2008 Barcelona - European Society of Human Genetics

Normal variation, population genetics, genetic epidemiology
P07.089
Population genetics study of three microsatellite markers
(D3s1358, tH01 and FGA) in two Romanian groups and their
genetic relationships to European populations
A. Rodewald 1 , A. Kroll 1 , G. Cardos 2,3 , C. Tesio 3 , C. Tesio 3 , D. Banica 4 ;
1 Depatment of Human Biology of University, Hamburg, Germany, 2 ”Victor
Babes” National Institute, Bucharest, Romania, 3 Faculty of Biology, University
of Bucharest, Bucharest, Romania, 4 ”Marius Nasta” Institute of Pulmonary Diseases,
Bucharest, Romania.
In this study three different DNA-Microsatellites (D3S1538, TH01 and
FGA) have been analysed in a sample of 200 individuals from the
Romanian capital Bucharest; this data was compared with the data
from a sample of 110 individuals from Prahova Valley (Carpathian
Mountains) and with other European, Asian and African populations .
Further, we investigated the possible extent of genetic influences by
migrations of European neighbour populations on the Romanian genetic
pool .
The results reveal that there were not any significant differences in the
allele frequencies from the three microsatellite markers between the
panmictic population of Bucharest and the slight isolated population
from Prahova Valley .
Genetic distance analysis showed a close genetic relationship with
Greek population as well as Slavic populations from Poland and Slovenia
.
Historically this could be the result of intense trading activities of old
Thracian and Daco-Gethic tribal groups from Romanian territory and
Greek population groups, who established trading colonies at the west
coast of the Black Sea (actually East-Romania) during the 6th-8th century.
The Slavic influence is thought to be the result of the migrations of
Slavic groups in the 6th-9th century across the Danube and Carpathian
regions .
The study showed a more significant genetic distance from Romanian
populations to the Croatian, Austrian, Hungarian and German populations
.
This data can also be used for paternity and forensic analyses in the
Romanian population .
P07.090
Evolutionary process of disease-associated oligonucleotide
repeats until their expansion in humans
S. Martins 1 , V. C. N. Wong 2 , P. Coutinho 3 , J. Sequeiros 4,5 , A. Amorim 1,6 ;
1 IPATIMUP, Porto, Portugal, 2 Dept Paediatrics and Adolescent Medicine, The
Univ of Hong-Kong, Hong-Kong, China, 3 Hosp S Sebastião, Santa Maria da
Feira, Portugal, 4 IBMC- Instituto de Biologia Molecular e Celular, Porto, Portugal,
5 ICBAS, Porto, Portugal, 6 Fac Ciências, Univ Porto, Porto, Portugal.
More than 40 neurological and neuromuscular disorders have been
identified as caused by the expansion of repetitive sequences. The
study of these loci over an evolutionary timescale becomes especially
relevant to understand better the mechanisms behind these humanspecific
pathogenic expansions. In a previous study of the ATXN3 locus,
responsible for Machado-Joseph disease, we found evidence for
an alternative, multi-step mechanism promoting allelic variation within
the normal range, either by slippage replication of multiple CAGs or
gene conversion . To gain insight into the wild-type alleles that might
have been involved in the expansion process, we have now compared
the flanking STR-backgrounds of different normal-sized alleles
with the ancestral expanded haplotypes from the same SNP-based
lineage, in 67 MJD families (42 from the GTGGCA and 25 from the
TTACAC haplotypes), analysed as before . Pairwise comparisons did
not show a direct correlation between the size of wild-type haplotypes
and its genetic distance to expanded alleles . For lineage TTACAC, the
genetic background of expanded alleles was identical to those with 20
and 28 CAGs (R ST =0); for GTGGCA, a close relationship was found
between expanded chromosomes and (CAG) 23 and (CAG) 27 alleles .
These results led us to propose the possibility of a multi-step mutational
mechanism, underlying also the process of de novo expansions in
MJD . Assuming that similar mechanisms may be driving other repetitive
tracts, we plan to study the evolutionary dynamics at the ATXN1,
DRPLA, ATXN7, KLHL1AS, PPP2R2B, TBP, and FMR1 loci . Selection
was based on different allelic distribution, consensus motif and repeat
configuration.
