Duplications on human chromosome 22 reveal a novel ret finger protein-likegene family with sense and endogenous antisense transcripts

Analysis of 600 kb of sequence encompassing the beta-prime adaptin (BAM22) gene on human chromosome 22 revealed intrachromosomal duplications within 2 2q12-13 resulting in three active RFPL genes, two RFPL pseudogenes, and two pseudogenes of BAM22. The genomic sequence of BAM22 psi 1 shows a remarkab le similarity to that of BAM22. The cDNA sequence comparison of RFPL1, RFPL 2, and RFPL3 showed 95%-96% identity between the genes, which were most sim ilar to the Ret Finger Protein gene from human chromosome 6. The sense RFPL transcripts encode proteins with the tripartite structure, composed of RIN G finger, coiled-coil, and B30-2 domains, which are characteristic of the R ING-B30 family. Each of these domains are thought to mediate protein-protei n interactions by promoting homo- or heterodimerization. The MID1 gene on X p22 is also a member of the RINC-B30 Family and is mutated in Opitz syndrom e (OS). The autosomal dominant form of OS shows linkage to 22q11-q12. We de tected a polymorphic protein-truncating allele of RFPL1 in 8% of the popula tion, which was not associated with the OS phenotype. We identified 6-kb an d 1.2-kb noncoding antisense mRNAs of RFPLIS and RFPL3S antisense genes, re spectively. The RFPLIS and RFPL3S genes cover substantial portions of their sense counterparts, which suggests that the function of RFPLIS and RFPL3S is a post-transcriptional regulation of the sense RFPL genes. We illustrate the role of intrachromosomal duplications in the generation of RFPL genes, which were created by a series of duplications and share an ancestor with the RING-B30 domain containing genes from the major histocompatibility comp lex region on human chromosome 6.