Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0700208 (scoliosis)
 8,574 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In our previous study we showed that the inheritance of pronounced forms of idiopathic scoliosis was described by an autosomal-dominant major gene model assuming incomplete sex- and age-dependent penetrance. In the present study a search for the major gene was carried out by means of testing candidate genes. The aggrecan gene with known polymorphism of the number of tandem repeats in exon G3 was considered to be one of these candidate genes. Various alleles of this gene provide attachment of different number of chondroitin sulfate chains to a proteoglycan core protein, thereby changing functional properties of cartilage. Using the TDT analysis of 33 unrelated families consisting of a proband and his parents, we examined the existence of associations between the aggrecan alleles and the disease. Among nine alleles identified, three alleles with tandem repeats numbers of 25, 26, and 27 prevailed. We did not reveal preferable transmission of any of these alleles to the proband (TDT-statistics for different alleles varied from 0 to 0.71). There was also no correlation between the number of tandem repeats and the disease severity. Thus, either the polymorphism of the number of tandem repeats is not the direct reason for development of idiopathic scoliosis in the families tested, or its effect is too low to be detected using the samples examined.
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PMID:[Analysis of polymorphism of the number of tandem repeats in the aggrecan gene exon G3 in the families with idiopathic scoliosis]. 1189 16

The purpose of this work is the development of a family-based association test that allows for random genotyping errors and missing data and makes use of information on affected and unaffected pedigree members. We derive the conditional likelihood functions of the general nuclear family for the following scenarios: complete parental genotype data and no genotyping errors; only one genotyped parent and no genotyping errors; no parental genotype data and no genotyping errors; and no parental genotype data with genotyping errors. We find maximum likelihood estimates of the marker locus parameters, including the penetrances and population genotype frequencies under the null hypothesis that all penetrance values are equal and under the alternative hypothesis. We then compute the likelihood ratio test. We perform simulations to assess the adequacy of the central chi-square distribution approximation when the null hypothesis is true. We also perform simulations to compare the power of the TDT and this likelihood-based method. Finally, we apply our method to 23 SNPs genotyped in nuclear families from a recently published study of idiopathic scoliosis (IS). Our simulations suggest that this likelihood ratio test statistic follows a central chi-square distribution with 1 degree of freedom under the null hypothesis, even in the presence of missing data and genotyping errors. The power comparison shows that this likelihood ratio test is more powerful than the original TDT for the simulations considered. For the IS data, the marker rs7843033 shows the most significant evidence for our method (p = 0.0003), which is consistent with a previous report, which found rs7843033 to be the 2nd most significant TDTae p value among a set of 23 SNPs.
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PMID:A family-based likelihood ratio test for general pedigree structures that allows for genotyping error and missing data. 1838 89