2009 Vienna - European Society of Human Genetics

Evolutionary and population genetics, and Genetic epidemiology
GSTM1 could be protective concerning alcoholic cirrhosis and cirrhosis
of mixed etiology.
P10.28
Distribution of polymorphisms in genes for interleukins and
their receptors in different ethnic groups of siberia
N. P. Babushkina, E. Y. Bragina, A. A. Rudko, A. N. Kucher;
Institute of Medical Genetics, Tomsk, Russian Federation.
Distribution of polymorphisms in genes IL4 (rs2243291), IL4RA
(rs1801275 and rs2074570), IL12A (rs568408), IL12B (rs3212227 and
rs3212220) and IL12RB1 (rs3746190 and rs11575926) in four ethnic
groups of Siberian region (the immigrant Caucasian population - Russians,
and indigenous Mongoloid populations - Yakuts, Tuvinians,
Buryats; 96 individuals in each group) was studied.
Comparison of allelic frequencies with the data on other populations
worldwide [http://www.ncbi.nlm.nih.gov] has shown that for six out of
eight investigated SNPs the frequencies were beyond the values known
for Caucasians and Mongoloids (except for IL4RA (rs1801275) and
IL12B (rs3212220)). Allelic frequencies for SNPs in IL4 (rs2243291),
IL4RA (rs2074570), IL12RB1 (rs11575926), IL12B (rs3212220) are
significantly different between Russian and indigenous populations of
Siberia. For two SNPs (rs3746190 in gene IL12RB1 and rs3212227
in gene IL12B) ethnic differences in distribution of allelic frequencies
were shown. No ethnic specificity was shown for distribution of allelic
frequencies for rs568408 in IL12A and rs1801275 in IL4RA. According
to pairwise F ST values calculated for studied SNPs in four ethnic
groups, the extent of genetic differentiation in Siberia makes up 3.71
%. We observed that only Buryats and Yakuts do not show statistically
significant distinctions in their genetic structure.
The results once again testify high genetic heterogeneity of ethnic
groups in Siberian region which has to be considered while planning
genetic-epidemiological studies of common diseases.
P10.29
X-chromosomal haplotypes in global human populations
V. A. Stepanov, I. Y. Khitrinskaya;
Institute for Medical Genetics, Tomsk, Russian Federation.
To reconstruct the origin and evolution of X-chromosomal lineages
in global human populations we investigated the genetic diversity in
23 population samples (about 1500 individuals totally) using SNP
markers in a single linkage disequilibrium region of ZFX gene. About
sixty haplotypes belonging to 3 phylogenetic branches (A, B, and F)
originated from the single African root were found in the total sample.
Branch A includes mostly African haplotypes, whereas four major haplotypes
belonging to different sub-branches of B (haplotype E8) and F
(haplotypes H4, I3 and I11) were present in Eurasia. Major haplotype
of the older branch B (E8) is almost evenly distributed among Eurasian
populations. Haplotypes of the younger phylogenetic branches
demonstrates clinal distribution with the sharp frequency changes
from East to West. Haplotype H4 is presumably “Eastern-Eurasian”. It
reaches the highest frequency in Eastern and South-Eastern Asians.
Haplotypes I3 and I11 in the contrary show the clear frequency gradient
from West to East with the highest frequency in Europeans, moderate
frequency in Central Asia, and the minimal frequency in North-East
and South-East Asia. The total level of genetic differentiation of global
human populations estimated by the analysis of molecular variance of
X-chromosomal haplotypes (Fst = 9.1%) is quite high and roughly corresponds
to those measured for most other types of genetic markers
except Y-chromosomal haplogroups which are characterized by the
much higher level of between-population differences.
P10.30
Genetic Position of Bucharest region (Romania) in the
According to Eight DNA markers
M. L. Toma1 , M. Stavarachi1 , D. Cimponeriu1 , P. Apostol1 , M. Cojocaru1 , N.
Panduru2 , I. Radu1 , L. Gavrila1 ;
1 2 Institute of genetics, Bucharest, Romania, “Prof. N. C. Paulescu” Institute of
Diabetes, Nutrition and Metabolic Diseases, Bucharest, Romania.
Historically, the Bucharest city that was founded at the end of XIV century
played a key role as a trade route for south-eastern civilization,
and it has been the setting for numerous conquests and demographic
expansions.
In this work, eight DNA markers (rs4646994, rs61722009, rs7975232,
rs731236, rs2228570, rs1544410, rs1801133, rs1805087) were typed
in 100 unrelated individuals (sex ratio 60:40) from Bucharest region
(Romania). Aim was to analyze the genetic variability and to establish
the relation between this region and other European populations.
Allele frequencies were calculated by direct counting; Hardy-Weinberg
equilibrium was assessed by an exact test. Gene diversity for
each population was calculated. Genetic distances matrices were represented
using Nei’s method by PHYLIP 3.68 package. Tree topology
was inferred using the Neighbor-Joining method and assessed
through 1,000 bootstrap iterations.
In our lot, the most common polymorphism was MTR-rs1805087
(82.5%) and the least frequent was VDR- rs731236 (50%). The gene
diversity compute was 0.545. Polymorphism’s frequencies were similar
to the mean frequencies calculated for the whole set of populations
included in the study. The most affiliated population with our lot are
Italy, Spain, Poland, Germany, Greece and Turkey the most distant
population are United Kingdom, Sweden, Croatia and Slovacia.
This study indicates that data on SNPs provide information about the
evolutionary history of human populations. In the future other genetic
markers will be studied to be compared with the results obtained in
neighboring populations to elucidate more precisely the genetic structure
of this region of the Balcanic Peninsula.
P10.31
Genetic differences between four European populations
V. Moskvina 1 , M. Smith 1 , D. Ivanov 1 , International Schizophrenia Consortium,
D. Blackwood 2 , C. Hultman 3 , M. Gill 4 , A. Corvin 4 , C. O’Dushlaine 4 , M.
O’Donovan 1 , M. Owen 1 , G. Kirov 1 ;
1 Cardiff University, Cardiff, United Kingdom, 2 University of Edinburgh, Edinburgh,
United Kingdom, 3 Karolinska Institute, Stockholm, Sweden, 4 Trinity College
Dublin, Dublin, Ireland.
Population stratification can distort the results of genome-wide association
studies (GWAS). One approach to deal with this inflation of
the statistic is to estimate the inflation factor and adjust the detection
statistic accordingly. However, the evolutionally forces work with different
strength in some regions of the human genome, e.g. around the
lactase gene (LCT) and the HLA region, making such an adjustment
inappropriate.
We examined the population differences in four European populations
(Scotland, Ireland, Sweden and Bulgaria) using data from GWAS performed
with the Affymetrix 6.0 array at the Broad Institute. We show
that there are >20,000 SNPs which are highly (p