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

Normal variation, population genetics, genetic epidemiology
ability and mortality. The global distribution of the genetic polymorphisms
associated with cardiovascular diseases has been widely investigated
and regional variations have been observed. The Azorean
population is known to be of heterogeneous origin and represents the
Portuguese region with the highest mortality rate caused by CVD.
Based on this fact we have analysed allelic and genotypic frequencies
in 10 candidate genes.
Material and Methods: A representative sample of the population was
obtained by randomly recruiting 155 unrelated subjects from Terceira
Island. Genomic DNA was extracted from whole peripheral blood by
salting-out. Identification of genetic polymorphisms was performed by
polymerase chain reaction (PCR) followed by reverse hybridization
(CVD StripAssay, ViennaLab Diagnostics GmbH). Genotype distributions
were tested for Hardy-Weinberg equilibrium. Chi-square tests
were used to evaluate statistical significant differences between our
population and other Caucasian populations.
Results: Allelic and genotypic frequencies are presented in table 1.
Genetic polymorphism Alleles % Genotypes %
FV G1691A (leiden) A 0.97
GA
AA
1.94
0.0
FV H1299R (R2) R 9.68
HR
RR
18.06
0.65
PTH G20210A A 1.94
GA
AA
3.87
0.0
FactorXIII V34L V 75.48
VL
VV
41.29
54.84
FGB-455G-A A 18.06
GA
AA
30.97
2.58
PAI-1 4G/5G 4G 45.48
4/5
4/4
43.23
23.87
HPA-1a/b b 18.71
ab
bb
28.39
4.52
MTHFR C677T T 30.97
CT
TT
46.45
7.74
MTHFR A1298C C 32.58
AC
CC
47.10
9.03
ACE I/D D 61.61
ID
DD
53.55
34.84
ApoB R3500Q Q 0
RQ
QQ
0
0
2/2 1.29
Apo E
E2
E3
E4
6.13
81.29
12.58
2/3
2/4
3/3
3/4
9.03
0.65
65.81
21.94
4/4 1.29
Conclusion: We report the prevalence of various genetic CVD risk factors for the first
time in the Azorean population. The frequencies obtained in our population are within
the range of frequencies reported on other European populations. The high frequency
of cardiovascular disease may be possibly related with other genetic or environmental
factors not evaluated in this report.
P1144. Carrier frequency of cystic fibrosis transmembrane
conductance regulator gene mutations in the general Moroccan
population
I. Rratbi1,2 , M. Legendre3 , A. Le Floch3 , S. Deqaqi Cherkaoui1 , C. Costa3 , M.
Goossens3 , A. Sefiani1 , E. Girodon3 ;
1 2 department of medical genetic, rabat, Morocco, Service de Biochimie et
Génétique, AP-HP et INSERM U654, Hôpital Henri-Mondor, Creteil, France,
3Service de Biochimie et Génétique, AP-HP et INSERM U654, Hôpital Henri-
Mondor, creteil, France.
OBJECTIVE: Epidemiology of cystic fibrosis (CF), the most common
lethal genetic disease in the Caucasian population, is poorly known in
North African populations. No data is available on the native Moroccan
population. We aimed to identify possible CF carriers in a sample
of the general Moroccan population. METHODS: Blood samples from
150 unrelated healthy Moroccans with no symptoms of CF were tested
for 33 frequent CF mutations and the intron 8 polyT variant using a
commercial assay. RESULTS: Two subjects were found to be carriers
for the F508del mutation and eight others were heterozygous for the
(T)5 variant of intron 8. CONCLUSION: These findings indicate that
the Moroccan population is at risk for CF and related diseases. The
CF incidence could be in the range of that found in European populations.
Larger studies are necessary to identify the clinical pattern and
accurately determine the incidence and the molecular basis of CF in
Morocco.
