European Human Genetics Conference 2007 June 16 – 19, 2007 ...

Normal variation, population genetics, genetic epidemiology
P1147. Social aspects of deafness in the Republic Altai (south
Siberia, Russia)
O. L. Posukh;
Institute of Cytology and Genetics, Novosibirsk, Russian Federation.
Hereditary hearing impairment is a heterogeneous disability with different
pattern of inheritance. The GJB2 (Cx26) mutations account for
more than a half of recessive deafness in many populations. Prevalence
of particular GJB2 mutations depends on ethnic origin, specific
structure and history of population. Specific social traditions, e.g. the
assortative marriage rates among deaf people, have been suggested
to influence frequency of Cx26 deafness. Previously, we revealed the
GJB2 mutational diversity in Altai Republic which population (~200,000)
includes three major ethnicities: indigenous Altaians (~60,000), Russians
(~120,000), and Kazakhs (~12,000). Mutations c.35delG and
c.235delC were found to be causative factors among Russian and
Altaian patients, respectively. Cx26 deafness was detected in considerable
proportion of affected Russian families whereas many Altaian
multiplex families were found to be Cx26-negative. High carrier rate of
c.235delC was detected in Altaian hearing controls. This study firstly
evaluates the marriage patterns in deaf and hard hearing population
in Altai Republic. Informative data was obtained on 112 adults with
early onset of hearing impairment equally represented citizens (57)
and villagers (55). Rural people constitute 3/4 of total Republic Altai
population whereas the others live in the capital Gorno-Altaisk, the
only city in the Republic. We revealed assortative mating rate of 0.45 in
rural sample, much lower as compared to 0.84 in urban sample. Ethnic
diversity, traditional Altaian marriage pattern reducing consanguinity
rate, and social differences between urban and rural population could
influence the prevalence of deafness in Republic Altai.
This work is supported by the Russian Foundation for Humanitarian
Research (07- 06-00765a).
P1148. Case-Control Study of Libyan and Maltese Patients with
Type II Diabetes Mellitus
A. A. Al Ashtar 1 , J. Azzopardi 2 , S. Bezzina Wettinger 1 , J. Borg 1 , W. Cassar 1 , R.
Galdies 1 , C. A. Scerri 1,3 , J. Vassallo 2 , A. E. Felice 1,3 ;
1 Laboratory of Molecular Genetics, Msida, Malta, 2 Diabetes Clinic, St Luke’s
Hospital, G’Mangia, Malta, 3 Thalassaemia Clinic, Div. of Pathology, St Luke’s
Hospital, G’Mangia, Malta.
Type II Diabetes Mellitus (DMTypeII) is a common disease with onset
in middle-aged individuals, caused by an imbalance between insulin
production and action. Single nucleotide polymorphisms (SNPs) and
mutations in different genes may be implicated in developing DMTypeII.
In this study we analyzed 9 such genes that include IPF, MTHFR,
mitochondrial tRNA, Resistin, PPP1R3, ADRABbeta2, MIF, PTPN1
and TLR4. SNPs were chosen from each gene according to stringent
criteria based on developing DMTypeII in other populations. SNPs
were genotyped in the Libyan and Maltese patients and compared
with healthy Maltese citizens. DNA was extracted from whole blood,
and genotyping of each gene determined by PCR-RFLP. Concurrently,
pools of DNA from random Maltese newborn were carried out using
fluorometry for accurate quantification. All genes were in Hardy-Weinberg
Equilibrium and statistical analysis was carried out by SPSS (student
package 12). Chi square analysis of all data in between populations
and across populations revealed a significant association of the
ADRABbeta2 gene of both Libyan and Maltese DMTypeII patients with
healthy Maltese controls (p < 0.05 for both). There is no difference between
Libyan and Maltese Diabetics (p=0.07) indicating that this gene
has a common predisposition to both populations. On the other hand,
IPF gene was only associated with the Libyan DMTypeII and not with
the Maltese population (p < 0.05). All other genes were not statistically
significant associated with DMTypeII. The results show a strong association
of the ADRABbeta2 (Arg16Gly) and IPF (missense mutation
Cys18Arg) genes with DMTypeII.
P1149. Cytogenetic and cancerogenic effects of low dose
radiation among liquidators in the Chernobyl accident area
E. Dyomina;
R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology
, Kyiv, Ukraine.
The purpose of the presented study was to estimate influence of the
absorbed dose values on the cytogenetic effects and risk of malignant
formation (MF) in group of liquidators.
The method of “internal comparison” made it possible to study epidemiological
parameters in dependence with the documented exposure
doses for 17 thousand liquidators. The cytogenetic examinations of
500 liquidators were carried out. The dose dependence of MF frequency
was studied with the application of piecewise-linear splines
and hypothesis about the equality of two probabilities on the basis of
the statistical criterion 2S.
