2008 Barcelona - European Society of Human Genetics

Normal variation, population genetics, genetic epidemiology
distance runners, swimmers and skaters, road cyclists, skiers, triathletes,
race walkers) and 1197 controls . Genotyping was performed by
restriction fragment length polymorphism analysis . The distribution of
ACTN3 genotypes (athletes: RR - 37 .1%, RX - 53 .1%, XX - 9 .8%;
controls: RR - 36.8%, RX - 49.0%, XX - 14.2%) was significantly different
between athletes and controls (P=0 .038) . While R allele frequency
did not differ between athletes (63 .7%) and controls (61 .3%), the frequency
of XX genotype was under-represented in athletes compared
to controls (9 .8% vs . 14 .2%, P=0 .013) . We therefore conclude that XX
genotype is unfavorable for endurance performance .
P07.004
Analisis of IGF- gene and PGC- gene polymorphism in
newborn and elderly people from North-west region of Russia
S. V. Potulova 1 , O. S. Glotov 2 , V. S. Baranov 2 ;
1 Saint-Petersburg State University, St-Petersburg, Russian Federation, 2 Ott
Institute of Obstetrics and Gynecology, St-Petersburg, Russian Federation.
Our goal was to investigate whether a polymorphism in the insulin-like
growth factor I promoter gene (IGF-1, wild-type, 192 base pairs) and
in the peroxisome proliferator activated receptor coactivator-1 gene
(PGC-1, Gly482Ser polymorphism) influence life expectancy.
Different distribution of IGF-1 (CA repeats) gene polymorphism was
shown . Increasing of 20/- genotype in elderly people compared with
newborn group (26.7%and 44.1%, accordantly, χ2=8.57, p=0.0034)
and decreasing of 19/19 genotype (51% and 27 .9%, accordantly,
χ2=14.815, p=0.0001) were founded. Furthermore, it was shown different
distribution of IGF-1 (CA repeats) gene polymorphism in man
and woman . Increasing of 19/20 genotype in newborn man compared
with newborn woman (23 .2% and 11 .3%, accordantly) as well as significant
increasing of 19/20 genotype in elderly man compared with
elderly woman (44.4% and 21.1%, accordantly, χ2=5.009, p=0.025)
was detected . We suggest a possible role of IGF-1 gene CA- polymorphism
in ageing .
The prevalent Gly482Ser polymorphism of the PGC-1 gene has not
been shown to be associated with life expectancy . Increase of Gly/
Gly genotype in elderly woman compared with elderly man (51 .0% è
27.3%, accordantly, χ2=4.063, p=0.0438) was registered. Analysis of
joint contribution of both genes in ageing revealed the significant difference
between groups of newborn and elderly people (20%, 41 .8%,
accordantly, χ 2 =4 .858, p=0 .0275) . We suggest that both genes (IGF-1
and PGC-1) could be involved in ageing together .
P07.005
Allele frequency distribution for 3 microsatellite marker in
chromosome 12 in tehran Lipid and Glucose study
M. S. Daneshpour1 , M. Houshmand2 , M. Hedayati1 , S. Alfadhli3 , F. Azizi1 ;
1Obesity Research Center, Research Institute for Endocrine Sciences, Tehran,
Islamic Republic of Iran, 2Department of Medical Genetics, National Institute
for Genetic Engineering and Biotechnology, Tehran, Islamic Republic of Iran,
3Department of Medical Laboratory Sciences, Faculty of Allied Health Sciences,
Kuwait, Kuwait.
Objective To study the distribution of allele frequency of 3 microsatellite
marker (D12S96, D12S1632 and D12S329) in chromosome 12 on
a representative sample of Iranian population
Methods 534 members of 110 families were selected from Thehran
Lipid and glucose Study. The DNA samples amplified by multiplex
PCR in ABI thermal cycler. Electrophoresis of amplification product
performed on an ABI genetic analyzer. After PCR amplification and
separation by electrophoresis, raw data was compiled; analyzed and
numerical allele designations of the profiles obtained. Deviation from
Hardy-Weinberg equilibrium, observed and expected heterozygosity,
power of discrimination, and power of exclusion were calculated . Bonferroni’s
correction performed before each comparative analysis .
Results: Several new alleles (not yet reported in the NIST Short Tandem
Repeat DNA Internet Data Base [http://www .cstl .nist .gov/biotech/
strbase/]) detected in this study . We found 15 alleles for D12S96, 10
alleles for D12S1632 and finally 10 alleles for D12S329. The most hetozygote
and informative allele was D12S1632 with 0 .7270 hetrozygosity
(208-230bp) and 0.7395 PIC number. There was no significant
deviation from Hardy-Weinberg equilibrium for all the observed loci .
