Gene assignments

A total of 36 new and refined assignments to chromosome 1q were reported since the previous chromosome 1 workshop (Table 5). Most of the assignments were determined by FISH while a few were determined by RH mapping. In addition, more loci (genes, ESTs, STSs) were localized on contigs of YAC and bacterial clones in 1q (Table 6). Of note are SLC19A2 and EBAF, two new genes associated with human disorders. The SLC19A2 gene was identified through the successful positional cloning of the gene causing thiamine responsive megaloblastic anaemia syndrome at 1q23.2-q23.3 (Diaz et al., 1999a; Labay et al., 1999). EBAF and its paralog, LEFTB, were identified through a screen of human homologs for the mouse Lefty1 gene (Kosaki et al., 1999). The two human homologs map to 1q42 and are separated by 50 kb. A mutation in EBAF was identified in two cases of left-right axis malformations.

Physical mapping

Eleven new contig maps were reported for chromosome 1q since the previous chromosome 1 workshop, with six of these presented at the current workshop (Table 6). The physical maps include contigs of YAC clones and bacterial clones. In last year's list, 5/12 contigs contained bacterial clones, while in this year's list, 9/11 contain bacterial clones, demonstrating the growing trend toward sequence-ready bacterial clone (SRBC) contigs. The two largest SRBC contigs are located at 1q25.2 (Carpten et al., this report) and 1q21 (South et al., 1999). These gene-rich regions continue to be the focus of sequencing efforts on chromosome 1q.

Gene structures

The genomic structure for nine genes from 1q were reported since the last workshop (Table 7). The S100A7 gene is a member of the S100 family of genes that encode for small calcium-binding proteins with two EF-hands and it maps within the 1q21 epidermal differentiation complex. Although the S100A7 gene is markedly overexpressed in the skin lesions of psoriatic patients, Semprini and colleagues (Semprini et al., 1999) excluded it as a candidate for familial psoriasis susceptibility because they did not identify any mutations in a cohort of 15 unrelated individuals with familial psoriasis linked to chromosome 1q. The genomic structure for the SLC19A2 gene was obtained from the complete genomic sequence generated by the Sanger Centre. This information led to the rapid identification of mutations in individuals with TRMA (Diaz et al., 1999a; Labay et al., 1999). Following the genomic structure determination of the 1q21 geneTNNT2, a rapid assay for screening mutations in individuals with familial hypertrophic cardiomyopathy (FHC) was developed, and one new mutation was identified. In addition, three polymorphic short tandem repeats identified within the gene will be useful for mapping FHC pedigrees to the CMH2 locus at 1q32 (Gerull et al., 1998).