2008 Barcelona - European Society of Human Genetics

Normal variation, population genetics, genetic epidemiology
P07.111
Analysis of Polymorphism of the cAG Repeats in the
spinocerebellar Ataxia type 1 (scA1) Gene in Human
Populations of the Volga-Ural Region
E. Mingazova, E. Khusnutdinova, I. Khidiyatova;
Institute of Biochemistry and Genetics, Ufa, Russian Federation.
Spinocerebellar Ataxia type 1(SCA1) is a neurodegenerative disease,
is characteristic at the molecular level by CAG repeat expansions on
6p23 in the SCA1 gene . Distribution of normal alleles of CAG repeats
in SCA1 gene was analyzed in populations of the Volga-Ural region,
including Tatars, Russians, Maris, Udmurts, Komis, Chuvashes, three
ethnogeographical groups of Bashkirs and two ethnogeographical
groups of Mordovians . 13 alleles (8-12 in different populations), containing
24-37 trinucleotide repeats were found as a result of 956 DNA
samples analysis . The allele frequency distribution showed two the
most frequent alleles corresponding to 31CAG repeats with the frequency
varied from 0,161 in Tatars to 0,328 in Chuvashes, and 32CAG
repeats - from 0,152 in Mordovians erza to 0,425 in Chuvashes . Allele
with large number of repeats (CAG) 37 was found in Bashkirs from
the Abzelilovskii, Burzanskii regions, Mordovians erza with frequency
of 0,008, 0,005, 0,022 . Transitional alleles with number of repeats
(CAG) 37-39 are unstable triplet repeats and can given subsequent mutation.
Allele frequency distribution of SCA1 gene is significantly heterogeneity
. The observed heterozygosity was the highest (99%) in Bashkirs
from the Abzelilovskii region and the lowest (44%) in Mordovians
erza; the average heterozygosity was 73,6%, and allows to consider
this polymorphic DNA locus to be a highly informative genetic marker
for populations . At present in the Bashkortostan Republic (Russia,
South Ural, population 4069784 people) 10 families with progressive
autosomal-dominant spinocerebellar ataxias were revealed, and in 2
of the examined families revealed the expansion of (CAG)n-repeats in
SCA1 gene .
P07.112
DNA copy number analysis in a case-control study of
schizophrenia
F. Torri 1 , S. Lupoli 2 , S. Potkin 3 , E. Salvi 1 , J. Turner 3 , G. Guffanti 1 , A. Orro 4 , J.
Fallon 3 , C. Barlassina 1 , D. Cusi 1 , F. Macciardi 1 ;
1 University of Milan, Milan, Italy, 2 INSPE, Milan, Italy, 3 Dept. of Psychiatry &
Neuroscience, UCI, Irvine, CA, United States, 4 CILEA, Segrate, Milan, Italy.
Recent studies have highlighted DNA copy-number variations (CNVs)
as a largely under-explored source of human genetic variation, which
could be responsible for the development of complex disorders . According
to this hypothesis, evaluation of DNA copy number in schizophrenia
may yield insights into the discovery of genetic risk factors for
this disease (as aberrations in genes involved in glutamate signalling
suggested in a recent report1), as CNVs can also be transmitted as
mendelian traits2 .
We have assayed 317 .511 SNPs in 172 DNA samples from a casecontrol
study of schizophrenia, including 91 controls and 82 schizophrenics,
representing the first wave of a much larger sample, using
the Illumina HumanHap300 Genotyping BeadChip® . In an effort to
examine individual chromosomes for structural mutation, we used two
different classes of algorithm: cnvPartition (circular binary segmentation
algorithm) implemented in BeadStudio v3 .0 .22 and quantiSNP3
(Objective Bayes Hidden Markov Model) .
Statistical analyses performed on genotyping data-sets of our study
revealed that the overall distribution of CNV assignments is significantly
different between schizophrenic patients and controls, with the
main difference observed for duplications, which are more frequent in
schizophrenics than in controls .
REFERENCES:
1 .Wilson et al .,Hum . Mol . Gen . 15, 743-749, 2006
2 . Sebat J . et al ., Science 316, 445-49, 2007
3 . Colella S . et al ., Nucleic Acids Research 1-13, 2007
P07.113
Analysis of Y-chromosomal stR haplotypes in two ethnic
groups and one cosmopolitan population from tunisia
K. Fadhlaoui-Zid 1 , I. Mendizabal 2 , H. Khodjet Ell Khill 1 , B. Martinez-Cruz 2 , M.
Ben Amor 1 , A. Ben Ammar Elgaaeid 1 , D. Comas 2 ;
1 Laboratoire de Génétique, Immunologie et Pathologies humaines. Faculté
des Sciences de Tunis. Université Tunis El Manar, Tunis, Tunisia, 2 Unitat de
Biologia Evolutiva. Universitat Pompeu Fabra. Doctor Aiguader 88, 08003,
Barcelona, Spain.
