2008 Barcelona - European Society of Human Genetics
2008 Barcelona - European Society of Human Genetics 2008 Barcelona - European Society of Human Genetics
Genetic analysis, linkage, and association was found according the allele and genotype frequencies of the investigated polymorphisms . AMPD1 heterozygous male athletes in the “Anaerobic” group showed greater Mean Power Output (Watts) in comparison to CC homozygous athletes (9,11 vs. 7,34 Watts). Significant correlation was observed also with the buffering capacity (HCO3 and BE) . No Individuals homozygous for the T-allele of AMPD1 were found . The ACTN3 genotype correlated with parameters relevant to exercise capacity such as oxygen uptake, saturation and Lean Body Mass in the male sub-groups of anaerobic sports and endurance sports, but not in the female sub-groups . P06.005 case-control study of six genes asymmetrically expressed in the two cerebral hemispheres: evidence of association of BAIAP and NEUROD with adulthood attention-deficit hyperactivity disorder M. Ribases 1,2 , R. Bosch 1 , A. Hervás 3 , J. Ramos-Quiroga 1,4 , A. Bielsa 1 , X. Gastaminza 1 , M. Fernández-Anguiano 3 , M. Nogueira 1 , N. Gómez-Barros 1 , X. Estivill 5,6 , M. Casas 1,4 , M. Bayés 5,6 , B. Cormand 7,8 ; 1 Department of Psychiatry, Hospital Universitari Vall d’Hebron, Barcelona, Spain, 2 Research Group in Childhood Neurology and Psychiatric Genetics, Hospital Universitari Vall d‘Hebron, Barcelona, Spain, 3 Child and Adolescent Mental Health Unit, Hospital Mútua de Terrassa, Barcelona, Spain, 4 Department of Psychiatry and Legal Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain, 5 Genes and Disease Program, Center for Genomic Regulation (CRG), UPF, Barcelona, Spain, 6 CIBER Epidemiología y Salud Pública, Instituto de Salud Carlos III (CRG), Barcelona, Spain, 7 Departament de Genètica, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain, 8 CIBER Enfermedades Raras, Instituto de Salud Carlos III, Barcelona, Spain. Attention-deficit hyperactivity disorder (ADHD) is a common childhood-onset neuropsychiatric disorder that persists throughout lifespan in at least 30% of ADHD children . Different lines of evidence suggest that abnormal right-left brain asymmetries in ADHD patients may be involved in a variety of ADHD-related cognitive processes, including sustained attention, working memory, response inhibition and planning . Although the exact mechanisms underlying cerebral lateralization are unknown, left-right cortical asymmetry in humans has been associated with transcriptional asymmetry at early embryonic stages and a number of genes differentially expressed between hemispheres have been identified. Among these, we selected six functional candidate genes showing at least 1 .9-fold differential expression between hemispheres (BAIAP2, DAPPER1, LMO4, NEUROD6, ATP2B3, ID2) and performed a case-control analysis in 531 ADHD patients (320 children and 211 adults) and 531 sex-matched unrelated controls . The single- and multiple-marker analysis provided preliminary evidence for the contribution of BAIAP2 (P=8 .5e-06; OR = 2 .69 (1 .74-4 .17)) and NEUROD6 (P = 0 .0053, OR = 1 .76 (1 .18-2 .61)) to adulthood ADHD . Additionally, association between both genes and performance deficits in the Conners Continuous Performance Test (CPT-II) was also identified. Our results support the participation of BAIAP2 and NEUROD6 in the continuity of ADHD across lifespan and suggest that genetic factors potentially influencing abnormal cerebral lateralization may be involved in the predisposition to this neurodevelopmental disorder . P06.006 the genetic causes of sex differences in neurodevelopmental disorders E. Stergiakouli, H. Williams, K. Langley, A. Thapar, M. J. Owen; Department of Psychological Medicine, Cardiff University, Cardiff, United Kingdom. ADHD and schizophrenia are heritable, neurodevelopmental disorders that are more prevalent in males . Both disorders also show sex differences in age of onset and severity . The Y chromosome is potentially an important influence on male susceptibility to neuropsychiatric disorders . Animal models have associated the Y chromosome with aggression and decreased levels of serotonin and dopamine in the brain. However, due to difficulties arising from the lack of recombination and widely accepted nomenclature, the Y chromosome has been largely excluded from genetic and genomic studies of neuropsychiatric