P1145. The frequency of CFTR mutations at patients from
Romania - a collaborative study
L. Pop 1 , L. Tamas 2 , I. Popa 1 , Z. Popa 3 , C. Samoila 2 , M. Motoc 2 , E. Seclaman 2 , I.
M. Popa 1 , G. Benga 4 , L. Dracea 5 , S. Mosescu 6 , E. Tomescu 7 ;
1 Clinic II of Pediatrics, University of Medicine and Pharmacy, Timisoara, Romania,
2 Biochemistry Department - University of Medicine and Pharmacy, Timisoara,
Romania, 3 National Center of Cystic Fibrosis from Timisoara, Timisoara,
Romania, 4 Departament of Genetics and Molecular Biology – University of Medicine
and Pharmacy, Cluj Napoca, Romania, 5 Pediatric Clinic – Faculty of Medicine,
Brasov, Romania, 6 Children Emergency Hospital “Grigore Alexandrescu”,
Bucharest, Romania, 7 Hospital Children “Alfred Rusescu”, Bucharest, Romania.
Objectives: The aim of this study was to estimate the frequency of
cystic fibrosis mutations detected in patients from the National Center
of Cystic Fibrosis from Timisoara (NCCFT).
Method
Based on clinical findings and pathological sweat test values, 120
patients (240 alleles) were selected. DNA was isolated from biological
samples (blood, amniotic fluid) and the genetic analysis was performed
using the Elucigene CF29 kit, direct PCR products sequencing
and RFLP. 74 patients were investigated in collaboration with Royal
Manchester Children’s Hospital - Genetic Unit (UK) and 46 patients by
our own laboratory (Biochemistry Department - UMF Timisoara)
Results
21 CFTR mutations (ΔF508, 2183 AA>G, W1282X, 1898+1G>A, I148T,
621+1G>T, G576X, 1717-2A>G, R553X, R735K, CFTRdel2,3(21kb),
G542X, G817V, 3272-26A>G, 457TAT>G, 3849+10kbC>T, R1162X,
N1303K, 3849G>A, S1235R, R117H) and four polymorphic variants -
2694T/G, 2694T/C, IVS8-5T, IVS8-7T were identified (2 new mutations
- R735K and 1717-2A>G).
Conclusions
The most frequent mutations in Romania are ΔF508 (51,66%), G542X
(2,91%), 621+1G>T (1,65%) and N1303K (1,25%). The rest of non-
ΔF508 mutations had a frequency lower than 1%. The results show
a similarity with the situation from Western Europe and the rest of the
world where the most frequent mutations are also ΔF508 and G542X.
However, the lower frequency for ΔF508 mutation and the great number
(30%) of the alleles who could not be identified (from heterozygous
patients with one identified mutation) are probably due to the genetic
heterogeneity of Romanian population and to incomplete genetic analysis
for rare mutations.
(Study performed through Research Grants - CEEX 5855 and CNC-
SISA/1188/2004-2006)
P1146. Genetic variation at D3S1358, D5S818 and D13S317 loci
in Russian Siberian population
O. Odinokova;
Institute of Medical Genetics, Tomsk, Russian Federation, Tomsk, Russian
Federation.
STR loci represent a rich source of highly polymorphic markers for
medical, forensic and population studies. There are notable differences
in allele frequencies and heterozygosities between population
groups. We present here characteristics of the allelic polymorphism for
three STRs loci: D3S1358, D5S818 and D13S317 in Russians (Caucasians)
living in South-West Siberia.
Allele typing was performed using PCR and subsequent high-resolution
PAAG electrophoresis. We have analysed DNA samples from unrelated
subjects: 262 individuals were tested for D3S1358, D13S317
STR-systems and 360 individuals were tested for D5S818. Eight alleles
were identified in D3S1358 (13-20 repeats, 118-146 bp) and
D13S317 loci (8-15 repeats, 169-197 bp); and nine alleles were note
in D5S818 (7-15 repeats, 134-166 bp) locus. Genotype frequency
distributions were consistent with Hardy-Weinberg equilibrium for
every STR-systems. The level of observed heterozygosity was high:
0,821 (D13S317), 0,782 (D3S1358), and 0,769 (D5S818). Polymorphism
information content (PIC) and discrimination power (pD) were:
PIC=0,76, pD=0,923 for D13S317; PIC=0,74, pD=0,913 for D3S1358;
and PIC=0,70, pD=0,891 for D5S818; power of exclusion (W) and
marching probability (pM) - 0,638 and 0,077 in D13S317; 0,567 and
0,087 in D3S1358; 0,544 and 0,109 in D5S818, consequently.
The frequency data obtained can be used for comparison to other populations.
Forensic efficiency data suggest that investigated markers
D3S1358, D5S818 and D13S317 are very discriminating in Russian
Siberian population.
2