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

Normal variation, population genetics, genetic epidemiology
Thailand.
Background: While there are strong genetic evidences linking the
population in the Indochina peninsula with the Chinese, this was not
the case with the Indians despite the proximity of the region to both
populations. Using the heterogeneity of the spinocerebellar ataxias,
a group of neurological disorders with different subtype frequencies
among different populations, we looked for the evidence supporting
relationship between the Thai population and both the Chinese and
Indian populations.
Methods: We searched for spinocerebellar ataxia (SCA) type 1, SCA3
and SCA6 mutations in 340 patients from 182 families, in which at least
one person had a clinical diagnosis of SCA, using GeneScan analysis.
We analysed the relative frequencies of SCAs subtypes on a family
basis, and compared these to the data in the related populations.
Results: SCA3 was the commonest, with a relative frequency of 17.0%
(Agresti-Coull 95% C.I.: 12.2%-23.2%), followed by SCA1 at 10.4%
(6.7%-15.8%). SCA6 was found in three families, with a relative frequency
of 1.6% (0.3%-5.0%). When compared to the related populations,
the Thai SCA3 frequency was less than that of the Chinese while
higher than that in most of the Indian studies. The reverse is true for
the SCA1. A similar study in Singapore, where the pattern of population
admixture was clear, also showed somewhat similar results, although
more inclined toward the Indians.
Conclusion: Our results supported some degree of admixture with the
Indians in Thai population, and should encourage further study in the
area.
P1218. Population study at fifteen short tandem repeat loci in
the representative sample of Bosnia and Herzegovina residents
- contemporary data
D. Marjanovic 1,2 , A. Durmic-Pasic 1 , N. Pjanic 1 , N. Bakal 1 , L. Kovacevic 1 , V.
Skaro 2 , P. Projic 2 , S. Haveric 1 , K. Bajrovic 1 , R. Hadziselimovic 1 , D. Primorac 3 ,
N. Pojskic 1 ;
1 Institute for Genetic Engineering and Biotechnology, Sarajevo, Bosnia and
Herzegovina, 2 Center for Integrative Genomics, Molecular Diagnostics, Cell and
Gene Therapy, “Rudjer Boskovic” Institute, Zagreb, Croatia, 3 Medical School at
Osijek University, Osijek, Croatia.
In our previous population studies of B&H human population, we used
17 autosomal and 12 Y-chromosomal STR loci, as well as 28 NRY
bi-allelic markers to generate referent database. Wishing to test our
database in order to obtain specific results in various DNA analysis, we
have decided to analysis additional individuals, firstly at fifteen autosomal
STR loci (D3S1358, TH01, D21S11, D18S51, Penta E, D5S818,
D13S317, D7S820, D16S539, CSF1PO, Penta D, vWA, D8S1179,
TPOX, FGA). Therefore, we have tested additional group of 100 unrelated
healthy individuals born in B&H. Qiagen Dnaeasy TM Tissue Kit
was used for DNA extraction from buccal swabs and bloodstains and
PowerPlex 16 ® System for amplification and detection. The total volume
of PCR reaction was 5μl and PCR amplifications were carried
out in PE GeneAmp PCR System Thermal Cycler. Electrophoresis of
the amplification products was preformed on an ABI PRISM 310 genetic
analyzer. The raw data were compiled and analyzed using Genemapper
® v3.2. Deviation from Hardy-Weinberg equilibrium, observed
and expected heterozygosity, power of discrimination and power of
exclusion were calculated. Statistical differences between the new
set of data and the data at same loci published earlier (based on 100
tested individuals) indicated the advantage of using recently obtained
frequencies, especially as it pertains to the forensic-genetic statistical
analysis. In addition, we compared B&H data with the data obtained
from geographically closer European populations. The results of this
study will be used as guidelines in additional improving of investigation
of recent B&H human populations, initiated in our previous studies.
P1219. Possible common origin for the Tibeto-Burman and
Austro-Asiatic speaking populations of India: a Y-chromosome
study
S. Krithika 1 , A. Singh 2 , S. Sahoo 2 , R. Trivedi 2 , V. K. Kashyap 3 , T. S. Vasulu 1 ;
1 Indian Statistical Institute, Kolkata, India, 2 National DNA Analysis Centre,
Central Forensic Science Laboratory, Kolkata, India, 3 National Institute of Biologicals,
Noida, India.
The geographic contiguity and the morphological similarity of the Tibeto-Burman
speaking populations with the Austro-Asiatic speaking
groups of India provide hints for the origin of the two linguistic families
from a common stock in the remote past. However, this intriguing aspect
of genetic relationship between the Tibeto-Burman and Austro-
Asiatic speaking populations of India is little investigated and warrants
further discussion through molecular genetics.