disorders . . In order to overcome this lack of knowledge we chose to study the Y chromosome in a sample of 210 cases with ADHD, 310 cases with schizophrenia and 700 U .K . controls . In total, 40 Y chromosome markers were selected to represent the main Y chromosome haplogroups that are present in the U .K . according to data from the Y chromosome Consortium data and personal communication with Y chromosome researchers . Statistical analysis of Y chromosome haplogroup analysis revealed no significantly increased representation of any haplogroup in cases with ADHD or schizophrenia compared to controls . However, this is one of the few studies to have genotyped Y chromosome markers in such a large number of U .K . individuals and therefore our results provide an insight into the population structure of U .K . Y chromosome haplogroups . P06.007 The influence of adiponectin G276T gene polymorphism on changes in adiponectin levels or its oligomer composition by exercise training D. Ando 1 , Y. Hosaka 2 , K. Suzuki 1 , Z. Yamagata 1 ; 1 School of Medicine, Chuo, Japan, 2 Hosaka Clinic, Fujiyoshida, Japan. Purpose: Exercise training improves glucose and lipid metabolism mediated by altered adiponectin oligomer composition . The purpose is to determine the effects of exercise training on total and high molecular weight (HMW) adiponectin and adiponectin oligomeric distribution and influence of adiponectin G276T gene polymorphism on changes in adiponectin levels or its oligomer composition by exercise training . Subjects and Methods: A randomized parallel-design study (n = 53; 36 women and 17 men; aged 32-65 years) at a fitness club from April 2006 to July 2007 was conducted . Participants were randomly assigned to the exercise (n = 26) or control (n = 27) group and received exercise training for 70 min 2 times per week for 12 weeks and exercise advice at the baseline, respectively . Main outcome are muscle strength; body weight; body mass index; blood pressure; glucose and lipid parameter; circulating levels of total adiponectin and HMW adiponectin; and percentage of HMW adiponectin . Results: After 12 weeks, there were no differences between the groups for the total adiponectin levels, HMW adiponectin levels, or percentage of HMW adiponectin. No significant difference in the change in the total and HMW adiponectin levels and the percentage of HMW adiponectin between the subjects with the G276G genotype and 276T allele carriers were found in either the exercise or control group . Conclusion: In the absence of weight loss, Exercise training, does not change HMW adiponectin levels or the adiponectin oligomer composition . Adiponectin G276T gene polymorphism may not modify the adiponectin change response to exercise training . P06.008 Genetic analysis of adult stature in Dutch isolated population I. V. Zorkoltseva 1 , T. I. Axenovich 1 , C. M. van Duijn 2 ; 1 Institute of Cytology and Genetics, Novosibirsk, Russian Federation, 2 Department of Epidemiology & Biostatistics, Erasmus MC, Rotterdam, Netherlands. We analysed a large complex pedigree from a Dutch genetically isolated population . About 2600 of 19700 pedigree members were phenotyped and genotyped for autosomal 5208 SNPs (Illumina 6K linkage panel) . Complex segregation analysis of adult height was performed under mixed model including effects of biallelic major gene, polygene, age and sex . We used likelihood approximation based on breaking pedigree loops. The results confirmed large contribution of genes in the trait variance (h 2 = 0.85 ) and significance of major gene effect in accordance with Elston-Stewart test . Three genotypic means were estimated as 183 .5, 178 .3 and 174 .6 cm in males at 40 years with average difference of male and female genotypic means about 13 cm . The putative major gene explained 18% of trait variance . A genome-wide scan was performed by variance-components method using Merlin program . Prior to analysis, the pedigree was split into smaller non-overlapping fragments, with maximum bit-size of 18 . No loci demonstrated significant linkage, however for 6 loci linkage was suggestive: SNP Chr Position(cM) LodScore rs1993104 19 56 .9 2 .71 rs1873191 18 44 .7 2 .60 rs1019845 2 195 .8 2 .27 rs958883 5 123 .3 2 .15 rs936347 16 17 .2 2 .11 rs216223 17 2 .1 2 .11 Of these six loci, five were identified in previous linkage analyses, while locus at chromosome 16 (rs936347) was new.