Human Y-chromosome short tandem repeat (Y-STR) markers show
a high level of polymorphism and a significant degree of discrimination
between individuals . Analysis of human Y-STR polymorphism has
become a very useful tool both in evolutionary studies and in forensic
casework, due in part to the loci being recombination free during meiosis
and paternally inheritance. In order to define the Y-chromosome
genetic structure in Tunisian population, 17 Y-STRs were typed in
159 unrelated healthy males in two ethnic groups (‘‘Andalusians’’ and
Berber) and one cosmopolitan population (Tunis) from Tunisia, using
AmpFLSTR® Yfiler PCR Amplification Kit (AB Applied Biosystems).
Allele and haplotype frequencies, standard diversity indices, pairwise
genetic distances (RST) and analysis of molecular variance (AMO-
VA) were calculated with the software Arlequin version 2 .000 . A total
number of 111 haplotypes were identified by the 17 Y-STR loci in our
study sample and 91 haplotypes were unique . All the groups analysed
showed high haplotype diversities, the highest value being observed
in the ‘‘Andalusians’’ sample: 0 .9924 +/- 0 .0104 for ‘‘Cosmopolitan’’;
0 .9765 +/- 0 .0132 for Berbers from Sened; 0 .9886 +/- 0 .0131 for Berbers
from Chenini-Douiret; 0 .8367 +/- 0 .0547 for Berbers from Jeradou
and 0 .9940 +/- 0 .0095 for Andalusians . The highest diversity revealed
for Chenini-Douiret using this Y-STR is not expected, as compared to
mtDNA or autosomic markers analysis . The hierarchical analysis of
variance carried out between the Berber and Arabic-speaking groups
failed to demonstrate any significant differentiation between them.
These results corroborate the absence of overall genetic differentiation
between Berbers and Arabs in Tunisia .
P07.114
Population data on the X chromosome short tandem repeat loci
DXs9895, GAtA172D05, DXs6810, DXs6803 and HPRt in croatia
K. Crkvenac Gornik 1 , K. Štingl 2 , Z. Grubić 2 , I. Tonković Đurišević 1 , L. Letica 1 , M.
Burek 1 , R. Lasan 1 , D. Mužinić 1 , D. Begović 1 ;
1 Division of Metabolic and Genetic Diseases, Clinic of Pediatrics, University
Hospital Centre Zagreb, Croatia, Zagreb, Croatia, 2 Tissue Typing Centre, University
Hospital Centre Zagreb, Zagreb, Croatia.
Due to its high polymorphism, the analysis of Short Tandem Repeat
(STR) markers using the PCR method has become a widely applied
technique in forensic individual identification, rapid detection of chromosome
aneuploidies in prenatal and postnatal diagnosis and paternity
testing . Until now a large number of autosomal and Y-chromosomal
markers has been forensically evaluated and used for various purposes,
but the application of X-chromosomal markers has played only a
minor role in forensic practice so far . The X-STR loci (DXS9895, GA-
TA172D05, DXS6810, DXS6803 and HPRT) were investigated in male
(N=90) and female (N=93) population samples from Croatia . Samples
were collected from randomly selected unrelated healthy individuals .
No deviation from the Hardy-Weinberg equilibrium could be detected
and allele frequencies showed similar distribution in male and female
samples . With the exception of DXS6810 locus for which only 6 alleles
were observed and PIC value lover than 0 .75 was calculated, all other
loci have demonstrated sufficient polymorphism and PIC value to be
considered valuable in future forensic analyses .
P07.115
Epidemiology of monogenic hereditary skeletal diseases in
Rostov region of Russian Federation
R. A. Valkov 1 , T. I. Valkova 2 , S. S. Amelina 2 , R. A. Zinchenko 3 ;
1 Railroad clinical hospital, Rostov-on-Don, Russian Federation, 2 Rostov regional
clinical hospital, Rostov-on-Don, Russian Federation, 3 Research Center
for Medical Genetics, Moscow, Russian Federation.
Monogenic hereditary skeletal diseases have many various clinical
forms and characterized by genetic heterogeneity . The main purpose
of our research was determination of hereditary factor’s role in common
structure of skeletal diseases, and theirs prevalence at population
of Rostov region of Russian Federation . 320925 people of eight
area of Rostov region were examining . All hereditary skeletal diseases
were dividing into isolated and syndromic forms . In the results 336
patients of 226 families are had hereditary skeletal diseases . It was
36% of all patients with hereditary diseases . The total prevalence rate
of hereditary skeletal diseases in Rostov region was 1:950 persons . At
that, the prevalence rate of isolated forms was 1:2700, and syndromic