title: A study of genetic linkage heterogeneity in 35 adult-onset polycystic kidney disease families.
abstract: A genetic heterogeneity analysis of 35 kindreds with adult-onset polycystic kidney disease (ADPKD) was carried out using the D16S85, D16S84, D16S125 and D16S94 loci that are closely linked to the PKD1 locus on chromosome 16. The results show that the likelihood of two ADPKD loci is 2,514.9 times greater than for a single locus (P < 0.0001). The maximum likelihood lod score is 27.38 under heterogeneity with PKD1 lying 4.9 cM proximal to D16S85 (in males). At least 3% of kindreds are unlinked to PKD1, since the 95% confidence limits of alpha, the proportion of families linked to PKD1, are 0.54-0.97. Only 2 out of 35 kindreds (5.7%) show statistically significant evidence of non-linkage to PKD1, with conditional probabilities of 0.987 and 0.993 that the disease locus is unlinked. This confirms the existence of a small subgroup of ADPKD kindreds that are unlinked to PKD1 and provides a firm basis for genetic counselling of this population on the basis of DNA probes.
authors.affiliation: MRC Human Genetics Unit, Western General Hospital, Edinburgh, UK.
authors.forename: A F
authors.initials: AF
authors.lastname: Wright
authors.forename: P W
authors.initials: PW
authors.lastname: Teague
authors.forename: S E
authors.initials: SE
authors.lastname: Pound
authors.forename: P M
authors.initials: PM
authors.lastname: Pignatelli
authors.forename: A M
authors.initials: AM
authors.lastname: Macnicol
authors.forename: A D
authors.initials: AD
authors.lastname: Carothers
authors.forename: R J
authors.initials: RJ
authors.lastname: De Mey
authors.forename: P L
authors.initials: PL
authors.lastname: Allan
authors.forename: M L
authors.initials: ML
authors.lastname: Watson
mesh_terms: D000328:Adult; D016009:Chi-Square Distribution; D002885:Chromosomes, Human, Pair 16; D005260:Female; D008040:Genetic Linkage; D005820:Genetic Testing; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D016013:Likelihood Functions; D008297:Male; D016891:Polycystic Kidney, Autosomal Dominant / Q000175:diagnosis / Q000235:genetics*