Molecular and biochemical basis of disease P06.009 A candidate phenotypic modifier gene in fibrinogen deficient mice: beta-1,4-N-acetyl-galactosaminyl transferase 1 (galgt1) R. J. Fish 1 , D. Vu 1 , A. Fort 1 , S. Deutsch 1 , J. Degen 2 , M. Neerman-Arbez 1 ; 1 Geneva University Faculty of Medicine, Geneva, Switzerland, 2 Cincinnati Children’s Hospital Research Foundation and University of Cincinnati College of Medicine, Cincinnati, OH, United States. In humans the absence of circulating fibrinogen leads to a bleeding disorder with variable severity, afibrinogenemia. Fibrinogen alpha chain knock-out mice (FGA-/-) are effectively afibrinogenemic and show a strain-specific bleeding phenotype in neonates. This variability implies that modifier genes exist in FGA-/- mice and in humans with afibrinogenemia . About 70% of C57BL/6 FGA-/- mice die in the neonatal period whereas survivors have normal longevity . Fewer (~20%) FVB/N FGA-/- mice die as neonates but show high mortality at P30 to P60 . To identify candidate FGA-/- phenotypic modifier genes, we used microarray analysis on liver RNA from both mouse strains . Of the genes identified with variable expression between strains, one encodes a Beta-1,4- N-acetyl-galactosaminyl transferase (galgt1) . A galgt1 paralog, galgt2, was identified as a modifier gene in a mouse model of another human bleeding disorder, von Willebrand’s disease(1) . By RT-PCR, we found that galgt1 expression increases in the liver of C57BL/6 mice from P0 to P30 . In contrast, galgt1 expression is low in FVB/N mice at birth and declines with age. Using strain-specific polymorphisms and sequencing of RT-PCR products, we determined the expression of C57BL/6 and FVB/N galgt1 alleles in livers from F1 hybrid mice . Both alleles were expressed at P0, but only the C57BL/6 allele was detected at P30 . Using pyrosequencing, the FVB/N allele expression was 22 .8% at P0 and undetectable at P30 . We are investigating the genetic basis for this differential allelic expression and whether it can explain strainspecific phenotypic variation in FGA-/- mice. (1)Mohlke et al, (1999) Cell, 96, p111-120 . P06.010 Identification of susceptibility genes for Multiple sclerosis: a study of the genomic region 2q13-14 in an italian population I. Borzani1 , M. Tola1 , L. Caniati2 , G. De Santis1 , A. R. Collins3 , C. Scapoli1 ; 1 2 3 University of Ferrara, Ferrara, Italy, St. Anna Hospital, Ferrara, Italy, University of Southampton, Southampton, United Kingdom. Understanding the genetic basis of multiple sclerosis (MS) remains a major challenge, despite decades of intensive researches . Whole genome linkage studies were carried out in different populations and from these analyses the prediction of at least 38 potential non-MHC susceptibility regions emerged (Abdeen et al ., 2006) . Among these, chromosomal portions of specific interest to some populations came out: the region 2q14 in the Irish and English population (Heggarty et al ., 2003; Mann et al ., 2002), the region 2q36 in the Sardinians (Coraddu et al, 2003) and the region 2p21-22 in Continental Italian population (Liguori et al ., 2003) . The main objective of this study was to investigate the role of 2q13-14 region in the pathogenesis of MS . The investigation was conducted on 120 patients, with clinically defined MS, and on 249 healthy subjects collected from the North-Italian population . Using CHROMSCAN (Maniatis et al, 2002, 2005), a map in LD-units, under the Malécot model for multiple markers, was constructed . The block-step structure of the 2q13-14 region was based on 70 SNPs (validated in the Caucasian population) selected from the HapMap database, with rare variant frequencies higher than 10% and evenly covering a region of 1 .2 Mb within the segment 2q13-14 . We tested the association with the disease through both allelic association and by association mapping with the Malécot Model (Morton et al . 