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

Genetic analysis, linkage, and association
tory ERPs. ERP recordings of each polymorphic group were analyzed
in the time domain by measuring P300 amplitude and latency, and
furthermore, in the time-frequency domain by decomposition of ERP
signals by using wavelet transform with analysis of variance (ANOVA).
Results provide evidence of strong effect of GABRG2 polymorphism
with ERP characteristics both in time domain and in time-frequency
domain. The effects of NMDAR2A and DRD2 polymorphisms are less
significant on P300 wave. However, time-frequency decomposition of
ERP data showed other effects could be observed in specific frequency
bands of all three polymorphisms that were not reflected in the timedomain
representation of the data. The results of this study show that
extended analyses on the correlations of genetic differences among
normal population on electrophysiological parameters may extend our
view on the genetic basis of cognitive activities.
P0975. GDAP1 gene mutation study among four Iranian families;
Axonal recessive Charcot-Marie-Tooth type 4 disease
M. Rostami 1 , M. Dehghan Manshadi 1 , T. Majidizadeh 1 , s. Seyedhasani 1 , r.
mirfakhraei 1 , M. Ebrahimi 2 , M. houshmand 1 ;
1 National Institute Center Genetics Engineering & Biotechnology, Tehran, Islamic
Republic of Iran, 2 special medical center, Tehran, Islamic Republic of Iran.
Autosomal recessive Charcot-Marie-Tooth (CMT) disease (CMT4) is a
complex group of severe childhood motor and sensory neuropathies,
characterized by an early age of onset with rapidly progressive distal
limb weakness and atrophy. CMT disease caused by mutations in
the ganglioside induced differentiation-associated protein 1 (GDAP1)
gene is a a severe autosomal recessive neuropathy originally reported
in families with either demyelinating CMT4A neuropathy or axonal neuropathy
with vocal cord paresis, which maps to the CMT4A locus on
chromosome 8q21.1
we studied four families with 5 affected patients. Significant evidence
for linkage was found for several markers from chromosome 8q
(D8S279, D8S551, D8S1474, D8S1289,
and D8S84).
Following an initial indication for linkage of the family to the CMT4A
locus on chromosome 8, we sequenced the Ganglioside-induced differentiation-associated
protein 1 (GDAP1) gene whose genomic structure
contains six exons, and identified mutation. We conclude that a
novel GDAP1 mutation is associated with AR-CMT.
P0976. Genome wide linkage of a large serbian family with
GEFS +
F. Annesi 1 , G. Provenzano 1 , S. Carrideo 1 , A. J. Ristic 2 , S. Jankovic 2 , G. Maksimovic
2 , B. Gnjatovic 2 , I. Petrovic 2 , N. Vojvodic 2 , D. Sokic 2 , A. Gambardella 1,3 , G.
Annesi 1 ;
1 National Research Council, Mangone (Cosenza), Italy, 2 Institute of Neurology,
Clinical Centre of Serbia, Belgrade, Serbia, 3 Institute of Neurology, University
Magna Graecia, Catanzaro, Italy.
Generalized epilepsy with febrile seizures plus (GEFS + ) is a familial
epilepsy syndrome characterized by heterogeneous phenotypes including
febrile seizures (FS), FS + in which children had seizures with
fever in early childhood that continued beyond age 6 years, or were associated
with afebrile tonic-clonic seizures, and FS + with other types of
generalized (absence, myoclonic, or atonic) or partial seizures. GEFS +
is an autosomal dominant disorder with incomplete penetrance. Mutations
in the SCN1B gene on 19q13 cause GEFS + type 1. Mutations in
the SCN1A gene on 2q24 cause GEFS + type 2. Mutations in the GA-
BRG2 gene on 5q31.1-q33.1 cause GEFS + type 3. GEFS + type 4 has
been mapped to chromosome 2p24. Mutations in the GABRD gene
can cause GEFS + type 5. Mutations in the SCN2A gene causes febrile
seizures associated with afebrile seizures. Recently, a novel FS locus
was reported on chromosome 21q22 in a family with 13 individuals
affected by FS and afebrile seizures. We identified a large multigenerational
GEFS + Serbian family with 20 affected individuals and we
performed genetic linkage analysis for exclusion of known candidate
genes and loci. Subsequently, we conducted a genome wide scan by
the Linkage Mapping set version 2.5 (Applied Biosystems) genotyping
382 microsatellite markers located at on average of 10cM distance
thoughout the genome. We used a dominant genetic model with 0.90
penetrance and a disease allele frequency of 0.001. Genome scan
revealed linkage at some chromosomal loci and analysis of implicated
regions is in progress.
