mango
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http://me-forskning.no/oppdatering-fra-haukeland-om-prosjektet-pa-genetisk-predisposisjon/
Translated by Google:
Translated by Google:
Update from Haukeland about the project on genetic predisposition.
The following is an update from Haukeland University about the project on genetic predisposition to ME / CFS.
Brief status of the project on genetic predisposition to ME / CFS
In a published study shows a clear genetic predisposition to ME (Albright et al, 2011). This was a population-based study in which risk of ME was 2.7 times higher in first-degree relatives of CFS patients, 2.3 times higher in second degree relatives, and 1.93 times higher in cubic relatives, compared with the risk of ME in the general population.
Our research group at the Department of Oncology, Haukeland University Hospital, has in recent years been contacted by several independent families with striking accumulation of ME that everyone has wanted us to do further analyzes on mapping of genetic predisposition. We believe mapping of gene changes in affected patients will be an important step forward in the understanding of disease mechanisms.
We conducted eksom sequencing from both CFS patients and healthy family members, where all the coding regions of the genome, including the flanking regions intro characterized. This technique is considered experimental diagnostic / research and is not considered a full investigation of all genetic variants that exist in a human. Initially we will only answer the question of what is the molecular genetic predisposition to ME disease in our patients. Eksomet constituting the coding parts of genes including the flanking intron portions, is approximately 1.5% of the total DNA of a human cell, but about 85% of all known mutations is still located therein.
We imagine that some families may have genetic variants of immune genes such as HLA genes, where it is known that specific HLA types are correlated with various autoimmune diseases. HLA genes in ME examined in a specific project at OUS, led by Benedicte Lie, Marthe Viken and Torstein Egeland.
At Haukeland Hospital, we are most concerned about families with significant accumulation of ME disease, often with multiple siblings with onset relatively early age, often with a relatively severe illness, and preferably with ME disease in successive generations. We believe any such families may have genetic variants directly in "effector" of symptoms (which symptoms are created), and where the detection of such variants can tell us about disease mechanisms.
We have completed finished eksom sequencing from a total of 18 people, from two different families with significant incidence of ME disease among first and second degree relatives. We have started with analyzes from a third family.
For the two families which we have carried eksom sequencing and subsequent analysis, we have more relevant gene variants being investigated further.
Currently we have focused on an interesting genetic variation (mutation) that all the sickness of a family has, and which occurs in approximately 2/1000 of a European general population. The variant also occurs in a few of the patients included in the clinical trials our. We focus efforts towards this variation now and have taken skin biopsy (all cells in the affected've the same gene variant) for cultivating cell cultures and examine energy turnover closer.
We have created cells in which mutation is "inserted" by means of gene transfection, and where we can "turn up" the expression of the mutated variant significantly, and see the implications of cells.
We believe the version we're dealing with now may be relevant to the disease, and data so far fits in well with the work we otherwise perform now, to identify disease mechanisms of ME closer.
04/15/16
Øystein Fluge Olav Mella Ove Bruland