2007) . The present results support a possible association between this candidate region and MS in the North-Italian population . P06.011 Association between the N-acetyltransferase 2 (NAt2) gene polymorphisms and allergic rhinitis in Volga-Ural region of Russia A. Khuzina 1 , A. Karunas 1 , A. Biktasheva 2 , A. Yuldasheva 3 , E. Etkina 2 , E. Khusnutdinova 1 ; 1 Institute of Biochemistry and Genetics, Ufa Scientific Center, Russian Academy of Sciences, Ufa, Russian Federation, 2 Bashkir Medical State University, Ufa, Russian Federation, 3 Pediatric polyclinic N1, Ufa, Russian Federation. Allergic rhinitis (AR) is the result of an immunologically mediated hypersensitivity reaction of the nasal mucosa, initiated by exposure to specific allergens. The prevalence of AR in various countries ranges from 10-25% . It has been suggested in various studies that genetic defects in acetylation may be involved in the pathogenesis of allergic diseases and atopy . The aim of this study was to examined the allele and genotype frequencies of three polymorphisms (481C>T, 590G>A, 857G>A) of the gene and analysed their combinations . The patient group consisted of 264 individuals with AR with different ethnic origins (Russians, Tatars, Bashkirs), the control group included 185 unrelated non-allergic individuals . The NAT2 alleles (*4, *5, *6, and *7) were determined by polymerase chain reaction-restriction fragment length polymorphism methods with DNA extracted from peripheral blood leucocytes by standard phenol/chloroform method . The analysis has revealed that Tatars have significant higher frequency of *4 allele (wild type) of the NAT2 gene in control group than in patients (P=0,0007; OR=0,34; 95%CI=0,18-0,64) . At comparison of group of patients with high total IgE level and the control group we have also determined increased frequency of *4 allele of the NAT2 gene in healthy donors (P=0,026; OR=0,53; 95%CI=0,3-0,93) . Moreover, an association of *5*6 genotype of the NAT2 gene with AR at patients with high total IgE level has been found (P=0,012; OR=2,4; 95%CI=1,19-4,82) . Thus, we have determined statistically significant association between NAT2 gene polymorphisms and allergic rhinitis in Volga-Ural region of Russia . P06.012 inherited alopecia and ectodermal dysplasia in pakistani kindereds I. Ahmad, M. Tariq, A. Ali, M. Bakhtiar, A. Azhar, S. M. Baig; National Institute for Biotechnology and Genetic Engineering (NIBGE), Faisalabad, Pakistan. Inherited Alopecia (AP) is a rare autosomal recessive disease clinically characterized by total or partial hair loss soon after their birth and the development of papular lesions of keratin-filled cysts over extensive area of body . The inherited hypohidrotic and anhydrotic ectodermal dysplasia (ED) is characterized by the absence or hypoplasia of hair, teeth and eccrine sweat gland . Ecotodermal dysplasias are highly heterogeneous with more than 200 distinct clinical forms reported so far . The X-linked hypohidrotic ectodermal dysplasia (XLED) is the most common form of ED . In this study, twelve consanguineous families with alopecia and seven with ectodermal dysplasia were ascertained from Southern Punjab and Northern areas of Pakistan having multiple affected members . Pedigrees were analyzed to determine the pattern of inheritance; in four families with AP the disease was inherited in the autosomal recessive pattern . Short Tandem Repeat Markers (STR) were used in the exclusion mapping for the ten most common loci reported . According to results, one family with AP was linked to the type 1 keratin genes (17q21 .2locus) while other families are still undergoing exclusion analysis . In four families with ED exclusion to all known loci has been observed whereas one family is showing linkage to the type II keratin (KRT) genes (12q13 .13 locus) . Exclusion