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

Normal variation, population genetics, genetic epidemiology
P1199. Epidemiology of oculo-aruiculo-vertebral spectrum
(OAVS): a registry-based study on European population
I. Barisic 1 , V. Tokic 1 , M. Loane 2 , F. Bianchi 3 , E. Calzolari 4 , E. Garne 5 , D. Wellesley
6 , H. Dolk 2 ;
1 Childrens Univ. Hospital Zagreb, Zagreb, Croatia, 2 EUROCAT Central Registry,
University of Ulster, Newtonabbey, Co Antrim, Northern Ireland, United
Kingdom, 3 Unit of Epidemiology, CNR Institute of Clinical Physiology, Pisa,
Italy, 4 Department of Experimental and Diagnostic Medicine, Division of Medical
Genetics, University of Ferrara, Ferrara, Italy, 5 Epidemiology, University of
Southern Denmark, Odense, Denmark, 6 Wessex Clinical Genetics Service,
Princess Anne Hospital, Southampton, United Kingdom.
Oculoariculovertebral spectrum (OAVS) is a phenotypically and genetically
heterogenous disorder grouping together different conditions
thought to be caused by impaired development of the first and second
branchial arches including Goldenhar syndrome, facioauriculovertebral
syndrome, hemifacial microsomia, and otomandibular dysostosis.
We present the results of the population-based epidemiological study
on the severe end of OAV spectrum.
The data were extracted from the database of EUROCAT (European
Surveillance of Congenital Anomalies), a large European network of
birth defect registries that use the same epidemiological methodologies.
Based on data collected during the 1980-2004 period, we found
the prevalence of the severe OAVS cases to be 2.63/100 000 births
or 1/38022. The most frequently associated congenital malformations
were major ear malformations that accounted for 30% of cases
(68/224). Vertebral anomalies were reported in 30% of cases (67/224),
and cardiac defects were present in 25% of cases (57/224). Severe
central nervous system involvement was rare (17/224 - 8%). Prenatal
ultrasound examination in the period 2000-2004 detected abnormalities
in 15% (16/111) of cases. Live born infants with OAVS have a high
first week survival (98.5%). Maternal and paternal ages do not seem
to be risk factors for OAVS. Almost 35% of patients, born after the 37 th
week of gestation, weighed less than 2500 g. Among 272 patients,
consanguinity of parents was registered in 5 cases. OAVS among sibs
was found in 4 cases, while family history for OAVS was positive in additional
10 cases. No evidence of exposure to consistent teratogenic
agents including maternal diabetes was noted.
P1200. Bone mineral density variation related to islet amyloid
polypeptide (amylin) haplotypes in young and elderly women in
Southern Sweden
S. Gebre-Medhin 1 , P. Gerdhem 2 , M. Callreus 2 , K. Åkesson 2 , H. Luthman 3 ;
1 Dept Clinical Genetics, Lund University Hospital, Lund, Sweden, 2 Dept of Orthopedics,
Malmö University Hospital, Malmö, Sweden, 3 Dept of Endocrinology,
Malmö University Hospital, Malmö, Sweden.
BACKGROUND AND AIM: The candidate hormone islet amyloid polypeptide
(IAPP or amylin) is predominantly expressed by the pancreatic
beta cells and cosecreted with insulin in response to food intake. Several
studies have implied a physiological role for IAPP in bone remodeling.
For example, IAPP knockout mice exhibit increased numbers
of bone-resorbing osteoclasts and develop an osteporosis-like phenotype
in adulthood. However, the importance of IAPP in bone remodeling
in humans is not clear. In the present work we have investigated
whether different IAPP haplotypes are associated with bone mineral
density (BMD) in young women at peak bone mass and elderly women
at high risk of fracture. MATERIALS AND METHODS: 1005 young
women from the Malmö Peak-study (age 25±0.1 yrs, BMI 23.0±3.7
kg/cm2) and 1044 elderly women (Malmö OPRA-study; age 75±0.1
yrs, BMI 26.2±4.2 kg/cm2) were recruited. The primary phenotype was
BMD assessed by DXA. Body composition data, calcaneus ultrasound
estimates and fracture data (OPRA-study) were also available. Short
nucleotide polymorphisms (SNPs) in the vicinity of the IAPP gene
were retrieved from the International HapMap Genotype Database and
genotyped by PCR using the ABI SNP genotyping assay. RESULTS
AND DISCUSSION: Obtained data and an update of this study will be
presented.
P1201. Model free Lods for linkage analysis of large complex
pedigrees
I. V. Zorkoltseva, T. I. Axenovich;
Institute of Cytology and Genetics, Novosibirsk, Russian Federation.
