2008 Barcelona - European Society of Human Genetics

Normal variation, population genetics, genetic epidemiology
P07.102
comparative studying of polymorphism 3`UtR genes-candidates
multifactor diseases in the siberian populations
N. P. Babushkina, L. A. Koneva, A. A. Rudko, E. Y. Bragina, A. N. Kucher, V.
P. Puzyrev;
Institute of Medical Genetics, Tomsk, Russian Federation.
Polymorphisms in 3`UTR in TNFAR (rs36188382), IL4RA (rs2074570),
IL12B (rs3212227), IL12RB1 (rs3746190) and IL12A (rs568408) have
been studied in several Siberian populations (Russians, Buryats, Tuvinians,
Yakuts, 383 individuals in total) . Deletion in 3`UTR gene TN-
FAR has not been revealed in all investigated groups . This can suggest
that the deletion has either very low polymorphism level, or it is
a mutation . For other loci, Hardy-Weinberg equilibrium was observed
for all genes except IL12A (rs568408) in Buryats (heterozygotes excess)
. Russians vs all other (Mongoloid) ethnic groups have shown
significant differences in allele frequencies of three SNPs: in Russians,
minor allele frequencies were 0 .042, 0 .229, 0 .189 for IL4RA, IL12A,
IL12B accordingly, where as in Buryats they were 0 .105, 0 .195, 0 .380;
in Tuvinians 0 .109, 0 .292, 0 .359; in Yakuts 0 .177, 0 .174, 0 .286 . The
maximum difference was observed between Russians and Yakuts and
minimum difference was between Tuvinians and Buryats . In contrast,
locus IL12RB1 (rs3746190) has shown maximum differences between
Tuvinians and Buryats (minor allele frequency 0 .495 and 0 .274 accordingly)
. This is additional evidence once again about complex ethnogeny
and different contributions of European and Asian components
in their gene pools .
P07.103
the analysis of cFtR mutation frequencies in different
populations of Russia
N. V. Petrova, E. E. Timkovskaya, R. A. Zinchenko;
Research Center for Medical Genetics, Moscow, Russian Federation.
3739 healthy donors from eight regions of European part of Russian
Federation were analyzed for seven CFTR mutations
(CFTRdele2,3(21kb), F508del, 1677delTA, 2143delT, 2184insA,
394delTT, 3821delT) accounted for 67% of CF alleles . 15 carriers
of F508del mutation, 1 carrier of CFTRdele2,3(21kb) mutation and
1 1677delTA carrier were identified in the samples of 1324 Russians
form Rostov, Tver, Pskov and Kirov provinces . Three F508del carriers
and one CFTRdele2,3(21kb) carrier were revealed among 780 Chuvashes
from Chuvashia, two F508del carriers - among 613 Udmurts
form Udmurtia and one CFTRdele2,3(21kb) carrier - in 517 Bashkirs
from Bashkortostan . In the sample of 505 Maris from Mary El none of
the analyzed CFTR mutations was found . The population frequency
of F508del mutation is 0,00525 (0,00401÷0,00676) in Russians from
European region, 0,00112 (0,00006÷0,00530) in Udmurts, 0,00192
(0,00052÷0,00496) in Chuvashs, low than 0,00458 in Bashkirs and low
than 0,00296 in Maris . The differences in F508del mutation frequencies
between Russians and Maries, Russians and Chuvashs, Russians
and Bashkirs are significant at 5% degree, between Russians
and Udmurts - at 10% degree .
P07.104
L162V polymorphism of PPAR-alpha gene in patients with
abdominal obesity
O. D. Belyaeva 1 , A. E. Garanina 1 , V. V. Ugolnikov 1 , O. A. Bercovich 1 , V. I. Larionova
2 ;
1 IP Pavlov State Medical University of Saint-Petersburg, Saint-Petersburg, Russian
Federation, 2 State Pediatric Medical Academy of Saint-Petersburg, Saint-
Petersburg, Russian Federation.
Aim . To evaluate the frequency of V162 allele of PPAR-a gene and determine
the distribution of L162V genotypes in patients with abdominal
obesity .
Methods . 26 males (BMI 30,58±0,80 kg/m2, waist circumference (WC)
105,56±2,23 cm), 53 females (BMI 30,28±0,59 kg/m2, WC 92,11±1,14
cm) entered the study (44,48±0,99 years) . Genotypes were determined
by polymerase chain reaction with subsequent restriction analysis . Biochemical
components were measured by enzymatic methods .
Results . Polymorphisms were determined in 79 participants . The V162
allele frequency was 0,076 . Plasma lipids, CRB, glucose, BMI and WC
did not differ in man and woman regardless of PPAR-a genotype (woman:
total cholesterol (tCh) 5,66±0,17, HDL 1,54±0,06 mmol/l, LDLP
3,80±0,17 mmol/l, TG 1,48±0,09 mmol/l, CRP 5,82±0,69 mg/l, glu-
cose 5,62±0,19, BMI 30,28±0,59 kg/m2, WC 92,11±1,14 cm; man: tCh
6,24±0,25 mmol/l, HDL 1,24±0,08 mmol/l, LDLP 4,13±0,25 mmol/l, TG
3,17±0,86 mmol/l, CRP 6,82±2,62 mg/l, glucose 6,41±0,51 mmol/l) .
