title: The usefulness of three biallelic restriction fragment length polymorphisms versus a polymorphic dinucleotide tandem repeat polymorphism at the low-density-lipoprotein receptor gene locus for diagnosis of familial hypercholesterolemia.
abstract: Indirect molecular diagnosis of familial hypercholesterolemia is possible based on genetic linkage analysis of DNA polymorphisms at the low-density-lipoprotein receptor gene locus in family studies. The use of biallelic restriction fragment length polymorphisms, however, is restricted by their low degree of heterogeneity, and therefore several of these markers have to be combined. To overcome these restrictions we examined the value and applicability of an (AT)n tandem repeat polymorphism at the 3' untranslated region of the gene, alone and in combination with three biallelic restriction fragment length polymorphisms in 35 independent healthy subjects and in familial hypercholesterolemia families with 23 parents and 52 children. For each family one of the parents had the clinical diagnosis of familial hypercholesterolemia. The probands were genotyped using the TaqI, HincII and NcoI restriction fragment length polymorphism and the (AT)n tandem repeat polymorphism of the gene. The heterozygosity index (0.60) and the polymorphism information content (PIC value) (0.53) of the ATn repeat polymorphism were higher compared to each single biallelic restriction fragment length polymorphism (heterozygosity index 0.26-0.54; PIC value 0.24-0.36). The combined PIC value of all three biallelic restriction fragment length polymorphisms (0.79) was comparable to the combination of the HincII and the ATn polymorphism (0.74). Using these two markers, a definitive molecular diagnosis could be made in 36 children from 15 parents compared to just 12 parents and their children using the three biallelic restriction fragment length polymorphisms. We conclude that the ATn tandem repeat polymorphisms is useful for indirect molecular diagnosis of familial hypercholesterolemia in affected families.
authors.affiliation: Medizinische Poliklinik, Klinikum Innenstadt, Ludwig-Maximilians-Universität München, FRG.
authors.forename: N
authors.initials: N
authors.lastname: Weiss
authors.forename: V
authors.initials: V
authors.lastname: Gudnasson
authors.forename: P
authors.initials: P
authors.lastname: Ostwald
authors.forename: S
authors.initials: S
authors.lastname: Humphries
authors.forename: H
authors.initials: H
authors.lastname: Schuster
authors.forename: C
authors.initials: C
authors.lastname: Keller
mesh_terms: D002874:Chromosome Mapping; D005260:Female; D008040:Genetic Linkage; D005819:Genetic Markers; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000175:diagnosis*; D008297:Male; D012150:Polymorphism, Restriction Fragment Length; D011973:Receptors, LDL / Q000235:genetics*; D012091:Repetitive Sequences, Nucleic Acid
chemical_list: D005819:Genetic Markers; D011973:Receptors, LDL