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Open Access Highly Accessed Research article

Differences in mtDNA haplogroup distribution among 3 Jewish populations alter susceptibility to T2DM complications

Jeanette Feder1, Ilana Blech2, Ofer Ovadia1, Shirly Amar3, Julio Wainstein45, Itamar Raz46, Sarah Dadon1, Dan E Arking7, Benjamin Glaser24 and Dan Mishmar1*

Author Affiliations

1 Department of Life Sciences and National Institute of Biotechnology in the Negev (NIBN), Ben-Gurion University of the Negev, Beer-Sheva, Israel

2 Endocrinology and Metabolism Service, Internal Medicine Department, Hadassah-Hebrew University Medical Center, Jerusalem, Israel

3 Stanley Research Center, Ben-Gurion University of the Negev and Mental Health Center, Beer-Sheva, Israel

4 Israel Diabetes Research Group (IDRG), Israel

5 Wolfson Hospital, Holon, Israel

6 Diabetes Unit, Internal Medicine Department, Hadassah-Hebrew University Medical Center, Jerusalem, Israel

7 McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA

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BMC Genomics 2008, 9:198  doi:10.1186/1471-2164-9-198

Published: 29 April 2008



Recent genome-wide association studies searching for candidate susceptibility loci for common complex diseases such as type 2 diabetes mellitus (T2DM) and its common complications have uncovered novel disease-associated genes. Nevertheless these large-scale population screens often overlook the tremendous variation in the mitochondrial genome (mtDNA) and its involvement in complex disorders.


We have analyzed the mitochondrial DNA (mtDNA) genetic variability in Ashkenazi (Ash), Sephardic (Seph) and North African (NAF) Jewish populations (total n = 1179). Our analysis showed significant differences (p < 0.001) in the distribution of mtDNA genetic backgrounds (haplogroups) among the studied populations. To test whether these differences alter the pattern of disease susceptibility, we have screened our three Jewish populations for an association of mtDNA genetic haplogroups with T2DM complications. Our results identified population-specific susceptibility factors of which the best example is the Ashkenazi Jewish specific haplogroup N1b1, having an apparent protective effect against T2DM complications in Ash (p = 0.006), being absent in the NAF population and under-represented in the Seph population. We have generated and analyzed whole mtDNA sequences from the disease associated haplogroups revealing mutations in highly conserved positions that are good candidates to explain the phenotypic effect of these genetic backgrounds.


Our findings support the possibility that recent bottleneck events leading to over-representation of minor mtDNA alleles in specific genetic isolates, could result in population-specific susceptibility loci to complex disorders.