Biology subjects

Aulchenko, Y.

Publications and source records attributed to Aulchenko, Y..

3 recordsLinked to original sources

bioRxiv2018

Defining the genetic control of human blood plasma N-glycome using genome-wide association study

Glycosylation is a common post-translational modification of proteins. It is known, that glycans are directly involved in the pathophysiology of every major disease. Defining genetic factors altering glycosylation may provide a basis for novel approaches to diagnostic and pharmaceutical applications. Here, we report a genome-wide association study of the human blood plasma N-glycome composition in up to 3811 people. We discovered and replicated twelve loci. This allowed us to demonstrate a clear overlap in genetic control between total plasma and IgG glycosylation. Majority of loci contained genes that encode enzymes directly involved in glycosylation (FUT3/FUT6, FUT8, B3GAT1, ST6GAL1, B4GALT1, ST3GAL4, MGAT3, and MGAT5). We, however, also found loci that are likely to reflect other, more complex, aspects of plasma glycosylation process. Functional genomic annotation suggested the role of DERL3, which potentially highlights the role of glycoprotein degradation pathway, and such transcription factor as IKZF1.

genetics↗

bioRxiv2018

Identification of 12 genetic loci associated with human healthspan

The mounting challenge of preserving the quality of life in an aging population directs the focus of longevity science to the regulatory pathways controlling healthspan. To understand the nature of the relationship between the healthspan and lifespan and uncover the genetic architecture of the two phenotypes, we studied the incidence of major age-related diseases in the UK Biobank (UKB) cohort. We observed that the incidence rates of major chronic diseases increase exponentially. The risk of disease acquisition doubled approximately every eight years, i.e., at a rate compatible with the doubling time of the Gompertz mortality law. Assuming that aging is the single underlying factor behind the morbidity rates dynamics, we built a proportional hazards model to predict the risks of the diseases and therefore the age corresponding to the end of healthspan of an individual depending on their age, gender, and the genetic background. We suggested a computationally efficient procedure for the determination of the effect size and statistical significance of individual gene variants associations with healthspan in a form suitable for a Genome-Wide Association Studies (GWAS). Using the UKB sub-population of 300,447 genetically Caucasian, British individuals as a discovery cohort, we identified 12 loci associated with healthspan and reaching the whole-genome level of significance. We observed strong (|{rho}g| > 0.3) genetic correlations between healthspan and the incidence of specific age-related disease present in our healthspan definition (with the notable exception of dementia). Other examples included all-cause mortality (as derived from parental survival, with{rho} g = -0.76), life-history traits (metrics of obesity, age at first birth), levels of different metabolites (lipids, amino acids, glycemic traits), and psychological traits (smoking behaviour, cognitive performance, depressive symptoms, insomnia). We conclude by noting that the healthspan phenotype, suggested and characterized here, offers a promising new way to investigate human longevity by exploiting the data from genetic and clinical data on living individuals.

epidemiology↗

bioRxiv2017

Coat color allele and mtDNA haplotype distributions in Russian cat populations: a citizen-science research

This work has started as a project for the summer school in molecular and theoretical biology. Efficient teaching and learning modern methods of molecular biology and population genetics in a two-week study course for high school students needs an attractive subject. We chose phylogeography of the domestic cat as the subject of our project because 1) everybody likes cats; 2) cats are polymorphic for several coat color mutations, which can be easily detected by street survey or in the photographs; 3) samples for DNA extraction are easy to collect without posing ethical and biosafety problems; 4) rich background information of geographical distribution of coat color alleles and variation in mtDNA is available; 5) phylogeography of cat population in Russia is poorly studied and therefore new data collected in this large territory may shed a light on the global cat distribution and on the origin of the fancy breeds.\n\nDuring the project students studied coat color and mitotype distribution across Russian random bred cats. The basics of field (observations of natural cat populations, hair collection), formal (inheritance of coat colors), mathematical population (allele frequency distributions and their comparisons, building phylogenetic trees, multidimensional scaling), and molecular (DNA extraction and amplification, quality control of DNA sequencing data) genetics were covered.\n\nWe scored coat color phenotypes in 1182 cats and sequenced mtDNA control region from hair samples of 38 cats from 18 geographical sites. Analysis of coat color alleles frequencies and mitotype distribution confirmed relative homogeneity of gene pools of Russian cat populations, indicating their recent origin. We found several unique mitotypes and demonstrated that OL1 mitotype, previously found only in Siberian fancy breed, was present in random bred cats from several Russian cities. This contributes to the discussion on the origin of the Siberian breed of cats, and supports the view that Siberians is a recent breed created in the 1980s by breeding of selected representatives of the random bred population.

genetics↗