2009 Vienna - European Society of Human Genetics

Evolutionary and population genetics, and Genetic epidemiology
P10.73
Genetic disorders in saudi Arabia- An update
A. S. Warsy1 , M. A. F. El-Hazmi2 ;
1Department of Biochemistry, College of Science, Center for Science and Medical
Studies for Girls, King Saud University, Riyadh, Saudi Arabia, 2Department of Biochemistry, College of Medicine, King Saud University, Riyadh, Saudi
Arabia.
Saudi Arabia, is the largest Arab country and has an estimated population
of around 27.6 million. The family and tribe are the basis of the social
structure and Saudis are cognizant of their heritage, their tribe, and
their extended and nuclear family. Consanguinity and other factors,
including environmental factors, have played a significant role in accumulating
genetic disorders, some very rare ones, at a higher frequency
in the Saudis. We conducted three National studies over a period of
twenty years to screen the entire country for common single gene disorders
(including sickle cell gene, α- and β- thalassaemia, glucose-
6-phosphate dehydrogenase deficiency) and multifactorial disorders
(including diabetes mellitus, obesity, and hypertension). Over 60,000
samples were screened and gene frequencies of these disorders were
obtained. In addition, studies conducted in other institutions reported
several inborn errors of metabolism, chromosomal, mitochondrial and
somatic cell disorders (cancers). Several disorders, rare in other populations,
occur at a high frequency in the Saudi. The genetic basis of
several of these disorders has been unveiled and very interesting picture
has emerged for the common disorders, where mutations specific
to Saudis and rare in other populations form the basis of several of
the common disorders. The natural history of several of the disorders
has been investigated and a wide range of clinical diversity has been
identified. Steps have been adopted towards primary prevention. This
paper will present a comprehensive coverage of the present status of
genetic diseases in Saudi Arabia and steps adopted towards control
and prevention.
P10.74
Ancestral origin of pure repeat expansions and cAA interrupted
alleles in spinocerebellar ataxia type 2 (scA2)
E. M. Ramos 1 , S. Martins 1,2 , I. Alonso 1 , V. E. Emmel 3 , M. L. Saraiva-Pereira 3 , L.
B. Jardim 3 , P. Coutinho 1,4 , J. Sequeiros 1,5 , I. Silveira 1 ;
1 UnIGENe, IBMC - Instituto de Biologia Molecular e Celular, Porto, Portugal,
2 IPATIMUP- Instituto de Patologia e Imunologia Molecular da Universidade
do Porto, Porto, Portugal, 3 Hospital de Clínicas de Porto Alegre, Porto Alegre,
Brazil, 4 Hospital São Sebastião, Feira, Portugal, 5 ICBAS, Universidade do
Porto, Porto, Portugal.
The spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant
neurodegenerative disease characterized by gait and limb ataxia.
This disease is caused by the expansion of a (CAG)n located in the
ATXN2, that encodes a polyglutamine tract of more than 34 repeats.
Lately, alleles with 32-33 CAGs have been associated to late-onset
disease cases. Repeat interruptions by CAA triplets are common in
normal alleles, while expanded alleles usually contain a pure repeat
tract. To investigate the mutational origin and the instability associated
to the ATXN2 repeat, we performed an extensive haplotype study and
sequencing of the CAG/CAA repeat, in a cohort of families of different
geographic origins and phenotypes. Our results showed (1) CAA
interruptions in ATXN2 alleles, regardless of its pathogenic nature,
and that (2) CAA interrupted alleles in the range 33-44 repeats shared
an ancestral haplotype with pure expanded alleles; (3) an intragenic
SNP-based haplotype, C-C, common to all SCA2 families regardless
of its interruption pattern, origin or phenotype; and (4) higher genetic
diversity in European SCA2 families, suggesting an older European
ancestry of SCA2. In conclusion, we found a shared ancestral ATXN2
haplotype for pure and interrupted expanded alleles, with strong implications
in mutation diagnosis and counseling. Our results indicate that
interrupted alleles, below the pathological threshold, may be a reservoir
of mutable alleles, prone to expansion in subsequent generations,
leading to full disease mutation
P10.75
Allele frequencies of eight short tandem repeat loci in East
Azerbaijan province population
J. Mohseni 1 , S. Mohaddes Ardebili 2 , H. Najm-Aabadi 3 ;
1 East azerbaijan brach of ACECR, Tabriz, Islamic Republic of Iran, 2 Tabriz
medical sciences university, Tabriz, Islamic Republic of Iran, 3 Welfare and Re-
habilitaion university, Tehran, Islamic Republic of Iran.
