2009 Vienna - European Society of Human Genetics

Statistical genetics, includes Mapping, linkage and association methods
P08.34
comprehensive approach to investigate the genetic basis of
hereditary hearing loss in iranian population
H. Najmabadi 1 , C. Nishimura 2 , N. Meyer 2 , T. Yang 2 , N. Bazazzadegan 1 , Y. Riazalhosseini
1 , G. Asaadi Tehrani 1 , A. Daneshi 3 , M. Farhadi 3 , S. Yahyavi 1 , P. Imani 1 ,
A. Anousheh 1 , A. Nazeri 1 , K. Jalalvand 1 , M. Malekpour 1 , N. nikzat 1 , S. Arzhangi
1 , S. Azimi 1 , F. Larti 1 , Z. Fattahi 1 , M. Babanejad 1 , K. Kahrizi 1 , R. J. H. Smith 2 ;
1 Genetics Research Center, University of Social Welfare and Rehabilitation Sciences,
Tehran, Islamic Republic of Iran, 2 Molecular Otolaryngology Research
Laboratories, Department of Otolaryngology, University of Iowa, IA, United
States, 3 Research Center of Ear, Nose, Throat, and Head and Neck Surgery,
Iran university of Medical sciences, Tehran, Islamic Republic of Iran.
Genetic testing for deafness in Iran is well established. The population
is extremely heterogeneous, which means that ethnic-specific data are
required. We have generated much of these data by screening over
2000 families segregating autosomal recessive non-syndromic deafness
(ARNSD). All patients were screened for mutations in GJB2 and
GJB6 (DFNB1), and if no mutations were identified, haplotypes were
reconstructed by typing three short tandem repeat polymorphisms
flanking 22 known ARNSD loci. In a subset of families, genome-wide
linkage analysis was completed. Our data show that 16.7% of the
Iranian population with ARNSHL segregates mutations in GJB2. The
most prevalent mutation in this gene was 35delG, although 34 different
mutations have been identified of which seven are common. We have
also identified a novel GJB2 mutation in an endogenous population
segregating ADNSHL in village in northern Iran. In approximately 30%
of families, we have been able to establish a genetic cause for deafness.
Over half have mutations in GJB2, and followed by mutations
in SLC26A4, TECTA and USH1C . We have also found mutations in
PJVK, TMC1, USH1C, OTOF, MYOVIIA and VLGR1. Lastly, we have
described a new syndrome, a contiguous gene deletion syndrome that
involves both deafness and infertility in males (DIM Syndrome). These
data from the Iranian population attest to its diversity and contribute to
the current body of knowledge regarding the deafness of genetics.
P08.35
Evidence for genetic heterogeneity of bipolar disorder according
to age at onset in 2q14
M. Dizier 1 , F. Mathieu 2 , European Collaborative Study of Early-Onset BPAD;
1 INSERMU535, Villejuif, France, 2 INSERMU955, Créteil, France.
The aim of the present study is to perform a fine mapping of 8 regions
previously identified by a genome-wide linkage analysis in European
families ascertained through an early onset bipolar affective disorder
(BPAD) type I proband (Etain et al., 2006). Early age at onset was defined
as an age at first thymic episode below 21 years. The initial sample
of 70 families was extended to 120. Probands were early onset bipolar
type I patients and affected sibling were either early onset BPAD
type I patients, later onset of BPAD type I or early onset BPAD type II).
Since presence of genetic heterogeneity of BPAD may exist according
to the phenotypic heterogeneity of siblings, the Predivided Sample
Test and the Maximum Likelihood Binomial methods were used to test
genetic heterogeneity using 138 independent affected sib-pairs. Of
the 8 regions of linkage suggested by our previous genome scan, six
regions (2q14, 3p14, 5q33, 7q36 16p23 and 20p12) remained linked
to BPAD. Regions (2p21 and 10q23) were not confirmed. A genetic
heterogeneity was revealed between early and late onset BPAD type I
in the 2q14 region (p=0.0001) using the two methods. For BPADI sibpairs
concordant for early age at onset, parental allele sharing proportion
is higher (0.58) than for discordant pairs for age at onset, i.e. late
onset BPADI (0.28). All these results show for the first time the underlying
genetic heterogeneity in bipolar affective disorder and validate the
age at onset as a relevant factor in its genetic vulnerability.
P08.36
Frequency of single nucleotide polymorphisms in ABCG gene
in Japanese hyperuricemic patients
K. Ichida 1,2 , H. Matsuo 3 , N. Shinomiya 3 , T. Hosoya 2 ;
1 Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan, 2 Jikei University
School of Medicine, Tokyo, Japan, 3 National Defense Medical College,
Tokorozawa, Japan.