analysis is in process in two pedigrees with ED . The families excluded to all known loci will be subjected to genome wide scan by SNP (Single Nucleotide Polymorphism) analysis using Affymetrix 250K array system to find the homozygous regions to find out the locus having the disease gene. Statistical analysis such as LOD (log of odds) will be used to validate the data obtained . P06.013 Alpha-synuclein in familial Parkinson‘s disease and Lewy Body Dementia V. Greco 1 , E. De Marco 1 , F. Rocca 1 , P. Tarantino 1 , F. Annesi 1 , D. Civitelli 1 , G. Provenzano 1 , V. Scornaienchi 1 , I. Cirò Candiano 1 , S. Carrideo 1 , G. Squillace 1 , G. Nicoletti 1,2 , G. Annesi 1 ; 1 Institute of Neurological Sciences, National Research Council, Mangone (Cosenza), Italy, 2 Institute of Neurology, University Magna Graecia, Catanzaro, Italy. Alpha-synuclein has been implicated in the pathology of certain neurodegenerative diseases, including Parkinson’s disease (PD) and de- 0
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Genetic analysis, linkage, and association<br />
was found according the allele and genotype frequencies <strong>of</strong> the investigated<br />
polymorphisms . AMPD1 heterozygous male athletes in the<br />
“Anaerobic” group showed greater Mean Power Output (Watts) in comparison<br />
to CC homozygous athletes (9,11 vs. 7,34 Watts). Significant<br />
correlation was observed also with the buffering capacity (HCO3 and<br />
BE) . No Individuals homozygous for the T-allele <strong>of</strong> AMPD1 were found .<br />
The ACTN3 genotype correlated with parameters relevant to exercise<br />
capacity such as oxygen uptake, saturation and Lean Body Mass in<br />
the male sub-groups <strong>of</strong> anaerobic sports and endurance sports, but<br />
not in the female sub-groups .<br />
P06.005<br />
case-control study <strong>of</strong> six genes asymmetrically expressed in the<br />
two cerebral hemispheres: evidence <strong>of</strong> association <strong>of</strong> BAIAP<br />
and NEUROD with adulthood attention-deficit hyperactivity<br />
disorder<br />
M. Ribases 1,2 , R. Bosch 1 , A. Hervás 3 , J. Ramos-Quiroga 1,4 , A. Bielsa 1 , X.<br />
Gastaminza 1 , M. Fernández-Anguiano 3 , M. Nogueira 1 , N. Gómez-Barros 1 , X.<br />
Estivill 5,6 , M. Casas 1,4 , M. Bayés 5,6 , B. Cormand 7,8 ;<br />
1 Department <strong>of</strong> Psychiatry, Hospital Universitari Vall d’Hebron, <strong>Barcelona</strong>,<br />
Spain, 2 Research Group in Childhood Neurology and Psychiatric <strong>Genetics</strong>,<br />
Hospital Universitari Vall d‘Hebron, <strong>Barcelona</strong>, Spain, 3 Child and Adolescent<br />
Mental Health Unit, Hospital Mútua de Terrassa, <strong>Barcelona</strong>, Spain, 4 Department<br />
<strong>of</strong> Psychiatry and Legal Medicine, Universitat Autònoma de <strong>Barcelona</strong>,<br />
<strong>Barcelona</strong>, Spain, 5 Genes and Disease Program, Center for Genomic Regulation<br />
(CRG), UPF, <strong>Barcelona</strong>, Spain, 6 CIBER Epidemiología y Salud Pública,<br />
Instituto de Salud Carlos III (CRG), <strong>Barcelona</strong>, Spain, 7 Departament de Genètica,<br />
Facultat de Biologia, Universitat de <strong>Barcelona</strong>, <strong>Barcelona</strong>, Spain, 8 CIBER<br />
Enfermedades Raras, Instituto de Salud Carlos III, <strong>Barcelona</strong>, Spain.<br />
Attention-deficit hyperactivity disorder (ADHD) is a common childhood-onset<br />
neuropsychiatric disorder that persists throughout lifespan<br />
in at least 30% <strong>of</strong> ADHD children . Different lines <strong>of</strong> evidence suggest<br />
that abnormal right-left brain asymmetries in ADHD patients may be<br />
involved in a variety <strong>of</strong> ADHD-related cognitive processes, including<br />
sustained attention, working memory, response inhibition and planning<br />
