2008 Barcelona - European Society of Human Genetics

Molecular and biochemical basis of disease
vLINCL but also in NCL patients with later onset and a more protracted
disease course .
P06.208
Linkage analysis in 238 ADHD-families identifies genome-wide
significant signals on chromosomes 2q21.1 and 13q12.11 for
neuropsychological measures
N. N. J. Rommelse 1 , A. Arias-Vásquez 2 , M. E. Altink 3 , C. J. M. Buschgens 3 ,
E. Fliers 3 , S. V. Faraone 4 , J. K. Buitelaar 3 , J. A. Sergeant 1 , J. Oosterlaan 1 , B.
Franke 5 ;
1 Department of Clinical Neuropsychology, VU University, Amsterdam, The
Netherlands, 2 Departments of Psychiatry, Human Genetics and Epidemiology &
Biostatistics, Radboud University Medical Center, Nijmegen, The Netherlands,
3 Departments of Psychiatry, Radboud University Medical Center, Nijmegen,
The Netherlands, 4 Departments of Psychiatry and Neuroscience & Physiology,
SUNY Upstate Medical University, New York, NY, United States, 5 Departments
of Psychiatry and Human Genetics, Radboud University Medical Center, Nijmegen,
The Netherlands.
ADHD linkage studies have not revealed consistent findings, suggesting
alternative approaches to find genes involved in this disease. Endophenotypes,
defined as heritable, continuously distributed traits that
increase the risk for ADHD, may be more suitable for linkage analysis:
Endophenotypes seem less genetically complex than clinical disease
phenotypes . Moreover, they are often quantitative traits rather than
dichotomous entities (like DSM diagnostic categories), hence the
more powerful Quantitative Trait Loci (QTL) linkage analysis may be
applied . Genome-wide linkage analysis was performed in the Dutch
subsample of the International Multi-centre ADHD Genetics (IMAGE)
study encompassing 238 DSM-IV combined type ADHD probands and
their 112 affected and 195 non-affected siblings . Ten neuropsychological
measures (cognitive and motor measures) previously shown
to be candidate ADHD endophenotypes were used as quantitative
traits . In addition, an overall component score of neuropsychological
functioning was used, on which all ten individual measures related . A
total number of 5,407 autosomal SNPs were used to run a multipoint
regression-based linkage analysis. Two genome-wide significant linkage
peaks were found, one for Motor Timing on chromosome 2q21 .1
(LOD score: 3 .944) and one for Digit Span on 13q12 .11 (LOD score:
3.959). Eleven suggestive linkage peaks were found (LOD scores ≥ 2)
on chromosomes 2p, 2q, 3p, 4q, 8q, 9p, 12p, 12q, 14q, 17q . The suggestive
linkage signal of the component score at 2q14 .3 (LOD score:
2 .878) overlapped with the region linking to Motor Timing . In conclusion,
our results suggest that neuropsychological candidate ADHD-endophenotypes
may aid in the discovery of novel ADHD genes through
linkage analysis
P06.209
NFAtc4 gene polymorphism and aerobic performance in
athletes
D. V. Popov 1 , I. I. Ahmetov 2 , J. V. Shikhova 2 , S. S. Missina 1 , O. L. Vinogradova
1 , V. A. Rogozkin 2 ;
1 SRC Institute for Biomedical Problems of the Russian Acad. Sci., Moscow,
Russian Federation, 2 St Petersburg Research Institute of Physical Culture, St
Petersburg, Russian Federation.
Nuclear factor of activated T cells C4 gene (NFATC4) encodes transcription
factor which regulates cardiac and skeletal muscle metabolism .
The aim of the study was to investigate allelic distribution of NFATC4
gene Gly160Ala polymorphism in endurance-oriented athletes (n=549)
and controls (n=1057), and to find interrelation between genotypes and
physiological parameters in rowers (n=90) . Genotyping was performed
by restriction fragment length polymorphism analysis . Physiological
parameters were evaluated by PM 3 Rower Ergometer and MetaMax
3B Gas Analyzer. The frequency of NFATC4 Gly allele was significantly
higher in athletes than in controls (51 .5% vs . 43 .7%; p