Gout is a heterogeneous diseases resulting from tissue deposition of
uric acid crystals, based on hyperuricemia. Uric acid is the end product
of human purine metabolism and serum uric acid concentration
is determined by the balance between production and elimination.
The kidney plays a main role in uric acid elimination. The transporters
for uric acid have been identified such as URAT1, OAT1, OAT3
and MRP4. Several recent genome-wide association studies identified
associations between single nucleotide polymorphisms (SNPs) in the
other transporter genes, SLC2A9, SLC17A3 and ABCG2, and serum
uric acid concentration and gout. For evaluation of influence of ABCG2
on serum uric acid concentration, we identified the frequency of SNPs
in ABCG2 gene of 198 Japanese hyperuricemic patients. As a result,
the frequency of some SNPs has been higher than that of Japanese
population. It suggests that the functional variation of ABCG2 due to
the SNPs influences serum uric acid concentration.
P08.37
Allele frequency of two autosomal stR loci FGA and D7s820 in
iranian population
M. Sharafi Farzad1 , S. Kiyanfar1 , Z. Shahab Movahed1 , S. Mousavi1 , S. Zeinali2
;
1 2 Kawsar Genomics Research Center, Tehran, Islamic Republic of Iran, Pasteur
institute of Iran, Tehran, Islamic Republic of Iran.
Short tandem repeat (STR) genetic loci were assigned for use in forensic
investigation. Allele frequency of two autosomal STR loci FGA and
D7S820 were determined in Iranian population.
DNA from 579 or 556 unrelated individuals were analyzed for D7S820
and FGA markers respectively. Extracted DNA were amplified by using
AmpF STR Identifiler Kit and 3130 Genetic Analyzer from ABI
(US). Allele frequencies and forensic efficiency parameters such as
Heterozygosity (H), Polymorphism Information Content (PIC), Power
of Discrimination (PD), Propability of Match (PM), Power of Exclusion
(PE), and typical Paternity Index (PI), were calculated using the PowerstatsV12.xls
software (Promega, US).
A total of 11 alleles for D7S820 and 13 alleles and 9 iteralleles for FGA
could be observed. In the case of FGA, allele 23 showed the highest
frequency (18.2%) and alleles 16, 28 and interalleles 18.2, 31.2
had the lowest frequencies (0.1%). Allele range in FGA was from 16
to 31.2 repeats with lower match propability (MP=0.034) compared
with D7S820 (MP=0.066). In D7S820 marker the highest frequency
(25.9%) was belonged to allele 11 and the lowest frequencies (0.1%)
were found to be for repeats 29, 30. Also the highest PD (0.966) and
PE (0.658) belonged to FGA. We also observed several interalleles for
FGA marker. But there was not any evidence of interalleles for D7S820
locus.The results indicated that the both loci were in Hardy-Weinberg
equilibrium.
P08.38
A genetic study of the VWA and tHO1 short tandem repeat
systems in iranian population
S. M. Z. S. Kiyanfar, S. Kiyanfar;
Kawsar Genomics Research Center, Tehran, Islamic Republic of Iran.
Several STR markers have been investigated to be routinely used for
forensic purposes. Allele frequencies of the two short tandem repeats
(STRs) namely VWA and THO1 were determined in Iranian population.
DNA from 573 or 596 unrelated individuals were analyzed for
THO1 and VWA markers respectively. Extracted DNA were amplified
by using AmpF STR Identifiler Kit and 3130 Genetic Analyzer from ABI
(US). Allele frequencies and forensic efficiency parameters such as
Heterozygosity (H), Polymorphism Information Content (PIC), Power
of Discrimination (PD), Propability of Match (PM), Power of Exclusion
(PE), and typical Paternity Index (PI), were calculated using the PowerstatsV12.xls
software (Promega, US).
A total of 16 alleles for VWA and 16 alleles for THO1 could be observed.
In the case of VWA, allele 17 showed the highest frequency and alleles
8, 9, 9.3, 10,11,12,15.2 had the lowest frequencies. Allele range was
from 8 to 20 repeats with higher match propability (MP=0.083) compared
with THO1.
In THO1 marker the highest frequency was belonged to allele 6 and
the lowest frequencies were found to be for repeats 5,13,17. Also the
highest PD and PE belonged to THO1. We also observed several interalleles
for both markers. In this study both loci provided allelic frequencies
of high heterogeneity to use them for forensic and related
purposes.