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

Normal variation, population genetics, genetic epidemiology
mictic population of Bucharest and the partial isolated population from
Prahova Valley.
Genetic distance analysis showed a close genetic relationship with
Italian population as well as with Greek population groups.
Historically this could be the result of intense trading activities of Thracian
tribal groups and Greek population groups who established trading
colonies at the west coast of the Black Sea (actually East-Romania)
during the 7 th - 8 th century. The most of the Italian influence is thought
to be the result of the occupation of the Danube region during the time
of the Romanian Empire. A small Slavic influence was also found. The
genetic distance between Romanian and German, Croatian, as well as
Hungarian populations were more significant.
The results can also be used for paternity and forensic analyses in the
Romanian population.
P1222. Beta Thalassemia in Iran: Genetic admixture, new
theories for origin and migration of some mutations
M. M. Banoei, M. Houshmand, M. Shafa Sharait Panahi;
National Institute for Genetic Engineering and Biotechnology, Tehran, Islamic
Republic of Iran.
Background: Iran as one of the Middle East country consists of multiethnic
groups that have been influenced by various invasions and
migration throughout history. In the eastern Mediterranean region, Iran
is one of the major centers for the prevalence of β- Thalassemia. This
review is an attempt to study the origin of β- Thalassemia mutations in
different parts of Iran.
Methods: Through review and discussion of research literature and
referred patients to our center, we compared the frequencies of β -
globin mutations in different regions of Iran with those derived from
neighboring countries.
Results: The analysis provided evidence of new theories about the
origin and migration of some mutations like -25bp del, CD36/37, CD30
and introduction of IVSI-5 to outside, as well as, the remarkable genetic
classification of the Iranian people and ethnic groups.
Conclusions: This review represents reflection of historic events due
to genetic admixture and roles of invasions and migrations in this phenomenon.
Also distribution of β- globin gene mutations in Iran showed
high heterogeneity among the population in comparison with other
population that this heterogeneity has been derived originally from a
population with an ethnic Aryan background.
P1223. A Novel β-thalassemia mutation in the distal promoter of
the β-globin gene
I. Agouti 1 , C. Badens 2 , F. Sayah 1 , A. Barrakat 1 , M. Bennani 1 ;
1 laboratoire de Biologie Appliquée, Faculté des Sciences et Techniques, Tanger,
Morocco, 2 Laboratoire de Génétique Moléculaire, Hôpital de d’Enfant de la
Timone, Marseille, France.
A patient with β-thalassemia intermedia of Moroccan descent was
found to be compound heterozygous for a novel β-thalassemia muta-
tion G→A at position -190 5’ to the β-globin gene and a previously
described β 0 -thalassemia allele frame shift codon 6 (-A). The novel
mutation was found to be associated with the Mediterranean β haplotype
IX [- + - + + + +].
The mother, who has the -190 G→A mutation as the sole abnormality
of the β-globin gene, had normal hemoglobin, red blood cell indices
and HbA 2 levels. Thus the -190 G→A mutation is silent.
The possibility that the novel -190 G→A substitution is a simple polymorphism
in the β-globin gene was considered, but is unlikely given its
presence in a region (-50 to -300) where other promoter elements important
for differential control of gene expression have been described
and the absence of this substitution in 80 other normal chromosomes.
Although functional tests of the cloned gene in suitable expression assays
will be needed to prove that the change at position -190 is a mutation
rather than a simple polymorphism.
P1224. Allele frequencies of two novel tandem repeat
polymorphism of the 5’-untranslate region of the human CYP2E1
gene
C. Gräbsch, O. Herbarth, H. E. Wichmann, U. Krämer, M. Bauer, the LISA
study group;
Helmoltz Centre for Environmental Research - UFZ, Department for Human
Exposure Research and Epidemiology, Leipzig, Germany.
The ethanol inducible human cytochrome P4502E1 (CYP2E1) plays
a key role in the metabolic activation of procarcinogens like aniline,
vinyl chloride as well as acryl amide. CYP2E1 activity depends on
inter-individual genetic polymorphisms as well as on interactions at
translational level. Homozygotes for CYP2E1*1D allele have got an
increased enzyme activity compared to the CYP2E1*1C allele.
In order to examine the relationship between pollutant -induced clinical
outcomes and genetic polymorphisms 1003 Caucasians of the LISA
epidemiological study were genotyped for enzymes of biotransformation.
Regarding CYP2E1, a repeat in the 5’-untranslated region at -2178
to -1945 bp has been analyzed in more detail by allele specific PCR.
Besides the expected alleles CYP2E1*1A (5 repeats), CYP2E1*1C (6
repeats, wt) and CYP2E1*1D (8 repeats) with a frequency of 0.4%,
97.4% and 2.1%, two novel alleles could be described by the present
work.
The first novel allele (Acc-No. AM503355) contains 7 repeats and appears
with a frequency of 0.05%. This allele is heterozygous expressed
with the CYP2E1*1C.
The second novel allele contains 8 repeats and exclusively appears
concomitantly with the CYP2E1*1D allele (frequency 2.1%), which is
heterozygous expressed mainly with the CYP2E1*1C or rarely with
the CYP2E1*1A allele. At the moment it is not clear whether the novel
polymorphisms of the 5’-flanking region alter the CYP2E1 expression.
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