UHX1 and PCTK1: precise characterisation and localisation within a gene-rich region in Xp11.23 and evaluation as candidate genes for retinal diseases mapped to Xp21.1–p11.2

Abstract

The gene for ubiquitin hydrolase on the X chromosome (UHX1), cloned and mapped to Xp21.2-p11.2, is a candidate gene for retinal diseases. We used fine mapping techniques to localise UHX1 between markers DXS1266 and DXS337, where congenital stationary night blindness (XlCSNB) and retinitis pigmentosa type 2 (RP2) are also located. Reevaluation of the UHX1 gene structure demonstrated five new exons, for a total of 21 exons and a predicted protein product of 963 amino acids. Evaluation of patients revealed no UHX1 mutations using SSCP (10 CSNB1 and 20 XLRP) or deletion screening with cDNA hybridisation (13 CSNB1 and 43 XLRP). Likewise, no aberrations were found in the nearby PCTAIRE1 (PCTK1) gene in 13 CSNB1 and 43 XLRP patients by deletion screening. Thus mutations of UHX1, and probably PCTK1, do not appear to cause common X-linked eye diseases. UHX1's role in patients with mental retardation may be appropriate for further investigations into UHX1 function.

Structural and functional characterization of the USP11 deubiquitinating enzyme, which interacts with the RanGTP-associated protein RanBPM

“…Therefore, we thought that the USP11 mRNA might be translated from an unknown ATG start codon located further upstream. Indeed, when Brandau et al [15] investigated the genetic structure of the USP11 gene on chromosome Xp11.2, the gene structure program XGRAIL2 predicted 21 exons and a 2889 bp open reading frame encoding 963 amino acids. To isolate a clone containing the additional upstream sequence, we screened another 4i10' independent clones of the Jurkat cell library, but we were unsuccessful in this regard.…”

“…Widespread tissue expression of UHX1 with 5-10-fold increased expression in the retina was shown [14]. Although UHX1 was proposed as a candidate gene for retinal disease in light of these findings, recent examination of 43 patients with X-linked retinal disease revealed no mutations in the UHX1 sequence [15]. Because the family of UBP is large and complex, a systematic nomenclature for human UBPs was proposed [16].…”

Polymorphic X-Chromosome Inactivation of the Human TIMP1 Gene

“…To determine if the expression from the inactive X chromosome extended beyond TIMP1, we analyzed the expression of genes surrounding TIMP1, within the gene-rich region of Xp11.23 ( fig. 1A) (Coleman et al 1994;Knight et al 1994;Derry et al 1995;Brandau et al 1998). RT-PCR was performed with primers for TIMP1, ARAF-1 (a rafrelated gene located 20 kb distal to TIMP1), ELK1 (a transcription factor and proto-oncogene 50 kb proximal to TIMP1), and two zinc-finger genes (ZNF41 and ZNF157), which are located !100 kb from TIMP1.…”

“…A, Schematic map of genes flanking TIMP1. ZNF41 is present in a YAC spanning the region represented by the arrow; however, the unbroken portion of the arrow represents the most likely area for ZNF41, since an overlapping YAC that was negative for ZNF41 was shown to be deleted in this region (Brandau et al 1998). B, Products from amplification of cDNA derived from the hybrids, listed with human-specific primers for the genes shown.…”

“…These regions of the inactive X chromosome behave more like the active chromosome, replicating earlier and retaining more acetylation of histones than does the remainder of the inactive X chromosome (Schempp and Meer 1983;Jeppesen and Turner 1993). Human TIMP1 is in a generich region containing ARAF1, ELK1, ZNF41, and ZNF157 within 100 kb (Coleman et al 1994;Knight et al 1994;Derry et al 1995;Brandau et al 1998). We therefore assessed whether this entire region was expressed from the inactive X chromosome, by examining the expression of these genes flanking TIMP1.…”