Human chemokines fractalkine (SCYD1), MDC (SCYA22) and TARC (SCYA17) are clustered on chromosome 16q13 1

Chemokines are a large family of small secreted proteins that regulate migration of white blood cells. Based on the arrangement of the first two of the four conserved cysteine residues, chemokines are classified into four subfamilies, CXC, CC, C and recently identified CX3C. Most of the human genes for the CC chemokines are clustered at chromosome 17q11.2 (Naruse et al., 1996). Previously we identified a novel CC chemokine TARC (thymus and activation-regulated chemokine) (Imai et al., 1996) and localized its gene (SCYA17) at chromosome 16q13 (Nomiyama et al., 1996). Recently, Bazan et al. (1997) and Pan et al. (1997) mapped the CX3C chemokine fractalkine/neurotactin gene (SCYD1) to chromosome 16. More recently, Godiska et al. (1997) reported isolation of a cDNA encoding a novel CC chemokine MDC (macrophage derived chemokine) and mapped its gene (SCYA22) to the same chromosome. It is therefore important to determine the exact relationship of these three chemokine genes on chromosome 16.The DNAs of somatic cell hybrids containing various portions of human chromosome 16 (Callen et al., 1990; Whitmore et al., 1993) were amplified with fractalkine and MDC primers.Amplicons:140 bp (fractalkine) and 199 bp (MDC)PCR conditions:35 cycles of 95°C 30 s, 60°C 30 s, 72°C 1 minBAC clones were identified by screening the human BAC library (Research Genetics, Huntsville AL) by PCR with the above fractalkine primers.Chromosome locations of the fractalkine and MDC genes were examined by analyzing somatic cell hybrids containing various portions of human chromosome 16 with PCR. The results showed that the fractalkine and MDC genes were both mapped between the chromosome breakpoints CY18A(P1) and CY126, the same region where the TARC gene had been previously localized (Nomiyama et al., 1996) (Fig. 1). To further determine whether these genes are closely adjacent to each other, the California Institute of Technology BAC library of average 130-kb insert size (Kim et al., 1996) was searched for clones containing the fractalkine gene by PCR. Three clones, 15i17, 50f12 and 185f16, were identified. When these BAC clones were analyzed by PCR, 15i17 and 185f16 were found to contain both the TARC and MDC genes, whereas 50f12 was found to contain only the MDC gene (Fig. 1). These results show that the three genes are located within a short segment, probably 200 kb or less. This supports their close evolutionary relationship.Locations: SCYD1 16q13; SCYA22 16q13Hybrid cell panel: Callen et al. (1990) and Whitmore et al. (1993)Supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Science, Sports and Culture of Japan.