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E J Sherratt, A W Thomas, R Gill-Randall, J C Alcolado; Phylogenetic analysis of mitochondrial DNA in type 2 diabetes: maternal history and ancient population expansion.. Diabetes 1 March 1999; 48 (3): 628–634. https://doi.org/10.2337/diabetes.48.3.628
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