2008 Barcelona - European Society of Human Genetics

Genomics, technology, bioinformatics
of the genetic models underlying the trait . Prior knowledge of the genetic
structure of the isolate is therefore a fundamental prerequisite for
designing and carrying out successful association studies of complex
disorders .
Sardinians has long been the object of study by geneticists by virtue of
their ancient origin and long-standing isolation . Some studies suggest
that the Sardinians are a relatively homogenous population with no
significant heterogeneity among sub-regions. These reports are however
in contradiction with several others demonstrating the existence
of differentiated sub-regions, molded by natural, cultural barriers and
historical events .
Our aim is to determine the extent of homogeneity in the Central-Eastern
Sardinia that includes the archaic area as defined by archeological,
linguistics and genetic studies . We determined Y-chromosome lineages
in 256 unrelated Sardinian males from this area using a panel
of informative biallelic markers (SNPs) and microsatellite (STRs) . In
addition to sex-specific markers we also used autosomal SNPs (500K
Affymetrix chips) in 100 of the DNA samples to determine accurately
kinship values .
Our analysis shows that the frequency of the major Y haplogroups
clearly sets this population apart from the rest of the Europeans haplogroups
.
Our results allow to evaluate how past peopling and demographic
events might impact genome wide association study design for complex
disorders that show a high incidence or a founder effect in this
part of the island such as Diabetes type-1 and Breast-cancer .
P07.139
caracterization of the mitochondrial haplogroups of two
Andean populations (Aymaras and Quechuas) from the Bolivian
Altiplano: comparison to other south-American populations
M. Gayà-Vidal 1 , N. Saenz 2 , A. Sevin 2 , C. Coudray 2 , C. Thèves 2 , G. Athanasiadis
1 , E. Esteban 1 , M. Villena 3 , A. Rodriguez 3 , R. Vasquez 3 , J. M. Dugoujon 2 , P.
Moral 1 ;
1 Unitat d’Antropologia, Dpt. de Biologia Animal, Facultat de Biologia, Universitat
de Barcelona, Barcelona, Spain, 2 Centre d’Anthropologie UMR 8555 CNRS, Toulouse,
France, 3 IBBA, La Paz, Bolivia.
Mitochondrial DNA has been widely used in human population genetic
studies . It has been used to treat the colonization process of the New
World . Particularly, in South-America, the Andean region with its geographic,
environmental and historical particularities is an important
area for these studies .
We have analyzed the mitochondrial DNA diversity of two Amerindian
populations from the Andean Altiplano belonging to the two main Amerindian
linguistic groups in Bolivia, namely Aymaras and Quechuas .
The Aymara population is situated between La Paz and the Titicaca
Lake and the Quechua population located in the Potosi department .
Our aim is to provide new mtDNA data from these two Andean Altiplano
populations .
Haplogroup (A, B, C, and D) and sub-haplogroup determinations have
been carried out through RFLP analysis in the coding region, as well
as through DNA sequencing of the HVI and HVII regions (16020-250)
in 190 non-related individuals .
After the determinations, the allele frequencies have been calculated
and compared to other South-American populations for which data are
available in the literature . Statistical analyses have been carried out in
order to assess the genetic relationships between just the two populations
of this study and also regarding three geographical levels: South-
America, Central Andes and Bolivia .
P08. Genomics, technology, bioinformatics
P08.01
DEciPHER (DatabasE of chromosomal imbalance and
Phenotype in Humans using Ensembl Resources) - http://
decipher.sanger.ac.uk
S. M. Richards 1 , R. M. Pettett 1 , P. A. Bevan 1 , S. Van Vooren 1 , H. Fiegler 1 , H. V.
Firth 2 , N. P. Carter 1 ;
1 Wellcome Trust Sanger Institute, Cambridgeshire, United Kingdom, 2 Cambridge
University Dept of Medical Genetics, Addenbrooke’s Hospital, Cambridge,
United Kingdom.
