Gene assignments

In total, 19 genes were newly assigned to chromosome 1q or were refined in their localization since the previous workshop (Table 4). The main mapping tools for chromosome assignments were fluorescent in situ hybridization (FISH) and radiation hybrid mapping. Three new genes, COAS1, COAS2 and COAS3, were mapped to 1q21 by direct selection from a YAC clone that was previously localized to this region by FISH (Forus and coworkers, this workshop). This YAC clone is a marker for a region that is often amplified in human malignancies; hence the name Chromosome One Amplified Sequences (COAS). The gene encoding the calcium-activated potassium channel 3 (KCNN3) was localized to the region of 1q21 containing a locus for a familial form of schizophrenia. However, mutation analysis failed to identify any etiologic mutations (Stober et al., 2000). Many additional genes were assigned through physical mapping efforts near the HLA paralogous region at 1q22-q23, the MYOC (myocilin) gene at 1q24, the HPC1 (Hereditary Prostate Cancer) region at 1q24-q31, the RCA (Regulation of Complement Activation) gene cluster at 1q32 and the VWS (Van der Woude syndrome) locus at 1q32-q41 (Table 5).

Physical mapping

Since the previous chromosome 1 workshop nine new or updated physical maps were reported, including five that were presented at this workshop (Table 5). Two groups presented transcript maps from BAC/PAC contigs that were presented at last year's workshop. Carpten and collaborators identified 60 transcripts from a 6 Mb region at 1q24-q31 and are searching for mutations that cause susceptibility to prostate cancer. Bjork and coworkers identified 38 transcripts from a 1.1 Mb contig from 1q32-q41 and continue to look for mutations that cause the clefting disorder Van der Woude syndrome. Three presentations described new physical maps. Shiina and colleagues described a 3.7 Mb contig from 1q22-q23 that is paralogous to the HLA region at 6p21.3. This region contains genes of immunological importance and a cluster of olfactory receptor genes. Ewens and coworkers created a 7-10 Mb sequence-ready contig at 1q42-q43 that spans a susceptibility locus for insulin-dependent diabetes. Hoffman and collaborators constructed a 1.5 &endash; 2.0 Mb contig at 1q44 that covers the locus for familial cold urticaria; two known genes and 27 ESTs were subsequently identified from this region.

A search of the literature identified four additional new physical maps within 1q. A search for clones derived from the pericentromeric regions of all human chromosomes included a BAC clone from 1q12 (Horvath et al., 2000). Vollrath and Jaramillo-Babb (Vollrath and Jaramillo-Babb, 1999) constructed a 2 Mb contig at 1q24 that contains two disease genes, myocilin (MYOC) and flavin-containing monooxygenase (FMO3). Finally, two groups mapped the RCA (Regulator of Complement Activation) gene cluster to 1q32. Rodriguez de Cordoba and coworkers (Rodriguez de Cordoba et al., 1999) constructed an ordered transcript map spanning a 21 cM region by integrating linkage mapping data with radiation hybrid mapping data. The map included 61 transcripts including 15 that are complement-related genes. These 15 genes are divided into two gene groups (CEN-HF1, FHR1, FHR4/FHR3, FHR2, F13B; and C4BPB, C4BPA, SRP72, DAF, CR2, CR1, MCP-TEL) that are separated by a 14 cM region that contains unrelated genes. Vollmer and collaborators (Vollmer et al., 2000) constructed a YAC/PAC contig spanning the second gene group described in the previous study. When the two maps were compared, the gene content was very similar and the order of the genes placed on both maps was identical. This region contains the locus for glomerulopathy with fibronectin deposits (GFND). The CR2, MCP and DAF genes were screened for mutations, but none were found (Vollmer et al., 2000).