Genetic analysis of plasma XXXX , apoprotein B, and lipoproteins in a large Amish pedigree with @entity25589 .

@entity1 @entity34893 @entity9542 @entity1423 @entity25589 @entity4741 @entity453 @entity5068 @entity165
We previously reported the finding of @entity25589 , @entity4741 , and hyperapobetalipoproteinemia (hyperapoB) in five siblings in a large Amish pedigree ascertained through a 13-year-old @entity1 who died suddenly from advanced @entity453 . Here, we present further analyses of the plasma levels of the plant @entity5068 , @entity9542 , of low density (beta) lipoprotein (LDL) @entity5068 , and of @entity34893 protein. Of 254 relatives and spouses of the proband, 90.5% were examined. A series of genetic models were explored using a pedigree analysis where parameters reflecting frequency, transmission, and penetrance of putative genotypes were examined simultaneously using a maximum likelihood approach. Segregation analysis of the @entity9542 levels showed that the phenotype of @entity25589 was controlled by a rare autosomal recessive gene. There was also significant familial correlation in plasma @entity9542 levels that was attributed to a polygenic component under a mixed model but could also be due to shared environments such as diets. The recessive model was supported by our finding that the plasma @entity9542 levels in the parents and in six @entity1 born to three of the five sitosterolemics were less than 1 mg/dl, well within the normal range. The phenotype of hyperapoB is based on an elevated level of @entity34893 protein in the presence of a normal LDL @entity165 level (low LDL @entity5068 to @entity34893 ratio). For both LDL @entity5068 and @entity34893 , a polygenic model showed a slightly greater improvement in ln likelihood than did the Mendelian single locus model when both were compared to a sporadic model. Similar results were obtained for @entity5068 levels of high density (alpha) lipoprotein (HDL) @entity5068 . When segregation analysis was performed using the ratio of LDL @entity5068 to @entity34893 , the Mendelian single locus model gave a slightly better fit to the data than did the polygenic model. While the analyses presented here provided unequivocal evidence for the recessive phenotype of @entity25589 , we also identified a possible single gene factor that could account for the major portion of the strong @entity1423 in the ratio of LDL @entity5068 to @entity34893 , and to a lesser extent @entity34893 . However, there is clear evidence of @entity1423 for these traits in this pedigree beyond that due to Mendelian components.
