Human Genetics Section
David Schlessinger, PhD, Chief
The Human Genetics Section (HGS), led by David Schlessinger, studies genetic and epidemiological factors in aging-related traits with two approaches: 1) defining the relation of early development to aging in model organ systems; and 2) longitudinal study in the favorable population of the island of Sardinia. Early development sets up for each organ the critical reserve of terminally differentiated cells whose maintenance and loss determine the course of aging. Thus, knowledge of fetal development of ovarian follicles, for example, has led to approaches to delay menopause in mouse models by increasing the size of the initial reserve or slowing the rate of its utilization. In addition, in a step toward the goal of regenerative medicine, HGS has shown that particular transcription factors can direct the differentiation of embryonic stem cells to several neural cell types. The SardiNIA study analyzes the course of aging at the individual and population levels since 2001, focusing on (1) menopause, (2) kidney, heart, and personality traits, and (3) detailed analyses of age-related autoimmunity and immunosenescence of subtypes of immune cells.
The Section provides Core analyses of statistical analyses, both with standard methods and with new algorithms. New programs are designed to analyze rates of aging, pleiotropic effects of DNA variants, and consequences of variation in two multi-copy components of human genetic endowment – mitochondrial DNA and ribosomal DNA sequences.
- Development and aging of skin exocrine glands.
- Development of ovarian follicles in relation to menopause.
- Role of PLAC1 in fetal well-being and development.
- Imaging-based analysis of eye microvasculature in relation to aging and macular degeneration.
- Mitochondrial copy number and variants in aging and aging-related diseases.
- Ribosomal DNA copy number and variation in aging.
- Immunosenescence of subtypes of immune system cells.
- Genetic variants in Multiple Sclerosis and Type 1 diabetes.
- Senescence of cardiovascular and renal systems.
Recent Publications at PubMed
Findings and Publications
Pelosi, E., Omari, S., Michel, M., Ding, J., Amano T, Forabosco A, Schlessinger D, and Ottolenghi C. Constitutively active Foxo3 in oocytes preserves ovarian reserve in mice. Nature Communications 4: 1843, 2013.
Pelosi E, Forabosco A, and Schlessinger D. Genetics of the ovarian reserve. Frontiers in Genetics 6:308. Review, 2015.
Cui, C.Y., Ishii, R., Campbell, D.P., Michel, M., Pial, Y., Kume, T., and Schlessinger, D. Foxc1 ablated mice are anhidrotic and recapitulate features of human miliaria sweat retention disorder. J Invest Dermatology 137:38-45, 2017.
Steri, M., Orrù, V., Idda, M.L., Pitzalis, M., et al. Overexpression of the cytokine BAFF and autoimmunity risk. New England Journal of Medicine 2017.
Qian, Y., Butler, T.J., Opsahl-Ong, K., Giroux, N.S., Sidore, C., Nagaraja, R., Cucca, F., Ferrucci, L., Abecasis, G.R., Schlessinger, D., and Ding, J. fastMitoCalc: an ultra-fast program to estimate mitochondrial DNA copy number from whole genome sequences. Bioinformatics (in press) Jan 29. 10.1093/bioinformatics/btw835, 2017.