Description |
A theoretical study, aimed at the quantification of the discriminating power of various pedigree structures, provided evidence that : (1) large sibships are the single most informative pedigree feature. (2) the complete phenotypes of parents should be gathered before deciding whether to test the offspring, and (3) a collection of individuals in a single pedigree is more informative than two pedigrees each of half the size of the original. Likelihood analysis of a large Mormon pedigree, using transferring saturation as the quantitative phenotypic trait, indicated that the inheritance of hemochromatosis was recessive, with partial expression in heterozgotes. The lod score of 6.88 (? = 0) was strongly indicative of linkage between the hemochromatosis (h) locus and the Major Histocompatibility System (HLA) loci. Data from seven other pedigrees was shown to be compatible with a recessive mode of inheritance and tight linkage to HLA. The sum of the lod scores from these seven additional pedigrees was 2.69 (? = 0). The set of individual from all of the pedigrees studies were assigned to one of three genotypic groups - hh, Hh, or HH - on the basis of HLA haplotype, assuming tight linkage. A stepwise linear discriminant function was used (1) to obtain a multivariate measure of iron status which would differentiate the genotypic groups better than transferring saturation alone, and (2) to compare the information content of six measures of iron status: serum iron, transferring saturation, serum ferritin, urinary iron excretion after the administration of deferoxamine, stainable iron in hepatic parenchymal cells, and hepatic iron concentration. Results indicated that transferring saturation value can generally distinguish abnormal homozygotes (hh) from the other two genotypic groups. There was considerable overlap between the heterozygotes and the normal homozygotes, and not of the six measures . |