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

Genetic analysis, linkage, and association
bours several genes that have an immunological function, and which
could therefore have a putative role in celiac disease.
41 single-nucleotide polymorphisms that tag 17 immunologically relevant
genes in a region spanning nearly 20 Mb (130.7-150.0 Mb) at
the CELIAC2 locus were selected for this study. They were genotyped
in a total of 541 Hungarian and Finnish affected sib-pair and trio pedigrees.
The analysed region showed linkage to celiac disease in the combined
Finnish and Hungarian material (p=0.0015) and in the Finnish
population alone (p=0.004). Borderline significant linkage values were
observed in the Hungarian population (p=0.03). Several genes and
haplotype blocks showed suggestive association with celiac disease.
More finemapping will be needed to identify the gene or genes possibly
associated with celiac disease in the region. Functional studies of
the associated genes will also be required to confirm their role in the
pathogenesis of celiac disease.
P0925. Gene expression variability of immunologicaly important
genes in blood and intestine of celiac patients: a comparative
study
S. Adamovic 1 , E. Hanson 1 , A. Gudjόnsdόttir 2 , H. Ascher 3 , S. Nilsson 4,5 , J. Wahlström
1 , Å. Torinsson Naluai 1,6 ;
1 Institution of Biomedicin, Göteborg, Sweden, 2 Department of Paediatrics,
The Queen Silvia Children’s Hospital, Sahlgrenska University Hospital / Östra,
Göteborg, Sweden, 3 The Nordic School of Public Health, Göteborg, Sweden,
4 Chalmers University of Technolog, Göteborg, Sweden, 5 Bioinformatics Core
Facility, Göteborg, Sweden, 6 Genomics Core Facility, Göteborg, Sweden.
Is it possible to estimate the extent of inflammation in the intestine
of a celiac patient by monitoring changes in gene expression in the
peripheral blood? We are trying to find an answer to that question by
comparing the expression of 94 relevant immune genes between inflamed
tissue and blood in two celiac cases and two controls. Among
genes we are testing there are cytokines, chemokines, growth factors,
immune regulators, apoptosis markers, ischemia markers, tissue-specific
markers, and other genes taking part in immunological responses.
For this purpose we are using pre-designed Low Density Arrays based
on TaqMan® technology. Blood samples and biopsies from the duodenum
and small intestine are taken at the same occasion in all individuals.Our
preliminary results are showing that a number of genes
expressed in the intestine are not measurable in blood. On the other
hand, the altered expression of several genes in the intestine corresponds
to an altered expression of the same genes in the peripheral
blood, which makes them potential markers for inflammation. Our aim
is to investigate if some of those genes may co-act in a distinct inflammatory
pathways and whether measuring expression of one gene can
predict the expression level of other genes. Moreover, we are trying to
establish a method to correlate changes in gene expression in peripheral
blood to a level of intestinal damage in celiac cases.
P0926. Demyelinating Autosomal Recessive Charcot-Marie-
Tooth disease (ARCMT1): Estimation of loci frequencies in 34
consanguineous families originated from the Mediterranean
basin and middle Est
C. Verny 1,2 , H. Azzedine 1,2 , E. Mikesova 1 , A. Thiam 3 , P. Latour 4 , M. A. M. Salih 5 ,
M. Tazir 6 , M. Hamri 7 , M. Sifi 7 , N. Birouk 8 , N. Ravise 1 , M. Mayer 9 , O. Dubourg 1,10 ,
A. Brice 1,11 , E. Leguern 1,11 ;
1 INSERM, U679, Paris, France, 2 INSERM, U694, Angers, France, 3 Service de
Neurologie, CHU de Dakar, Dakar, Senegal, 4 Laboratoire de Biochimie Pediatrique,
Hopital Debrousse, Lyon, France, 5 Department of Paediatrics College
of Medecine, Ryadh, Saudi Arabia, 6 CHU Mustapha, service de neurologie,
Algiers, Algeria, 7 Service de Neurologie, CHU de Canstantine, Canstantine,
Algeria, 8 Service de neurophysiologie, Hôpital des spécialités, Rabat, Morocco,
9 Service de Neuropédiatrie, Hôpital Trousseau, Paris, France, 10 Laboratory of
Neuropathology, Escourolle, La pitié-Salpêtrière Hospital, Paris, France, 11 Laboratory
of neurogenetics, Department of Genetics, Cytogenetics and Enmbryology,
la Pitié-Salpêtrière Hospital, Paris, France.
CMT is a pathological and genetic heterogeneous group of hereditary
motor and sensory neuropathies. Two major types have been
distinguished on neuropathological and electrophysiological grounds:
demyelinating and axonal CMT. Nine loci have been reported and 7
genes identified in demyelinating ARCMT. We selected 34 consanguineous
families in whom 62 subjects presented ARCMT1 in a total
of 156 individuals. These families are originated from the Mediterra-
nean basin and middle Est. All the individuals were screened for 54
microsatellites markers covering the 9 known loci. PCR products were
resolved in an ABI-Prism 3100 automated sequencer and analyzed
with Genescan and Genotyper software (ABI TM ). Assignment of the
families to each locus was established by homozygocity mapping and
linkage analysis using Allegro1.2. When a linkage was suspected the
coding sequences of the corresponding gene were sequenced. The
fragments were analyzed with sequencing analysis and SeqScape
software (ABI). We identified 14 families (41%) with linkage to one
of the known loci. CMT4B1 (MTMR2) and CMT4C (SH3TC2) are the
most frequent (14.9% each). They represent about 30% of the known
loci, in our series and are found in families originated from Algeria,
Bosnia, France, Morocco, and Saudi Arabia. CMT4D (NDRG1) is less
frequent (5.9%). CMT4A (GDAP1) represents 2.8% of the known loci.
CMT4A and 4D were found only in Italian families. CMT4B2 (MTMR13)
and CMT4F (PRX) were suspected in one Tunisian family (2.8%). Sequencing
of the corresponding genes is in progress. 59% of families
were not associated with the known loci, demonstrating further genetic
heterogeneity.
P0927. A molecular genetic study of Charcot-Marie-Tooth Type 1
in Turkey
E. Battaloglu 1 , B. Bilir 1 , I. Baris 1 , B. Senergin 1 , I. Akat 1 , O. N. Maracı 1 , Y. Parman
2 ;
1 Bogazici University, Istanbul, Turkey, 2 Istanbul University, Istanbul, Turkey.
Charcot-Marie-Tooth Type 1 (CMT1) is a genetically heterogeneous
neuropathy that is associated with PNS demyelination. It is characterized
with reduced NCV values (