2008 Barcelona - European Society of Human Genetics

Normal variation, population genetics, genetic epidemiology
that these loci can be useful for human identification in forensic cases in
Iran . We must pay attention that typing success in loci ranges from 100
± 150 base pairs is better especially with degraded DNA samples .
P07.075
Identification of a geographic area characterized by
“reproductive longevity” in the sardinia island
P. Astolfi 1 , G. Caselli 2 , O. Fiorani 3 , R. M. Lipsi 2 , A. Lisa 3 , S. Tentoni 4 ;
1 Dept. Genetics and Microbiology, University, Pavia, Italy, 2 Dept. Demographic
Sciences, University, Rome, Italy, 3 IGM, CNR, Pavia, Italy, 4 IMATI, CNR, Pavia,
Italy.
Sardinian population differs from the Italian mainland and other European
populations in demographic and biological traits, resulting from
the socio-economic structure and the geographical and historical isolation
. Its reproductive behaviour is characterized by the historical and
still present tendency to late maternity . We hypothesize that areas of
“reproductive longevity” exist throughout the island, where a higher
incidence of elderly mothers combines with a lower risk of perinatal
death . Data regard all 1980-96 births (n=299,793), occurred in 363
Sardinian municipalities . Through a smoothed isopleth mapping procedure,
we explored the spatial distributions of a late maternity indicator
(proportion of 35+year-old mothers), and a perinatal mortality
indicator (proportion of deaths within the 1 st week of life) associated
with late maternity . We drew critical isopleths to highlight “excess” areas,
where the late maternity indicator exceeds the average Sardinian
value and approaches its upper limit . With respect to the “non excess”
area (23% of 35+year-old mothers), in the “highest excess” area (27%
of 35+year-old mothers) the Odds Ratio of perinatal death was lower
(1 .38 vs 1 .78), and the proportion of consanguineous marriages and
the inbreeding coefficient were respectively from 3 to 2.4 fold higher.
In conclusion we suggest that such area, located in the central part
of the island and qualified for “reproductive longevity”, can be target
of further investigations on eventual protective mechanisms against
adverse perinatal outcomes in late maternity, and of studies on the
possible association between reproductive longevity and achievement
of an extended life span .
P07.076
High frequency of LCHAD deficiency carriers in the northern
Poland
D. Piekutowska-Abramczuk 1 , R. K. J. Olsen 2 , J. Wierzba 3 , E. Popowska 1 , D.
Jurkiewicz 1 , K. Czornak 1 , P. Kowalski 1 , M. Borucka-Mankiewicz 1 , E. Ciara 1 , J.
Sykut-Cegielska 1 , W. Gradowska 1 , M. Krajewska-Walasek 1 , N. Gregersen 2 , E.
Pronicka 1 ;
1 Children’s Memorial Health Institute, Warsaw, Poland, 2 University Hospital,
Skejby Sygehus, Aarhus, Denmark, 3 Medical Academy, Gdansk, Poland.
Long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency is
an autosomal recessive disorder of mitochondrial fatty acid oxidation .
It is the most common defect of the mitochondrial trifunctional protein
(MTP) complex which catalyzes the last three steps of the β-oxidation
spiral of long-chain fatty acids . The gene HADHA for the α-subunit of
MTP carrying LCHAD activity is located on chromosome 2p23 . 60-86%
of reported patients with isolated LCHAD deficiency have a prevalent
c .1528G>C mutation .
Our earlier screening of urinary GC-MS organic acid profile and MS-
MS blood acylcarnitines profile in Polish children revealed the presence
of 40 patients (37 families) with LCHAD deficiency. The common
c .1528G>C substitution was observed on 89% of mutated alleles . A
tendency for clustering the LCHAD deficient patients in northern part of
Poland, especially in Pomeranian voivodeship, was found .
The aim of our study was to identify carrier frequency of the common
mutation in various districts of northern Poland to verify the probability
of correlation between high number of Pomeranian patients and expected
high carrier frequency of the c .1528G>C mutation carriers .
Up to now, 1096 blood samples collected on anonymous Guthrie
cards, have been screened . Seven heterozygotes for c .1528G>C mutation
(including 4 carriers from the Pomeranian region) were detected .