Tendency toward reduction in the frequency of MF with increase of
the dose in the interval of 1-85 cGy for both the age groups (younger
and older than 40 years) was observed. Probability of random event
when the liquidators with MF were exposed to dose in the ranges from
1 to 3 cGy or from 3 to 5 cGy statistically significantly exceeds the
appropriate probability for the whole cohort . Statistically significant differences
in the probabilities for other classes of diseases within dose
ranges were not observed. In spite of the promote terms of cytogenetic
analysis and partial elimination of dicentric chromosomes from blood
„dose- effect“ dependence for aberrations remains in the group of liquidators
with MF.
Our cytogenetic investigations revealed the tendency to increasing of
MF frequency in group of liquidators exposed to low doses. The retention
of „dose- effect“ dependence for the dicentrics in lymphocytes of
liquidators with MF within promote postradiation periods was established.
P1150. Allele frequencies for the fifteen short tandem repeat loci
in Croatian population
V. Skaro 1 , P. Projic 1 , N. Pojskic 2 , A. Durmic 2 , L. Kovacevic 2 , S. Haveric 2 , D.
Primorac 3 , D. Marjanovic 1,2 ;
1 Center for Integrative Genomics, Molecular Diagnostics, Cell and Gene Therapy,
“Rudjer Boskovic” Institute, Zagreb, Croatia, 2 Institute for Genetic Engineering
and Biotechnology, Sarajevo, Bosnia and Herzegovina, 3 Medical School at
Osijek University, Osijek, Croatia.
We have analyzed the distribution of allele frequencies at fifteen autosomal
short tandem repeats loci in the representative sample of Croatians.
A total of 110 unrelated individuals (Caucasians) born in Croatia
have been sampled for the analysis. All of them have been voluntary
donors. Buccal swab have been used as the DNA source. Specimens
were air-dried, placed in 1,5 ml tubes, and immediately transported to
the laboratory. The samples have been stored at -20 o C until beginning
of DNA analysis. The Qiagen Dnaeasy TM Tissue Kit was used for DNA
extraction. The AmpFlSTR ® Identifiler ® (ABI, Foster City, CA) has been
used to simultaneously amplify by PCR 15 STR loci. The STR loci are:
D3S1358, TH01, D21S11, D18S51, D2S1338, D5S818, D13S317,
D7S820, D16S539, CSF1PO, D19S433, vWA, D8S1179, TPOX, and
FGA. Similar amount of DNA (approx. 1 ng) was used in all PCR reactions.
Total reaction volume was 12,5 μl. The PCR amplification
has been carried out in PE Gene Amp PCR System Thermal Cycler
(ABI, Foster City, CA) according to the manufacturer’s recommendations.
Electrophoresis of the amplification products was preformed on
an ABI PRISM 3130 genetic analyzer Raw data have been compiled,
analyzed and numerical allele designations of the profiles were obtained
by using the accessory software: ABI PRISM ® Data Collection
Software v3.0 and GeneMapper ΤΜ ID Software v3.1. Deviation from
Hardy-Weinberg equilibrium, observed and expected heterozygosity,
power of discrimination and power of exclusion were calculated. Also,
we have compared our data with data obtained from geographically
neighboring European populations.
P1151. Gene expression variation of HSA21 genes in normal and
Down syndrome (DS) individuals: understanding phenotypic
variability in DS patients.
P. Prandini 1 , S. Deutsch 1 , R. Lyle 2 , M. Gagnebin 1 , C. Delucinge Vivier 3 , M.
Delorenzi 4,5 , C. Gehrig 1 , P. Descombes 3 , S. Sherman 6 , F. Bricarelli 7 , C. Baldo 7 ,
A. Novelli 8 , B. Dallapiccola 8 , S. E. Antonarakis 1 ;
1 University of Geneva, Geneva 4, Switzerland, 2 Department of Medical Genetics,
Ullevål University Hospital, Oslo, Norway, 3 NCCR Frontiers in Genetics,
Genomic Platform, Geneva 4, Switzerland, 4 Swiss Institute of Bioinformatics
(SIB), Lausanne, Switzerland, 5 Swiss Institute of Experimental Cancer Research
(ISREC), Epalinges, Switzerland, 6 Emory University School of Medicine,
Atlanta, GA, United States, 7 E.O. Ospedali Galliera di Genova, Genova, Italy,
8 University La Sapienza, Rome, Italy.
Down Syndrome (DS) individuals display considerable phenotypic
variability. Since DS is a disease caused by alterations of gene dos-
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