New models of inheritance of complex characters and their use in segregation analysis of idiopathic scoliosis

New methods of segregation analysis of alternative traits have been develop ed. These methods make it possible to take into account the sex and age spe cificity of disease manifestation. Hence, they extend the range of genetic hypotheses to be tested and ensure the correct analysis of inheritance of c omplex pathologies in humans. Segregation analysis of idiopathic scoliosis performed in this study demonstrates the possibilities of the new methods. Based on pedigrees of 93 probands, it has been demonstrated for the first t ime that the inheritance of severe (degrees II to IV) forms of this disease can be described by a model that assumes a dominant major gene with incomp lete, sex- and age-dependent penetrances of all genotypes. According to thi s model, severe forms of idiopathic scoliosis do not develop if the mutant allele is absent (the penetrance of genotype A(1)A(1) is zero). The probabi lities of the disease for subjects with genotypes A(1)A(2) and A(2)A(2) are similar and approximately equal to 0.3 and 0.5 for males and females, resp ectively. Mild (degree I) forms of idiopathic scoliosis are heterogeneous. A progressive disease may be expected only in the patients that carry the m utant allele.