No samples homozygous for the c.1528C allele were identified. The
preliminary study suggests that LCHAD deficiency carriers are more
prevalent in the areas around the Baltic sea than in other parts of the
world .
The study was partly supported by the Polish Ministry of Science Project
0678/B/P01/2007/33
P07.077
Association analysis of G- A and A G polymorphisms in
the human leptin gene with obesity
Z. Tomas 1 , N. Smolej Narancic 1 , M. Barbalic 1 , M. Zajc 1 , T. Skaric-Juric 1 , P.
Rudan 1 , I. Rudan 2 , H. Campbell 3 , A. F. Wright 4 ;
1 Institute for Anthropological Research, Zagreb, Croatia, 2 “Andrija Stampar”
School of Public Health, School of Medicine, University of Zagreb, Zagreb,
Croatia, 3 Department of Public Health Sciences, University of Edinburgh, Medical
School, Edinburgh, United Kingdom, 4 MRC Human Genetics Unit, Western
General Hospital, Edinburgh, United Kingdom.
Leptin is a protein hormone which plays an important role in the regulation
of body adiposity, lipid metabolism and reproductive function .
It is primarily secreted by the adipocytes and its concentration in the
blood is proportional to the amount of body fat . Many leptin gene polymorphisms
have been found, but their association with obesity is still
controversial . We tested the polymorphisms G-2548A in promoter region
and A19G in intron 1 of leptin gene for association with leptin
concentration in the blood and obesity . A population-based association
study was conducted in the population isolate of the Eastern Adriatic
island of Vis, Croatia . Three hundred and twenty randomly selected
subjects from the Vis population were genotyped . Obesity was defined
as BMI≥30 kg/m 2 . The results revealed significant association
of G-2548A variant and leptin concentration in a codominant pattern
(p=0 .026) . The ancestral G allele which displays as a minor allele in
the Vis population (frequency of 0 .44) was associated with higher
leptin levels. The leptin concentration was significantly higher in the
obese (60 .1 ng/ml, N=244), than in the non-obese group (20 .7 ng/ml,
N=76) and it was more than three times higher in women (44 .0 ng/ml)
compared to men . However, no association of G-2548A and A19G
polymorphisms with obesity was found (with leptin concentration, sex
and age as covariates) . The results indicate that the studied polymorphisms
are not relevant markers for common obesity in this isolated
population, but were found to influence the leptin concentration which
is an obesity-related phenotype .
P07.078
High level of genetic differentiation in siberian populations
demonstrated by ZFX haplotypes
I. Khitrinskaya, V. Kharkov, V. Stepanov;
Institute for Medical Genetics, Tomsk, Russian Federation.
X-Chromosome is considered as a convenient instrument used to
study genetic history of populations . Firstly, since men have only one
copy of X-chromosome it is easy to determine haplogroups . Linkage
disequilibrium is also greater on the X-chromosome, because only
two-thirds of this chromosome manages to recombine in each generation
. The size of regions with a single genetic history is expected to be
larger than in autosomes, once more making it ideal for human population
genetic studies . In our study we have analyzed 5 SNP (rs2238925,
rs2238926, rs2238928, rs2704843 and rs2704849) in ZFX gene located
in Xp21 .3 locus on the X-chromosome . Human populations belonged
to 11 ethnic groups residing in Siberia and Middle Asia (Russians,
Altaians, Buryats, Kets, Khants, Kirghizes, Komis, Tajiks, Tuvinians,
Uzbeks and Yakuts) have been studied . Altogether 1073 male
individuals were analyzed . Genetic differentiation of the ethnic groups
under study was estimated using AMOVA analysis . General level of
genetic differentiation for the investigated populations at the level of
ethnic groups amounted to 3 .6% . The North Siberian population (Kets,
Yakuts and Khants) is most highly differentiated (F ST = 11 .2%), for the
other groups (Central Asia, South Siberia and East Europe) a degree
of genetic differentiation does not exceed 1% . Structural analysis of
the selected SNP revealed 19 haplotypes . Median networks demonstrate
the occurrence of two haplotype clusters, which may be conditionally
determined as “Mongoloid” and “Caucasoid” . Linkage analysis
revealed a high LD level for 9 groups, excluding Ket and Uzbek populations
.