. Although the exact mechanisms underlying cerebral lateralization<br />
are unknown, left-right cortical asymmetry in humans has been<br />
associated with transcriptional asymmetry at early embryonic stages<br />
and a number <strong>of</strong> genes differentially expressed between hemispheres<br />
have been identified. Among these, we selected six functional candidate<br />
genes showing at least 1 .9-fold differential expression between<br />
hemispheres (BAIAP2, DAPPER1, LMO4, NEUROD6, ATP2B3, ID2)<br />
and performed a case-control analysis in 531 ADHD patients (320 children<br />
and 211 adults) and 531 sex-matched unrelated controls . The<br />
single- and multiple-marker analysis provided preliminary evidence for<br />
the contribution <strong>of</strong> BAIAP2 (P=8 .5e-06; OR = 2 .69 (1 .74-4 .17)) and<br />
NEUROD6 (P = 0 .0053, OR = 1 .76 (1 .18-2 .61)) to adulthood ADHD .<br />
Additionally, association between both genes and performance deficits<br />
in the Conners Continuous Performance Test (CPT-II) was also identified.<br />
Our results support the participation <strong>of</strong> BAIAP2 and NEUROD6<br />
in the continuity <strong>of</strong> ADHD across lifespan and suggest that genetic<br />
factors potentially influencing abnormal cerebral lateralization may be<br />
involved in the predisposition to this neurodevelopmental disorder .<br />
P06.006<br />
the genetic causes <strong>of</strong> sex differences in neurodevelopmental<br />
disorders<br />
E. Stergiakouli, H. Williams, K. Langley, A. Thapar, M. J. Owen;<br />
Department <strong>of</strong> Psychological Medicine, Cardiff University, Cardiff, United Kingdom.<br />
ADHD and schizophrenia are heritable, neurodevelopmental disorders<br />
that are more prevalent in males . Both disorders also show sex differences<br />
in age <strong>of</strong> onset and severity . The Y chromosome is potentially<br />
an important influence on male susceptibility to neuropsychiatric<br />
disorders . Animal models have associated the Y chromosome with<br />
aggression and decreased levels <strong>of</strong> serotonin and dopamine in the<br />
brain. However, due to difficulties arising from the lack <strong>of</strong> recombination<br />
and widely accepted nomenclature, the Y chromosome has been<br />
largely excluded from genetic and genomic studies <strong>of</strong> neuropsychiatric<br />
disorders . . In order to overcome this lack <strong>of</strong> knowledge we chose to<br />
study the Y chromosome in a sample <strong>of</strong> 210 cases with ADHD, 310<br />
cases with schizophrenia and 700 U .K . controls . In total, 40 Y chromosome<br />
markers were selected to represent the main Y chromosome<br />
haplogroups that are present in the U .K . according to data from the<br />
Y chromosome Consortium data and personal communication with Y<br />
chromosome researchers . Statistical analysis <strong>of</strong> Y chromosome haplogroup<br />
analysis revealed no significantly increased representation <strong>of</strong><br />
any haplogroup in cases with ADHD or schizophrenia compared to<br />
controls . However, this is one <strong>of</strong> the few studies to have genotyped Y<br />
chromosome markers in such a large number <strong>of</strong> U .K . individuals and<br />
therefore our results provide an insight into the population structure <strong>of</strong><br />
U .K . Y chromosome haplogroups .<br />
P06.007<br />
The influence <strong>of</strong> adiponectin G276T gene polymorphism on<br />
changes in adiponectin levels or its oligomer composition by<br />
exercise training<br />
D. Ando 1 , Y. Hosaka 2 , K. Suzuki 1 , Z. Yamagata 1 ;<br />
1 School <strong>of</strong> Medicine, Chuo, Japan, 2 Hosaka Clinic, Fujiyoshida, Japan.<br />
Purpose: Exercise training improves glucose and lipid metabolism mediated<br />
by altered adiponectin oligomer composition . The purpose is to<br />