Short tandem repeats (2-6 bp) have become wide-spread in their
use by the forensic DNA typing, Paternity testing, gene mapping,
and diagnosis of hereditary disease. Allele frequencies for 8 STR loci
(D16S539, D8S1179, D5S818, D13S317, F13B, MTHO1, TPOX and
FES/FPS) were determined in the samples of 218 un-related volunteer
of East Azerbaijan province population using PCR and subsequent
poly-acrylamid gel electrophoresis and silver staining.
Regarding to the results, Among 8 STR loci , heterozygosity of
D16S539, D5S818,D8S1179, D13S317, F13B, FES/FPS,MTHO1,
TPOX respectively were 0.8213,0.8188, 0.7883, 0.8062, 0.7442,
0.7397, 0.7834, 0.6769 . No devotion from Hardi-winberg equilibrium
was observed. D16S539 with 0.8213 heterozygosity is the most informative
marker and TPOX with 0.6769 heterozygosity was the least informative
marker on target group. Therefore except for TPOx all mentioned
markers could be used for forensic DNA typing and paternity
test of East Azerbaijan population.
P10.76
Forensic value of 10 stR loci in the entire region of turkey
population and comparisons to other ethnics groups or areas
M. Ozkorkmaz 1 , A. Baransel-Isir 2 , S. Pehlivan 3 , E. Gokalp-Ozkorkmaz 4 ;
1 Ege University Faculty of Science, Izmir, Turkey, 2 2. Gaziantep University, Faculty
of Medicine, Department of Forensic Medicine, Gaziantep, Turkey, 3 4. Gaziantep
University, Faculty of Medicine Department of Medical Biology and Genetic,
Gaziantep, Turkey, 4 Ahi Evran University, College of Healty, Kırsehir, Turkey.
Allele frequencies of the 10 STRs loci (D16S539, D2S1338, D3S1358,
vWA, D18S51, D21S11, D8S1179, D19S433, FGA, THO1) included
in the AmpFlSTR SGM Plus kit were obtained from different biological
materials of sample of 100 unrelated individuals in the entire region of
Turkey. Chi-square test showed that all STR loci agreed with Hardy-
Weinberg equilibrium. The population genetic data were compared
with the previously publishing population data of Turkish and other
ethnic groups or areas. The results of present study suggest that 10
STR loci with its high combined PD values (0.99999999999988) seem
to be a useful system for the cases in forensic identifications.
P10.77
Estimation of smN1 Deletion carrier Frequency in the iranian
Population based on Quantitative Analysis
M. Hasanzad 1 , M. Azad 2 , K. Kahrizi 3 , B. Shoja Saffar 3 , S. Nafisi 4 , Z. Keyhanidoust
5 , M. Azimian 3 , A. Aghajani Refah 3 , E. Also 6 , J. A. Urtizberea 7 , E. F. Tizzano
6 , H. Najmabadi 3,2 ;
1 Islamic Azad University, Tehran Medical Branch, Tehran, Islamic Republic of
Iran, 2 Kariminejad-Najmabadi Pathology & Genetics Center, Tehran, Islamic
Republic of Iran, 3 Genetics Research Center, University of Social Welfare
& Rehabilitation Sciences, Tehran, Islamic Republic of Iran, 4 Department of
Neurology, Tehran University of Medical Sciences, Tehran, Islamic Republic
of Iran, 5 Imam Khomeini Hospital, Tehran University of Medical Sciences,
Tehran, Islamic Republic of Iran, 6 Department of Genetics, Hospital de Sant
Pau, Barcelona, Spain, 7 Assistance Publique Hopitaux de Paris, Hopital Marin,
Hendaye, France.
Spinal muscular atrophy (SMA) is a common autosomal recessive neuromuscular
disorder caused by mutations in the survival motor neuron
1 gene (SMN1). Carrier frequency studies of SMA have been reported
for various populations. Although no large-scale population-based
studies of SMA have been performed in Iran, previous estimates have
indicated that the incidence of autosomal recessive disorder partly because
of the high prevalence of consanguineous marriage is much
higher in the Iranian population than in other populations.
In this study, we used a reliable and highly sensitive quantitative realtime
PCR assay with SYBR green I dye to detect the copy number
of the SMN1 gene to determine the carrier frequency of SMA in 200
healthy unrelated, non consanguineous couples from different part of
Iran
To validate the method in our samples, we determined the ΔΔCt ratios
of patients with homozygous deletion (0.00) and hemyzygous carriers
(0.29 to 0.55). The ΔΔCt ratios in 10 of 200 normal individuals were
within the carrier range of 0.31-0.57, estimating a carrier frequency of
5% in the Iranian population.
Our data show that the SMA carrier frequency in Iran is higher than in
the European population and that further programs of population carrier
detection and prenatal testing should be implemented.