Chromosome 1q21: Integrated analysis of expression and chromosomal organisation of genes localised on human chromosome 1q21 - implications for human disease and cancer

• Research unit: EU RFP
• Project number: 95.0215-2

Key words (English)

Human chromosome 1q21; epidermis; gene mapping; gene regulation; genetic diseases

Alternative project number (English)

EU project number: BMH4CT950319

Research programs (English)

EU-programme: 4. Frame Research Programme - 4.2 Agriculture and agroindustry

Short description (English)

See abstract

Further information (English)

Full name of research-institution/enterprise:
Université de Lausanne
Service de Dermatologie et Vénéréologie
CHUV BT-437

Partners and International Organizations (English)

1q21 Consortium; Coordinator:
Universitätsklinikum Rudolf Virchow (D)

Abstract (English)

The sequence analysis of the repetin gene on cosmid I 05H4 has been finished. A total 6kbp has been sequenced which includes the complete gene and 1kbp of the upstream promoter sequence. The second cosmid 31 H23 has been partially sequenced and no major differences have been found so far. Two partial cDNA clones have been isolated. The first one is spanning the 3 ' end of the cDNA (1400 nt) and was isolated by screening a keratinocyte cDNA library constructed in ~ZAP. A second one contains the 5 £ end of the cDNA (2300 nt) and was isolated by RT/PCR technology from RNA isolated from suspension cultures of keratinocytes. Primers were designed based on the sequence of the cDNA clone described above and the putative translation start site deduced by sequence homology analysis with the mouse gene. The overlap between the two clones is 160 nucleotides. Sequence analysis of the cDNA has been completed and demonstrated an open reading frame of 785 amino acids. The protein contains 28 highly conserved repeats of 12 amino acids and a putative calcium binding domain in the N-terminal region. Calcium overlay assays using bacterially expressed protein showed clearly that the NH2-terminal domain binds reversibly calcium. Immunofluorescence analysis using an affinity-purified peptide antibody directed against the repetitive region indicated that repetin is expressed in the upper granular layer of human epidermis, foreskin and tongue. Immuno-electron microscopy provided evidence that repetin is expressed in organelles which resemble keratohyalin granules. Northernblot analysis revealed that repetin is expressed at moderate levels when keratinocytes are cultured in suspension with 1.75 % methylcellulose. In submerged culture only very low levels of repetin mRNA are expressed. These results indicate that repetin is a marker for late epidermal differentiation.

The following people of 1q21 consortium are acknowledged for their contribution towards this work: Dietmar Mischke, Ingo Marenholz, Claude Backendorf, David Fischer, Dean Nizetic, Andrew South, Anne Forus

References in databases (English)

Swiss Database: Euro-DB of the
State Secretariat for Education and Research
Hallwylstrasse 4
CH-3003 Berne, Switzerland
Tel. [phone]
Swiss Project-Number: 95.0215-2