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UBC Theses and Dissertations

Isolation and mapping of clones from human chromosome 5 Bernard, Lynn Elizabeth


This thesis describes the isolation and mapping of DNA clones from human chromosome 5, with emphasis on the 5q11.2-q13.3 region. This region is of interest because of a Vancouver family in which trisomy for the 5q11.2-q13.3 region co segregates with schizophrenia and renal anomalies. The 5q11.2-q13.3 region is of additional interest since chronic spinal muscular atrophy has been linked to markers within this region. A novel technique, Alu PCR differential hybridization, was developed to isolate clones from the 5q11.2-q13.3 region. The somatic cell hybrid HHW1O64 contains a chromosome 5 with an interstitial deletion of 5q11.2-q13.3, derived from a carrier member of the family segregating for the segmental trisomy. Alu PCR differential hybridization was used to isolate twenty chromosome 5 clones absent from the HHW1O64 hybrid. Radiation hybrid mapping was used to determine a rough order of clones isolated by Alu PCR differential hybridization. Order information was used to select clones to screen for polymorphisms. Nine polymorphic systems were detected. Multipoint linkage mapping of two of the new polymorphisms (D5S257 and D5S268) placed them onto the p arm of chromosome 5. This result was unexpected, since D5S257 and D5S268 were isolated based on their absence from the HHW1O64 hybrid. The HHW1O64 somatic cell hybrid therefore contains a deletion within the p arm of chromosome 5 in addition to the expected interstitial deletion of 5q11.2- q13.3. Analysis of D5S257 and D5S268 in the family segregating for the segmental trisomy indicated that the rearrangement in this family does not involve Sp. Multipoint linkage analysis of the polymorphism associated with D5S260 placed this marker between two chromosome 5 index markers (D5S76 and D5S21) which had been mapped outside the 5q11.2-q13.3 interstitial deletion in HHW1O64. This map position was unexpected, since D5S260 was isolated on the basis of absence from the HHW1O64 hybrid. The most likely explanation for the inconsistency between the linkage and somatic cell hybrid data is that the chromosome 5 present in the HHW1O64 hybrid is deleted for DNA both proximal and distal to D5S76. This complex 5q rearrangement is present in the family segregating for the segmental trisomy, based on the analysis of D5S260 and D5S76 in this family.

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