DECIPHER is a web-based, interactive database which provides a link
between phenotype and chromosomal rearrangement utilising the En-
sembl genome browser and other bioinformatics resources .
DECIPHER provides the architecture for international collaborative effort
identifying new syndromes and genes involved in human development
and disease, forinterpreting array CGH data and improving medical
care for patients with congenital abnormalities . The DECIPHER
Consortium has grown considerably over the last four years with database
entries of over 1500 patients from approximately 90 centres
worldwide .
In DECIPHER, molecularly defined rearrangements (e.g. from array-
CGH) are mapped on to the reference sequence for viewing in Ensembl.
Genes within the affected region are identified and prioritised
according to their relevance to the phenotype . Clusters of rearrangements
within the same region in patients with comparable phenotypes
enable new syndromes to be defined and published.
Other features in DECIPHER which aid in the interpretation of microarray
data include:
Trio analysis tool - A trio of an affected individual and parents are analysed
to determine de novo or familial/inherited conditions .
Gene prioritisation tool - advanced text mining searches PubMed for
associations between highlighted genes and phenotypes .
Search tool - a search engine for ‘consented’ data within DECIPHER to
facilitate the identification of rearrangement clusters and links between
phenotype and genomic location .
DECIPHER enables international collaborative research on developmental
disorders and provides a powerful knowledge base for clinical
diagnosis and management of patients with congenital abnormalities .
P08.02
3c on FOXL .
D. Beysen 1 , J. Dostie 2 , B. D’haene 1 , A. De Paepe 1 , J. Dekker 2 , E. De Baere 1 ;
1 Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium, 2 Program
in Gene Function and Expression, University of Massachusetts Medical
School, Worcester, MA, United States.
Defective long distance gene regulation is an emerging mechanism
underlying human disease . Blepharophimosis syndrome (BPES), an
autosomal dominant condition affecting eyelid and ovary development,
is caused by mutations in the FOXL2 gene . Its expression is strictly
regulated, which was illustrated by the recent identification of deletions
upstream and downstream of its transcription unit as underlying cause
of BPES . We demonstrated that these rearrangements remove several
conserved non-coding sequences (CNCs) harbouring potential
long-range cis-regulatory elements .
Here, we used Chromosome Conformation Capture (3C) to identify
long-range interactions of cis-regulatory elements with the FOXL2 promoter
in two adult FOXL2 expressing cellular systems . We found that
in adult ovarian granulosa cells and fibroblasts three long-range cisregulatory
sequences located 177 kb, 283 kb and 360 kb upstream of
FOXL2 come in close vicinity to the FOXL2 core promoter . Noteworthy,
3C in human fibroblasts derived from a BPES patient with a heterozygous
deletion of the region encompassing the regulatory element at
283 kb, revealed decrease of interaction of the deleted element and
the FOXL2 core promoter and the two other regulatory elements . Interestingly,
the element at 283 kb corresponds to a sequence deleted
in the Polled Intersex (PIS) goat, which is an animal model for BPES .
In conclusion, we hypothesize that the interaction between the cisregulatory
element located at 283 kb and the FOXL2 core promoter
is essential to establish efficient transcriptional regulation of FOXL2
expression .
P08.03
study of the antisense transcript to AFAP1 human gene
A. V. Marakhonov 1 , A. Baranova 1,2 , T. Kazubskaya 3 , S. Shigeev 4 , M. Y. Skoblov
1 ;
1 Research Centre for Medical Genetics, Russian Academy of Medical Sciences,
Moscow, Russian Federation, 2 Molecular and Microbiology Department,
College of Science, George Mason University, Fairfax, VA, United States,
3 Blokhin Cancer Research Centre, Russian Academy of Medical Sciences,
Moscow, Russian Federation, 4 Department of Forensic Medicine, Faculty of
Medicine, People’s Friendship University of Russia, Moscow, Russian Federation.
Antisense regulation of gene expression is a widespread but not wellunderstood
mechanism of gene expression regulation . Recently we
have carried out a whole genome in silico search of cis-antisense