2 0
P0977. Genetic polymorphisms in metabolizing genes and
susceptibility to childhood leukemia in the Russian population.
T. V. Nasedkina 1 , O. A. Gra 1 , O. V. Makarova 2 , Z. M. Kozhekbaeva 1 , A. S. Glotov
3 , E. V. Samochatova 2 ;
1 Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow,
Russian Federation, 2 Federal Clinical Research Center of Pediatric Oncology/Hematology,
Moscow, Russian Federation, 3 Ott’s Institute of Obstetrics and
Gynecology, Russian Academy of Medical Science, St.Petersburg, Russian
Federation.
Genetic polymorphisms in metabolizing genes have been reported to
be individually associated with increased susceptibility to childhood
leukemia. A case-control study including 332 patients with Acute Lymphoblastic
Leukemia (ALL), 71 patients with Acute myelogeneous leukemia
(AML) and 490 healthy individuals was conducted. All patients
were 0-18 years old, all controls were 18-34 years old and so failed the
possibility to develop childhood leukemia. The polymorphic variants of
genes CYP1A1 (4887C>A, 4889A>G, 6235T>C), CYP2D6 (1934G>A,
2637delA), GSTT1 (deletion), GSTM1 (deletion), MTHFR (677C>T,
1298A>C), MTRR (66A>G), NQO1 (609C>T), CYP2C9 (430C>T,
1075C>T), CYP2C19 (681G>A) and NAT2 (341T>C, 481C>T,
590G>A, 857G>A) have been studied using allele-specific hybridization
with Pharmagen-biochip (EIMB). We found that “rapid acetylator”
NAT2 genotype 341T/T,481C/C,590G/G, as well as combination of a
“rapid acetylator” NAT2 genotype with “null” GSTT1 genotype, “null”
GSTM1 genotype and double “null” GSTT1/GSTM1 genotype more
frequently occurred in patients than in population control and this difference
is statistically significant. Also polymorphic variant CYP1A1
*1/*2A was found to be more frequent among children with relapse
comparing with primary patients (OR = 2.11, p = 0.0291), while GSTT1
“null” genotype was less frequent among relapsed patients (OR = 0.55,
p = 0.0265). Our findings suggest that polymorphic variants of GSTT1,
GSTM1, NAT2 genes may consider as risk factors modulated the susceptibility
to leukemia among children in Russia, while polymorphic
variants of CYP1A1, NAT2, GSTT1, GSTM1 genes may have an impact
on clinical outcome.
The work was supported by the Basic Foundation for Russian Science
(project 06-04-49771)
P0978. Effect of 5HTT genetic polymorphism on agression in
atheletes
M. Timofeeva 1 , N. Maluchenko 1 , A. Tonevitsky 2 ;
1 Moscow State University, Moscow, Russian Federation, 2 Russian Research
Institute of Sport and Physical Education, Moscow, Russian Federation.
Genetic variations of serotonin transporter gene (5HTT) are closely related
with human adaptive ability to control emotion and very attractive
in investigation of athletes whose life is accompanied by high emotional
pressure. Present study investigated the effect of genetic polymorphism
of 5HTT on aggression of athletes, 86 synchronized swimmers
and 83 non-trained female controls were genotyped. 73 (age 8-18)
of synchronized swimmers are actively engaged in competition, 64 of
them participated in psychological testing of aggression (Buss-Durkee
Hostility Inventory). Analysis of primary of this test reveals, that Indirect
Hostility is increased with both short alleles SS compared with other
groups (SL and LL).
Furthermore, it was shown that the frequency of 5HTT alleles in groups
of elite athletes of different kind of specialization are differ between
kind of sport and between athletes and control group. Interrelation of
5HTT genotype, aggressiveness and athletic successfulness are vigorously
discussed.
P0979. Genome-wide association mapping of the QT-interval in a
500k scan: confirmation of the NOS1AP locus and identification
of a spectrum of additional QTLs
A. Pfeufer1 , M. Akyol1 , M. F. Sinner2 , S. Perz3 , C. Gieger3 , B. M. Beckmann2 , M.
Hinterseer2 , H. Prucha2 , T. Illig3 , H. E. Wichmann3 , S. Kääb2 , T. Meitinger1 ;
1 2 3 TU Munich, Munich, Germany, LMU Munich, Munich, Germany, GSF National
Research Center, Neuherberg, Germany.
Background: The electrocardiographic QT-interval is a normally distributed
quantitative trait in the general population with over 30% heritability,
which is associated with sudden cardiac death. In a previous100k
scan we have identified a QTL for QT-interval at the NOS1AP gene
which explained approximately 1,5% of trait variance.
Aim: To comprehensively map the spectrum of QTLs we now under-