Detailed genetic mapping around a putative prostate-specific membrane antigen locus on human chromosome 11p11.2

Abstract

Physical mapping of the human prostate-specific membrane antigen gene (FOLH) has not been straightforward. Previously, localisations of this gene to either 11p11.2 or 11q14 have been described. This raised the possibility of the presence of more than one related FOLH gene in man. We now present detailed characterisation of the region around a FOLH gene in a 500-kb non-chimaeric YAC clone, putatively assigned to 11p11.2. This clone contains two known microsatellites, D11S1326 and D11S1357 which have been previously mapped unequivocally to the 11p11.2 region at 62.5 cM. This data strongly supports the original 11p11.2 localisation of FOLH. The YAC clone also has a putative EST at each of its ends and these have thus been physically positioned on this chromosome. However, the two regions previously highlighted at 11p11.2 and 11q14 are apparently extensively duplicated, as evidenced by the appearance of dual FISH signals with a number of different genomic probes selected across this 500-kb 11p11.2 region.

Identification of a Novel Microsatellite Marker Tightly Linked to the KAI–1 Gene for Predicting Prostate Cancer Progression

“…More recently, this 11p localisation has been confirmed [10]. Further investigations have also revealed that these interesting PSM loci on 11p11.2 and 11q14 are duplicated over a region of at least 500 kb [9]. …”

“…This was in contrast to the findings by Rinker–Schaeffer et al [8]who only detected a single 11q14 PSM fluorescent in situ hybridisation (FISH) signal at high stringency and therefore suggested the long arm as being the true location of the known PSM gene. On balance, the 11p11.2 region is now thought to be the more likely location of the known human PSM gene as evidenced by sequencing and detailed genetic mapping studies [9]. More recently, this 11p localisation has been confirmed [10].…”

Prostate-specific membrane antigen (FOLH1): recent advances in characterising this putative prostate cancer gene

“…25 These studies also suggest extensive genetic duplication in these two regions (11p11.2 and 11q14). This phenomenon is observed elsewhere in the human genome and usually some members of the resulting gene families eventually lose function and become pseudogenes.…”

“…However, this has now been resolved. 25,52 Detailed genetic analysis has allowed localisation of the FOLH1 gene to the 1lp11.2 chromosomal region at 62.5 cM, with a related FOLH2 gene at 11q14. Interestingly there appears to be extensive genetic duplication, over at least 500 kb, in these two regions.…”

“…Interestingly there appears to be extensive genetic duplication, over at least 500 kb, in these two regions. 25 Complete analysis of the molecular genetics of the FOLH1 gene(s) is essential to facilitate ongoing clinical evaluations. The utilisation of 111 In labelled anti-PSM/FOLH1 antibody to assess the extent of disease has shown very promising initial results when compared to other prostate cancer`speci®c' antibodies.…”