In this regard, we analyzed 38 biallelic and 20 short tandem repeat
polymorphisms on the Y-chromosome in 293 male individuals of 22
different populations belonging to Tibeto-Burman (12) and Austro-
Asiatic (10) linguistic families, inhabiting northeastern, eastern and
central regions. Among the 14 haplogroups observed, subclades of
haplogroup O were predominant (~83.96%) of which O2a, showing the
highest frequency of ~ 55%, was the major common subclade present
in both Tibeto-Burman (41.3%) and in Austro-Asiatic (73%) populations.
AMOVA results indicated a higher degree of genetic differentiation
(31.95%) among populations within the two linguistic groups than
among the two groups (13.10%). The neighbor-joining tree and the
PCA plot shows clustering of some Austro-Asiatic populations (mainly
from Jharkhand) with few Tibeto- Burman populations from Arunachal
Pradesh and Mizoram suggesting possible shared common ancestry
of some Tibeto-Burman with a few of the Austro-Asiatic populations.
STRUCTURE analysis is also in congruence with the genetic commonality
between the studied linguistic groups. To get further insight
into the issue, a median-joining network was constructed based on the
haplotypes that fall into haplogroup O2a and the time of divergence for
the haplogroup was also estimated.
P1220. Thiopurine S-methyltransferase (TPMT)
pharmacogenetics: genotype-phenotype comparison and
haplotype analysis in Estonian population
R. Tamm1 , K. Oselin2 , K. Kallassalu1 , K. Anier2 , R. Magi1 , A. Metspalu3 ;
1 2 IMCB, Tartu, Estonia, Department of Pharmacology, Tartu, Estonia,
3IMCB,EBC, Tartu, Estonia.
Thiopurine methyltrasferase (TPMT) is a cytoplasmic enzyme catalysing
the S - methylation of thiopurine drugs. Thiopurines exert cytotoxicity
after metabolism to thioguanine nucleotides and they are turned
into inactive metabolites by TPMT. To date, at least 23 single nucleotide
polymorphisms/mutations have been reported in TPMT gene, 22
of them are or may be associated with low enzyme activity.
The aim of the present study was to measure erythrocyte TPMT activity
in Estonian population, to genotype Estonian population using
PCR-RFLP method for known alleles (TPMT*2, *3A, *3B, *3C, *3D,
*8) and to sequence the whole coding region of TPMT (exons 3-10)
to find novel sequence variants. Of 253 healthy subjects, 15 were heterozygous
for TPMT*1/*3A (3%), two for TPMT*1/*3C (0.4%) and two
for TPMT*1/*2 (0.4%). No subjects were detected with TPMT*3B, *3D
and *8. Several others previously described intronic and exon mutations/polymorphisms
were found via sequencing. Three novel mutations
T30A in exon 3, A10G in intron 3 and A145G in intron 10 were
detected. Association and haplotype analysis was carried out to find
SNP differences between low (enzyme activity £58.8 ng/ml/h), intermediate
and high (enzyme activity ³130 ng/ml/h) metabolizers. Four
SNPs were present together (T114A, T94A, G460A, A719G) and were
more significantly (P < 0.001) represented in low metabolizers compared
to intermediate and high ones.
According to our study several markers predict low enzyme activity, but
any specific markers were not correlated with high enzyme activity.
P1221. Analysis of three Microsatellite Markers (vWA31A,
CSF1PO and TPOX) of two Romanian population groups and
their genetic relationships to European populations
A. Rodewald 1 , A. Kroll 1 , S. Mueler-Scholtz 1 , A. Lungeanu 2 , G. Cardos 2,3 , D.
Banica 4 ;
1 Department of Human Biology, Univ. Hamburg, Hamburg, Germany, 2 ”Victor
Babes” National Institute, Bucharest, Romania, 3 Faculty of Biology, University
of Bucharest, Bucharest, Romania, 4 ”Marius Nasta” Institute of Pulmonary Diseases,
Bucharest, Romania.
In this research 3 different DNA-polymorphisms (Microsatellites:
vWA31A, CSF1PO and TPOX) have been detected and analysed in a
sample of 110 individuals from Prahova Valley (Carpathian Mountains)
as well as in a sample of 200 individuals from the Romanian capital,
Bucharest. Further, we investigated the extent of genetic influences of
European neighbour populations on the Romanian genetic pool.
The results reveal that there were not any significant differences in
the allele frequencies in the three Microsatellite markers from the pan-
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