Parametric linkage analysis is a powerful tool for mapping genes for
complex traits. When mode of inheritance is unknown, it was suggested
01
to use model free Lod score for linkage analysis. The statistical properties
of different parametric linkage tests have been compared for small
pedigrees, but remain unknown for large extended pedigrees.
We compared model based and model free Lod score statistics for
multipoint linkage analysis in a large complex human pedigree with
multiple loops. We simulated quantitative traits with dominant, additive
or recessive major gene effect and genotypes for a set of five-allelic
markers. Three linkage statistics were compared: Lod, using true
underlying QTL model parameters; PLod, based on the estimations
of model parameters coming from complex segregation analysis and
MFLod, estimating model parameters and the QTL position simultaneously.
We used approximate likelihood calculation based on the loop
breaking (Stricker et al., 1995).
For all analyzed models average values of the test statistics and the
portion of experiments in which the test was >3, were highest for
MFLod and lowest for the PLod. However, it is known that the distribution
of multipoint Lod score under H 0 depends on frequencies of
alleles, mode of inheritance, and so on. We analyzed type I errors for
used linkage statistics and demonstrated that they are similar for Lod
and PLod, but higher for MFLod. Nevertheless linkage power calculated
on the base of empirical threshold level was higher for MFLod
than for Plod or Lod.
P1202. Combinatorial genetic analysis of physical performance
in athletes
I. I. Ahmetov, I. V. Astratenkova, A. M. Druzhevskaya, V. A. Rogozkin;
St Petersburg Research Institute of Physical Culture, St Petersburg, Russian
Federation.
It has been shown physiologically that for rowing at least 70% of the
energy requirement comes from aerobic metabolism; the remainder
comes from anaerobic sources. Accumulating evidence suggests that
polymorphisms of ACE, ACTN3 and PPARA genes are strongly influence
human physical performance. ACE I and PPARA G alleles are
supposed to be favorable for endurance-oriented athletes, whilst ACE
D, PPARA C and ACTN3 R alleles are thought to enhance power performance.
The purpose of this study was to determine genotype and
allele frequencies of ACE I/D, ACTN3 R577X and PPARA G/C polymorphisms
in rowers and to detect genotype combinations that are
prevalent in elite, sub-elite and non-elite rowers compared to controls.
173 male and female Russian elite, sub-elite and non-elite rowers and
842 controls were recruited for the study. Genotyping was carried out
by RLFP. We found that frequencies of ACE D and PPARA C alleles
were the lowest in elite level rowers compared to other rowers and controls.
ACTN3 X allele frequency tended to decrease with athletes’ improvement
of elite status. When all endurance-associated alleles were
combined, we determined common endurance alleles frequencies in
different groups. The highest value of endurance alleles frequency was
observed in male elite (72.2%) and female sub-elite rowers (70.5%),
compared to male (66.0%) and female controls (66.1%), respectively.
The prevalent combination of genotypes in all groups was ID-RX-GG.
The frequency of this combination was highest in elite rowers (28.6%);
the lowest was found in controls (17.3%).
P1203. POLG disease mutations in Europe, Australia, New
Zealand, and the USA explained by single ancient European
founders
A. H. Hakonen 1 , G. Davidzon 2 , R. Salemi 3 , L. A. Bindoff 4 , G. Van Goethem 5,6 ,
S. DiMauro 2 , D. R. Thorburn 3 , A. Suomalainen 1,7 ;
1 Research Program of Molecular Neurology, Biomedicum-Helsinki, University
of Helsinki, Helsinki, Finland, 2 Department of Neurology, Columbia University
Medical Center, New York, NY, United States, 3 Murdoch Children’s Research
Institute, Royal Children’s Hospital and Department of Paediatrics, University of
Melbourne, Melbourne, Australia, 4 Department of Neurology, Institute of Clinical
Medicine, University of Bergen & Haukeland University Hospital, Bergen, Norway,
5 Division of Neurology and the Neuromuscular Reference Center, University
Hospital Antwerp, Antwerp, Belgium, 6 Department of Molecular Genetics,
Neurogenetics group, VIB and University of Antwerp, Antwerp, Belgium, 7 Department
of Neurology, Helsinki University Central Hospital, Helsinki, Finland.
Mutations in the catalytic subunit of the mitochondrial DNA polymerase
gamma (POLG) have been found to be an important cause of neurological
disease. We and collaborators have identified the POLG
W748S mutation as the underlying cause of mitochondrial recessive
ataxia syndrome (MIRAS) and found it to be among the most common