determine the effects <strong>of</strong> exercise training on total and high molecular<br />
weight (HMW) adiponectin and adiponectin oligomeric distribution and<br />
influence <strong>of</strong> adiponectin G276T gene polymorphism on changes in adiponectin<br />
levels or its oligomer composition by exercise training .<br />
Subjects and Methods: A randomized parallel-design study (n = 53; 36<br />
women and 17 men; aged 32-65 years) at a fitness club from April 2006<br />
to July 2007 was conducted . Participants were randomly assigned to<br />
the exercise (n = 26) or control (n = 27) group and received exercise<br />
training for 70 min 2 times per week for 12 weeks and exercise advice<br />
at the baseline, respectively . Main outcome are muscle strength; body<br />
weight; body mass index; blood pressure; glucose and lipid parameter;<br />
circulating levels <strong>of</strong> total adiponectin and HMW adiponectin; and percentage<br />
<strong>of</strong> HMW adiponectin .<br />
Results: After 12 weeks, there were no differences between the groups<br />
for the total adiponectin levels, HMW adiponectin levels, or percentage<br />
<strong>of</strong> HMW adiponectin. No significant difference in the change in the total<br />
and HMW adiponectin levels and the percentage <strong>of</strong> HMW adiponectin<br />
between the subjects with the G276G genotype and 276T allele carriers<br />
were found in either the exercise or control group .<br />
Conclusion: In the absence <strong>of</strong> weight loss, Exercise training, does not<br />
change HMW adiponectin levels or the adiponectin oligomer composition<br />
. Adiponectin G276T gene polymorphism may not modify the adiponectin<br />
change response to exercise training .<br />
P06.008<br />
Genetic analysis <strong>of</strong> adult stature in Dutch isolated population<br />
I. V. Zorkoltseva 1 , T. I. Axenovich 1 , C. M. van Duijn 2 ;<br />
1 Institute <strong>of</strong> Cytology and <strong>Genetics</strong>, Novosibirsk, Russian Federation, 2 Department<br />
<strong>of</strong> Epidemiology & Biostatistics, Erasmus MC, Rotterdam, Netherlands.<br />
We analysed a large complex pedigree from a Dutch genetically isolated<br />
population . About 2600 <strong>of</strong> 19700 pedigree members were phenotyped<br />
and genotyped for autosomal 5208 SNPs (Illumina 6K linkage<br />
panel) . Complex segregation analysis <strong>of</strong> adult height was performed<br />
under mixed model including effects <strong>of</strong> biallelic major gene, polygene,<br />
age and sex . We used likelihood approximation based on breaking<br />
pedigree loops. The results confirmed large contribution <strong>of</strong> genes in<br />
the trait variance (h 2 = 0.85 ) and significance <strong>of</strong> major gene effect<br />
in accordance with Elston-Stewart test . Three genotypic means were<br />
estimated as 183 .5, 178 .3 and 174 .6 cm in males at 40 years with<br />
average difference <strong>of</strong> male and female genotypic means about 13 cm .<br />
The putative major gene explained 18% <strong>of</strong> trait variance .<br />
A genome-wide scan was performed by variance-components method<br />
using Merlin program . Prior to analysis, the pedigree was split into<br />
smaller non-overlapping fragments, with maximum bit-size <strong>of</strong> 18 . No<br />
loci demonstrated significant linkage, however for 6 loci linkage was<br />
suggestive:<br />
SNP Chr Position(cM) LodScore<br />
rs1993104 19 56 .9 2 .71<br />
rs1873191 18 44 .7 2 .60<br />
rs1019845 2 195 .8 2 .27<br />
rs958883 5 123 .3 2 .15<br />
rs936347 16 17 .2 2 .11<br />
rs216223 17 2 .1 2 .11<br />
Of these six loci, five were identified in previous linkage analyses, while locus at chromosome<br />
16 (rs936347) was new.
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