2008 Barcelona - European Society of Human Genetics

Concurrent Sessions
c13.5
the genetic control of microRNA expression variation in
Humans
C. Borel, S. Deutsch, H. Attar, M. Gagnebin, C. Gehrig, E. Falconnet, Y. Dupré,
S. E. Antonarakis;
Department of Genetic Medicine and Development, University of Geneva Medical
School, CH, Geneva, Switzerland.
C .B . and S .D . contributed equally to this work .
MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate
the expression of protein-coding . Each miRNA is thought to have
multiple target genes that are regulated at the post-transcriptional
level .Inter-individual variation of miRNA gene expression is likely to
influence the levels of target genes, and may therefore contribute to
some phenotypic differences, including susceptibility to common disorders
. The aim of this study was to characterize the natural variation in
miRNA expression levels present in different individuals, and to identify
loci that control this variation .
We established primary fibroblasts from 200 unrelated umbilical cord
samples of Caucasian origin (GenCord collection) .All of these samples
have been genotyped using the Illumina Hap550 SNP array . After multiple
filtering steps 433’000 were retained for statistical analyses. Taqman
real-time PCR in all cell lines was used to measure the expression
of 365 known mature microRNAs in each sample . This revealed
substantial differences in miRNA expression levels between individuals,
which were up to 50-fold in some cases . Normalized miRNA levels
for each individual were used to perform quantitative whole genome
association studies using the Plink software . We will present the detailed
genome-wide association analysis of SNPs that control in cis- or
trans- miRNA expression .
This is the first attempt to characterize the genetic regulation of miRNA
expression levels. Loci identified through this approach are likely to be
important determinants of human phenotypes .
c13.6
comparison of different methods to estimate genetic ancestry
and control for stratification in genome-wide association studies
E. Salvi 1,2 , G. Guffanti 1 , A. Orro 2 , F. Torri 1 , S. Lupoli 3 , J. Turner 4 , D. Keator 4 , J.
Fallon 4 , S. Potkin 4 , C. Barlassina 1 , D. Cusi 1 , L. Milanesi 2 , F. Macciardi 1 ;
1 Department of Science and Biomedical Technology, University of Milan, Milan,
Italy, 2 ITB CNR, Segrate, Milan, Italy, 3 INSPE, Milan, Italy, 4 Department of Psychiatry
and Human Behavior University of California, Irvine, CA, United States.
In case-control association studies, population subdivision or admixture
can lead to spurious associations between a phenotype and unlinked
candidate loci. Population stratification can occur in case-control
association studies when allele frequencies differ between cases
and controls because of ancestry .
We evaluated five methods (Fst, Genomic Control, STRUCTURE,
PLINK and EIGENSTRAT) using 317K SNPs (Illumina HumanHap300)
in a case-control sample of 200 American subjects with different races
(Caucasian, African and Asian) in order to identify and to correct for
stratification. Fst, Structure and Genomic Control are based on the
usage of few genetic markers while PLINK and EIGENSTRAT are
computationally tractable on a genome-wide scale . Fst, STRUCTURE
and Genomic Control did not detect a significant stratification in our
sample, as well as EIGENSTRAT and PLINK . However, these last two
methods, using a much larger information from the whole set of SNPs,
graphically suggested the presence of a partial stratification, due to
African and Asian individuals while the estimated inflation factor of 1
didn’t statistically confirm stratification. This brought to the decision to
further enlarge the sample with hundreds of controls coming from Caucasian
populations . When we enlarged the sample to 650 individuals
we found a high value of inflation factor as statistical confirmation of
the population stratification. The substructure still depends only on African
and Asian subjects that are separated from the Caucasian homogeneous
sample . Therefore the sample size is crucial to get enough
power to detect a possible stratification.
c14.1
the ethics of undertaking research in other countries
L. Skene;
University of Melbourne, University of Melbourne, Australia.
There are many reasons for scientists to undertake research with colleagues
in other countries: to share knowledge and experience with
colleagues; to obtain funding directed to transnational projects; to gain
access to facilities and research participants; to acquire kudos, academic
advancement, or commercial benefits; or to undertake activities
that would not be permitted in their own country, due to legal or ethical
constraints .
This paper considers the last reason and when it is ethical for scientists
to do research abroad that is banned at home . The author argues
that such research may sometimes be ethical, provided it is scientifically
rigorous and accords with international ethical principles and
ethical oversight requirements . But it is not ethical when the proposed
research is widely regarded as unethical in the home country . The author
uses her own image of Skene’s Ethico-Legal Barometer to gauge
the activities that attract this degree of sensitivity and would be unethical
wherever they are done . This research is in the red zone of the barometer
and the closer an activity falls to the red zone, the greater the
need for ethical review and oversight before being ethically acceptable
in the home country .
The author illustrates these arguments with examples like human embryonic
stem cell research, somatic cell nuclear transfer and research
involving human subjects .
c14.2
Direct-to-consumer services. A review of the debate
P. Borry;
Centre for Biomedical Ethics and Law, Leuven, Belgium.
Background . The rapid expansion of the internet has meant that there
is now a global marketplace for a multitude of health care products and
services that are available directly to the consumer . Related to this, in
the field of genetics, the rapid expansion of knowledge about the relationship
between genetics and human disease has set the groundwork
for commercial enterprises that use direct-to-consumer (DTC) advertising
for genetic tests and, in some cases, bypass the supervision
of a health professional to offer DTC purchase of the tests . Various
companies (e .g . Sciona (UK), DNA direct (US), Genelink (US), Test
Kimball Genetics (US), Geneticom (The Netherlands)…) have been
identified where direct-to-consumer tests are offered (e.g. for paternity
testing, ancestry testing, susceptibility tests for cardiovascular diseases,
hereditary hemocromatosis, osteoporosis, Factor V Leiden, type 2
diabetes…) .
Objective . This paper wants to investigate the existing ethical and legal
framework of direct-to-consumer services .
Method . It will offer a review of the debate through a systematic analysis
of the position papers, reports, guidelines or statements emanating
from international and national organisations, bioethics committees,
and professional associations, together with the academic literature
identified after an extensive literature search.
Results. This paper offers an overview of the debate. It identified weaknesses
in the existing regulatory framework and suggested further
pathways for research .
c14.3
Preventive genetic screening in the isolated community: lessons
learned
L. Basel-Vanagaite 1,2 , E. Taub 3 , L. Rainshtein 3 , V. Drasinover 3 , N. Magal 3 , J.
Zlotogora 4 , M. Shohat 3 ;
1 SCMCI and Rabin Medical Center, Petah Tikva, Israel, 2 Tel Aviv University, Tel
Aviv, Israel, 3 Rabin Medical Center, Petah Tikva, Israel, 4 Department of Community
Genetics, Ministry of Health and Hadassah Medical School Hebrew
University, Jerusalem, Israel, Tel Hashomer, Israel.
In the countries with high rates of consanguinity, many inherited diseases
are present with a high frequency only in a limited geographical
region . We present a comprehensive strategy for genetic diseases
prevention program in the isolated community in Israel and examine
the impact of the screening on the population .
During years 2003-2007, we carried out carrier screening among the
residents of an isolated village of 10,500 inhabitants with a high frequency
of non-syndromic mental retardation (MRT3), spinal muscular
atrophy, spinal muscular atrophy with respiratory distress and cystic
fibrosis. The subjects were pregnant women visiting the women’s
health station for routine monitoring . The medical geneticist or genetic
counselor provided counseling . A three-generation pedigree was constructed
by interviewing the women and the nurses . The screening was
provided free of charge, financed by the Israeli Ministry of Health . We