P07.091
On the epidemiology of the MTHFR-c677t gene variant in
mexico: A multiregional and multiethnic study
O. M. Mutchinick, M. A. López, B. E. Sánchez;
Instituto Nacional de Ciencias Médicas y Nutrición, México, D.F., Mexico.
It is well known the worldwide prevalence differences of the MTHFR
gene C677T variant . Also is well known that the homozygous for the T
allele, produce a deficient metylenetetrahidrofolate reductase enzyme
with less than 50% activity, being this considered a risk factor for some
birth defects, cardiovascular disease, thrombosis and cancer, among
other health problems . In 1999 we reported a very high T allele prevalence
in adult healthy Mexican female sample .
Herein we report the allelic and genotypic prevalence of the MTHFR-
C677T variant found in 800 healthy newborns (HNB) from eight different
provinces of the North, East, West, Centre and South and 440
indigenous people from five different ethnic groups (DEG) of the country
.
In HNB the T allele prevalence and TT genotype range from 0 .37%
to as high as 0 .71% and from 17 .0% to 52 .0% respectively, with a
clear North to Southeast increasing gradient . In the DEG, remarkable
differences were also observed, with the lower T allele (0 .58%) and
TT genotype (33 .3%) prevalence in Tojolabales Indians, to the highest
prevalence of 0 .81% and 68 .6%, in the Mazateco ethnic group .
The same was observed when HNB from distinct provinces were
compared . All groups studied were in Hardy-Weinberg equilibrium .
The higher prevalence of the T allele in HNB in the Southeast provinces
concurs with the natural setting of the ethnic groups studied .
Our findings suggest that the very high prevalence of the T allele and
TT genotype observed may be the result of inbreeding and advantage
selection of the variant .
P07.092
mutation 35delG and m34t screening in GJB (connexin 26
gene) in Estonian population
R. Teek1,2 , T. Temberg2 , M. Kõiv2 , E. Raukas2 , N. Tõnisson2 , M. Kull1 , K. Õunap2,3
;
1Department of Oto-Rhino-Laryngology, University of Tartu, Tartu, Estonia,
2Department of Genetics, United Laboratories, Tartu University Hospital, Tartu,
Estonia, 3Department of Pediatrics, University of Tartu, Tartu, Estonia.
Hearing loss is the most common sensory disorder worldwide . Mutations
in GJB2 (connexin 26) gene are a major cause of autosomal-recessive
non-syndromic hearing loss in Caucasian population . Mutation
35delG in this gene is the most common cause for early onset hearing
loss. The purpose of our study was to find out the carrier frequency of
35delG and M34T mutation among Estonian population .
We have screened 524 consecutively born neonates (the investigation
is planned for up to 1000 newborns born in one month in whole Estonia)
. Our study uses anonymous random samples of dried blood spots
on Guthrie cards from mass newborn screening program . We’ve found
one homozygote and 29 heterozygotes for 35delG mutation . We’ve
also detected 31 heterozygotes for M34T mutation, but no M34T homozygote
so far . The carrier frequency for 35delG was 1 in 18 and 1
in 17 for M34T . The theoretical incidence of homozygotes for 35delG
is 1:1296 and 1:1156 for M34T . Previous studies have shown 1 in 35
35delG carrier frequency in South-Europe, 1 in 79 Central and Northern
Europe, and 1 in 22,5 in Estonia on 113 samples only (Gasparini et
al., 2000) . Our study shows similarly the high carrier frequency of mutation
35delG among Estonian newborns . The incidence of mutation
M34T is similar to mutation 35delG and it correlates well with results of
our patients with early onset hearing loss . M34T is the second frequent
mutation in our patient group .
This work was supported by grant GARLA 6808 from the Estonian
Science Foundation .
P07.093
Physiological splicing variants in the NiPBL gene
B. Puisac, M. Ciero, M. C. Gil, M. Arnedo, M. P. Ribate, J. C. de Karam, J.
Gomes, S. Menao, A. Pie, F. J. Ramos, J. Pie;
University of Zaragoza Medical School, Zaragoza, Spain.
Mutations in a regulator of the cohesin complex, the NIPBL gene, located
in 5p13 .1, are responsible for Cornelia de Lange Syndrome 1
(CDLS1, MIM 122470) . CdLS is an inherited multisystem developmental
disorder characterized by distinctive dysmorphic facial features,