Conclusion: Comparing Iranian data with those obtained from
other populations, the most informative allele in this population is
D12S1632 .
P07.006
Alpha 1 antitriypsin gene mutation in patients with a suspected
alpha 1 antitrypsin protein deficiency
C. Mordillo, Y. Robles, J. Seco, L. Alvarez, A. Ortega, E. Massip, D. Gómez;
Balagué Center S.A., Hospitalet de Llobregat, Spain.
Alpha 1 antitrypsin (AAT) deficiency is the most prevalent potentially
lethal hereditary disease of Caucasians. Individuals with AAT deficiency
have an increased risk of early onset for severe pulmonary emphysema
and for liver disease . The most common variants of AAT are
classified as M, S, and the most prevalent type of clinically important
AAT deficiency, the Z genotype.
MATERIAL AND METHODS: We sequenced the coding region of the
AAT gene in 105 patients with a suspected deficiency of AAT protein.
We analyzed the sequences by comparing all exons amongst them
and also with the reported AAT sequence in the databases to identify
all known and novel allelic variants in the gene . Some patients were
also tested for plasma levels .
RESULTS: We found eight new genetic variants in the coding sequence
of the AAT gene . Two were small deletions and six were SNP´s . Some
of them changed the amino acidic sequence of the protein and were
found in more than one patient . All new genetic variants were found in
an heterozygous state .
CONCLUSION: Naturally occurring mutations have been very useful in
understanding regulation-functionality of proteins . Using the sequencing
method for genotyping, has showed to be a very useful tool for discovering
new genetic variants . The knowledge of new genetic variants
in the AAT gene, specially when they occur in the coding region of the
gene, could contribute to identify new genetic risk factors for suffering
the AAT deficiency disease.
P07.007
Phenotyping of alpha-1-antitrypsin in hospitals of three regions
of Azerbaijan
A. B. Ismayilova;
Baku State University, Baku, Azerbaijan.
Alpha-1-antitripsin (α1AT) is a low molecular protease inhibitor, synthesized
by liver cells and suppressing the activity of many serine proteoletic
enzymes . In our experiments for revealing subtypes of normal
Pi alleles: M1, M2, M3 and diagnosis of mutated alleles - PiZ, PiS we
used analytical method of isoelectrofocusing (IEF) in thin layer polyacrylamide
ampholine gels ( PAAG), pH 4-6. We have done identification
of α1AT phenotypes in quite healthy persons as well as in patients
with COPD . Capillary blood (0,2 ml) with anticoagulation agent - heparin
was collected in eppendorf tubes . Altogether there were screened
919 persons’ blood samples in 3 regions : Siyazan and Khachmas
areas are located 110 km northward and Khazakh area 450 km westnorthward
from Baku city . The frequency of mutated gene PiZ and PiS
varied in the limits of 0 .0046-0 .0114 and 0 .0037 and 0 .0066 respectively
. The lowest frequencies PiZ of the gene were revealed at population
of Khazakh, PiS gene at the population of Siyazan . Among the
patients with COPD from all centrals region hospitals there were identified
the homozygote state for PiZ mutations with phenotypic frequency
0 .83% (Khazakh) up to 1 .81% (Khachmas) at the average - 1 .16% .
Only among the patients in Siyazan there was identified compound-
i .e . double heterozygote state of PiZ and PiS genes . About the three
regions there were revealed 32 mutations of of PiZ heterozygote, homozygote
- 19 people, mutations of PiS heterozygote - 22, homozygote
one and one compound with PiZ/PiS genotype .
P07.008
Leukocyte and Plasma Alpha-Galactosidase Enzyme Activity
Levels in Healthy Young Adults: Evidence that Females Have
Higher Plasma Levels
J. Oliveira1 , S. Ferreira1 , J. Barceló1 , F. Carvalho1 , J. Månsson2 ;
1 2 Faculdade de Medicina, Universidade do Porto, Porto, Portugal, Sahlgren’s
University Hospital, Molndal, Sweden.
Background: Lysosomal α-galactosidase is the enzyme deficient
in Fabry disease, an X-linked glycosphingolipid storage disorder affecting
both genders. Although in males the leukocyte and plasma αgalactosidase
assays are used interchangeably for the diagnosis of
Fabry disease, in females the enzyme assays are less reliable and
the plasma assay apperas to have a much lower sensitivity than the
leukocyte assay .