A Swedish group is searching a consortium working with a proposal for the Topic: HEALTH.2010.2.4.5-1: Investigation of the mechanisms of initiation of allergic response, genetic predisposition, biomarkers and identification of targets for therapy.

Datum objave: 05.08.2009

Kategorija: Aktualno na Univerzi

The molecular basis of many complex traits, such as asthma, remains difficult to define and we take a novel approach to overcome the challenge. The DNA Copy Number Variation (CNV) is the most frequent type of human genetic variation. When comparing two unrelated subjects, the total amount of variation involving CNVs was higher than that for single-nucleotide polymorphisms (SNPs). Furthermore, the locus-specific mutation rate for CNVs has been suggested to be two to four orders of magnitude greater, than the corresponding number for SNPs. We have recently shown that monozygotic (MZ) twins frequently display within-pair differences in CNV profiles. The above indicates the feasibility of targeting cohorts of MZ twins, discordant for established phenotypes in search for de novo aberrations that predispose for a disease.

We will use well characterized cohort of MZ twins discordant for asthma, as the first common and complex disease to study using this approach. We will search for de novo somatic genetic and epigenetic aberrations that predispose for asthma and validate these on multiple levels in disease concordant MZ twins as well as in single born population affected by asthma. Furthermore, we will develop a new technology for more efficient CNV discovery and validation. We will also create novel in vitro resources, useful for functional asthma studies, including the establishment of induced pluripotent stem cells from selected asthma discordant twins. This may advance asthma diagnostic procedures, improve molecular stratification of asthma affected subjects and create new avenues for therapy. We anticipate that genomic distribution of CNVs, combined with expression and targeted CpG methylation profiling in MZ twins, phenotypically discordant for asthma, will lead to identification of new asthma biomarkers. This will open up a field of investigation in twin research. We will provide a necessary proof-of-concept, leading the way to applications of the same principle using cohorts of twins discordant for other diseases.

Please contact Gunnar Sandberg NCP Health for more Information.