Determining the risk of scoliosis comprising determining cellular response to mechanostimulation
AssigneeChu Sainte-Justine
InventorsAlain Moreau, Niaz Oliazadeh, Kristen Fay Gorman, Robert Eveleigh, Guillaume Bourque
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Abstract
Disclosed herein are novel molecular markers associated with idiopathic scoliosis (IS). Accordingly, the present invention concerns novel methods of identifying subjects at risk of developing IS or suffering from IS and of genotyping and classifying IS subjects into genetic and functional groups. Also provided are compositions, DNA chips and kits for applying the methods.
Claims36
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A method of determining the risk of or predisposition to developing a scoliosis in a subject comprising:
- (a) (i) determining the average length of cilia on the surface of cells in a cell sample from the subject;
- (ii) determining the number of cells with elongated cilia in a cell sample from the subject
- (iii) determining the number of ciliated cells in a cell sample from the subject;
- or
- (iv) any combination of one of (i), (ii) and (iii),
- wherein an increase in the average length of cilia, an increase in the number of cells having elongated cilia or a decrease in the number of ciliated cells in the cell sample from the subject as compared to that in a control sample is indicative of an increased risk of or predisposition to developing a scoliosis;
- (b) determining a cellular response to mechanostimulation of cells in a cell sample from a subject, wherein the determining comprises:
- (i) applying mechanostimulation to cells in a cell sample from the subject;
- and
- (ii) measuring the expression level of at least one mechanoresponsive gene, wherein the at least one mechanoresponsive gene is ITGB1;
- ITGB3, CTNNB1;
- POC5, BMP2, COX-2, RUNX2, CTNNB1 or any combination thereof;
- (iii) comparing the expression level measured in (b)(ii) to that of a control sample, wherein an altered expression level in said mechanoresponsive gene as compared to that of the control sample is indicative of an increased risk of or predisposition to developing a scoliosis;
- or
- (c) a combination of (a) and (b).
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A method of (A) determining the risk of developing a scoliosis in a subject;
- or (B) genotyping a subject suffering from Idiopathic scoliosis or at risk of developing a scoliosis, the method comprising detecting in a cell sample from the subject, the presence or absence of a polymorphic marker in at least one allele of at least one gene listed in Table 4 or substitute marker in linkage disequilibrium with the polymorphic marker.
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A composition or kit or DNA chip comprising at least one oligonucleotide probe or primer for the specific detection of a polymorphic marker in a gene listed in Table 4.
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A composition comprising (i) a cell sample from the subject;
- and (ii) one or more reagent for detecting (a) the length of cilia at the surface of cells;
- (b) the number of cells with elongated cilia;
- (c) the number of ciliated cells;
- (d) the level of expression of at least one mechanoresponsive gene;
- and/or (e) the presence or absence of a polymorphic marker in at least one gene listed in Table 4 or a substitute marker in linkage disequilibrium therewith.
An oligonucleotide primer or probe for detecting the presence or absence of a reference allele or risk variant allele defined in Table 6, preferably further comprising a label.
Dependencies are inferred from the claim text.