Institute Cytology and Genetics

Laboratory of Molecular Human Genetics

Head R.I.Sukernik, Dr.Biol.Sci.

Main research directions of the Laboratory are:

1. Analysis of variability in mitochondrial and nuclear DNAs in aborigenes of Siberia with reference to the evolutionary history of North Eurasia and North America.

2. Epidemiology of mitochondrial mutations with pathological effects in human populations in Siberia and their significance to selection.

The research goal of the main project is the obtaining of fundamental data on mtDNA variability and evolution, the HLA-genes, and on the hypervariable region of the Y chromosome in territories of Siberia, from the Priuralie (the areas adjacent to the Urals) the coast of the Bering and Okhotsk seas and to the lower Amur river.

The accompanying scientific research project is aimed at the detection of mtDNA mutations with pathological effects, the determination of their expression features and of their role in microevolution in populations of West Siberia. This topic is being developed in collaboration with the Center of Molecular Medicine, the Amori University, Atlanta, USA (Director D.K.Wallace) and the Division of Immunogenetics of the Max Plank Institute, Tubingen, Germany (Director I.Klein). The data provided the broadening and improvement of the existing notions of the genetic history of Siberian ethnic groups, Kets, Evenks, Yukaghirs, Chukchees, Asian Eskimos, Koriaks, Itelmens, Nivkhs, Udegeis, Negildalts to elucidate problems related to the earliest settlement of the New World and to its colonization by man. Search for mitochondrial mutations with pathological effects revealed 6 families in which atrophy of the optic nerve is maternally inherited. In 3 of the families, mutations known in the literature in association with Leber's disease were identified: primary mutations 3460 and 11778 (heteroplasmy), mutation of intermediate risk 15257 and secondary mutations 4216, 13708, 15812. It is noteworthy that a substitution at position 11778 was found in the pedigrees of two families, in one of which the substitution was in the state of heteroplasmy. In the affected and healthy members of the other three families, without the above mutations, the following candidate mutations were investigated: MTND1*LHOH3635, MTND2*LHOH4640, MTCOI*LHOH6445.

The criterion for the cause-effect relation was the ability of these mutations to cause substitutions in the conserved amino acids in the subunits of complexes I and IV, as well as a decrease in the respiratory function and in the activities of oxidative phosphorylation enzymes of these complexes.