The ferritins are a family of proteins that function intracellularly to sequester iron that otherwise would be toxic to the cell. The molecules are comprised of 24 heavy and light subunits, the heavy:light ratio varying widely in a tissue-specific manner. We cloned DNA sequences for both the heavy (HL217-1) and light (HL227) subunits from a cDNA library derived from messages that are strongly regulated during in vitro-induced differentiation of a promyelocytic leukemia cell line, HL-60, into either neutrophils or macrophages. The heavy-subunit family (FTH) includes 15-20 genes and/or pseudogenes; the light-subunit family (FTL) includes at least three genes. We have confirmed and extended the chromosomal localization of the heavy-subunit "genes" to chromosomes 1-6, 8, 9, 11, 13, 14, 17, and X. We have also identified and characterized two genetic polymorphisms: FTH/BamHI and FTH/TaqI. FTH/BamHI localizes to chromosome 3, is biallelic, and has a heterozygosity frequency of .39, a minor allele frequency of .33, and a polymorphic information content (PIC) of .34. FTH/TaqI is measured by the presence or absence of a single 6-kb fragment that is absent (i.e., "homozygosity" being presumed) in approximately 63% of Caucasians (PIC = .27). We discuss the possibility that gene-family probes that hybridize to many discrete members of dispersed gene families could be used in conjunction with pulsed- or inverted-field gels to screen a large number of specific genomic regions for microdeletions.
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