Date of Award

1998

Document Type

Thesis

Publisher

Edith Cowan University

Degree Name

Master of Science

Faculty

Faculty of Communications, Health and Science

First Supervisor

Dr Luba Kalaydjieva

Abstract

The aim of this research was to perform exclusion on a rare form of hereditary autosomal dominant polycystic kidney disease (ADPKD). To-date, two genes for ADPKD have been identified: PKDI which has been localized to the short arm of chromosome 16 and PKD2 which has been localized to the long arm of chromosome 4. However, a small number of families have been reported that have not shown linkage to either of these two loci, thus suggesting the existence of at least one additional locus (PKD3). Two families that are affected with ADPKD and do not show linkage to PKDI or PKD2 have participated in this study. Both families are of Bulgarian origin and between them contain 9 affected individuals. Even though these families are small, they are large enough to exclude a large proportion of the genome as the location of the PKD3 gene. The availability of these families and the discovery of other non PKD1/PKD2 families has provided a rare opportunity to perform exclusion mapping of the PKD3 gene which will eventually lead to mapping and cloning of this gene. A systematic search of the human genome was performed using polymorphic markers (from the Research Genetics screening set version 4a) which span the human genome at an average distance of 16cM. The results were then analysed statistically using the computer programs EXCLUDE, LINKAGE and GENEHUNTER. From this study the highest Lod score obtained was a multipoint Lod score of 2.95 on 22q 11.21 at marker D22S446. Two other regions also produced relatively high Lod scores, the first being on 4q22.1 at marker D4S1647 which produced a Lod score of 1.42 and the second region being on 11p15.2 at marker D11S902 which produced a Lod score of 1.41. These results provide a strong indication as to the location of the PKD3 gene however, before linkage can be claimed with any degree of certainty the sample size must be increased with the addition of other non PKD1/PKD2 families. This increases the possibility of obtaining a Lod score of 3.00 or greater and thus proving linkage to the PKD3 gene.

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