Careers of V162 allele have higher tCh, LDLP and lower HDL values,
but the difference did not reach statistical significance. The V162
careers had higher glucose levels, but the difference did not reach
statistical significance (LL162 - 5,93 mmol/l, LV162 - 5,41 mmol/l, p >
0,05) . No difference between the genotypic groups was observed for
CRP(LL162: 6,24±1,05 mg/l; LV162: 4,69±1,40 mg/l; p > 0,05) .
Conclusion . The V162 allele frequency was 0,076, similar to that reported
in ischemic heart disease and diabetes mellitus patients and
healthy European man. No significant differences were observed between
the presence of V162 allele and changes in blood lipids, glucose
levels and body fatness measurements .
P07.105
minor CYP B involvement in the molecular basis of primary
congenital glaucoma in Bulgarian Gypsies
K. N. Kamenarova 1 , P. Sivadorai 2 , S. Cherninkova 3 , S. Bouwer 2 , D. Angelicheva
2 , P. Seeman 4 , K. Hollingsworth 5 , V. Mihaylova 6 , A. Oscar 3 , G. Dimitrova 3 ,
R. Kaneva 1 , I. Tournev 3 , L. Kalaydjieva 2 ;
1 Molecular Medicine Centre, Sofia, Bulgaria, 2 Centre for Medical Research and
WA Institute for Medical Research, The University of Western Australia, Perth,
Australia, 3 Department of Neurology and Department of Ophthalmology, Alexadrovska
Hospital, Medical University, Sofia, Bulgaria, 4 Department of Child
Neurology, 2nd School of Medicine, Charles University, Prague, Czech Republic,
5 Neurodegenerative Disorders Centre, Queen Elizabeth II Medical Centre,
Perth, Australia, 6 Department of Neurology, Alexadrovska Hospital, Medical
University, Sofia, Bulgaria.
Primary Congenital Glaucoma (PCG) is characterised by locus and allelic
heterogeneity . Mutations in the cytochrome P450 1B1 (CYP1B1)
gene contribute between 20-30% in cases from ethically mixed populations
and between 50-80% in populations where consanguinity is
common . The Roma/Gypsies are considered to be a rare example of a
founder CYP1B1 mutation, with E387K (identified in a Slovak Roma),
accounting for 100% of disease alleles . In the current study of 21
Gypsy PCG patients from Bulgaria and of 715 unscreened controls
from the general Gypsy population unusual genetic heterogeneity was
revealed . In the sample of affected subjects from 16 families, we identified
five different CYP1B1 mutations - four known (E229K, R368H,
E387K and R390C) and one novel and potentially pathogenic (F445I),
which together account for ~30% of disease alleles . Three of the mutations
have been previously found in PCG patients from India . E387K
was rare in both the patient and the control group (carrier rate 0 .56%),
indicating that its high frequency in the Slovak Roma is most likely a
product of local founder effect . Sequencing of MYOC and genotyping
polymorphisms linked to GLC3B and GLC3C did not support the involvement
of these loci, previously implicated in PCG pathogenesis .
The genetic basis of PCG in the Gypsies thus remains not completely
resolved .The characteristics of the Gypsies as a founder population
could facilitate the identification of novel unidentified PCG gene yet.
P07.106
Evaluation of a powerful screening tool for hereditary
prosopagnosia
I. Kennerknecht 1 , H. Wang 2 , T. Elze 3 , B. Welling 4 , V. Wong 5 , J. Liu 6 ;
1 Institute of Human Genetics, Westfälische Wilhelms-Universität Münster, Münster,
Germany, 2 Social Science Department, Chang Chun Taxation College,
Jilin, China, 3 Max Planck Institute for Mathematics in the Sciences, Leipzig,
Germany, 4 Institute of Human Genetics Westfälische Wilhelms-Universität Münster,
Münster, Germany, 5 Department of Paediatrics & Adolescent Medicine,
The University of Hong Kong, Queen Mary Hospital, Hong Kong, China, 6 State
Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University,
Beijing, China.
Prosopagnosia (PA) or face blindness is characterized by a highly selective
impairment in recognition of faces . Longest and best known
is the acquired form after e .g . brain injuries, strokes or atrophy of the
right-occipito-temporal cortex . Recently, we could show that (1) the
congenital form, in the absence of any traumatic event, is highly frequent,
with a prevalence of around 2% worldwide, that (2) it almost
always runs in families, and that (3) most surprisingly segregation
pattern is fully compatible with autosomal dominant inheritance . We
therefore coined the term hereditary PA (HPA, Kennerknecht et al .