Elsevier

Genomics

Volume 82, Issue 2, August 2003, Pages 238-244
Genomics

Regular article
Complex low-copy repeats associated with a common polymorphic inversion at human chromosome 8p23

https://doi.org/10.1016/S0888-7543(03)00108-3Get rights and content

Abstract

To characterize a submicroscopic, common 8p23 polymorphic inversion, we constructed a complete BAC/PAC-based physical map covering the entire 4.7-Mb inversion and its flanking regions. Two low-copy repeats (LCRs), REPD (∼1.3 Mb) and REPP (∼0.4 Mb), were identified at each of the inversion breakpoints. Comparison of the REPD and REPP sequences revealed that REPD showed high homology to REPP, with complex direct and inverted orientations. REPD and REPP contain six and five olfactory receptor gene-related sequences, respectively. LCRs at 8p23 showed multiple FISH signals from an Old World monkey to the human. Thus, multiplication of the LCR may have occurred at least 21–25 million years ago. We also investigated the frequency of the 4.7-Mb inversion in the general Japanese population and found that the allele frequency for the 8p23 inversion was estimated to be 27%.

Section snippets

A complete physical map

A complete BAC/PAC-based physical map covering the entire region from D8S1742 to D8S308 has been constructed (Fig. 1). The genetic distance between the two marker loci is about 18.7 cM, according to the Marshfield genetic map (http://research.marshfieldclinic.org/genetics). A total of 10 PACs, 62 BACs, and 11 virtual clones/sequences, including CTD-2009F9 (GenBank Accession No. AC084275), CTD-2151E19 (AC110024), CTD-3023L14 (AF289075), SCb-561b17 (AF238378), SCb-295J18 (AF252830), CTB-415D8

Discussion

We constructed a complete contig covering the common 8p23 polymorphic inversion and two LCRs, REPD and REPP, on each end. The size of the inversion, REPD, and REPP is 4.7 Mb, 1.3 Mb, and 400 kb, respectively. The orientation of REPD in comparison to REPP is a mixture of forward and inverted segments. Direct repeats can cause deletion or duplication, while inverted repeats can induce inversion [1], [2], [3]. In hemophilia A, 47% of severe cases are caused by inverted, small (9.5 kb) duplicons,

Physical map construction

The RPCI-1, RPCI-3, and RPCI-11 human BAC libraries were screened by PCR using STSs as described previously [23]. PCR-amplifiable DNA for the RPCI-11 library screening was purchased from Advanced GenoTechs Co. (Tsukuba, Japan). Contigs were constructed by means of STS content mapping using PCR. BAC DNA was extracted with Midi-Prep columns (Qiagen, Chatsworth, CA, USA). New STSs were generated from clone-end sequences using T7 and SP6 primers (see the legend to Fig. 1). Sequencing reactions were

Acknowledgements

We express gratitude to Ms. Kazumi Miyazaki, Naoko Takaki, Yasuko Noguchi, and Naoko Yanai for their technical assistance. N.M. was supported in part by a grant from the Inamori Foundation and N.N. by CREST from Japan Science and Technology Corporation.

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