Neuropathy (for review, see Lupski and Garcia 2001). CMT1A is the most common inherited peripheral neuropathy and accounts for 70% of CMT type 1 inherited demyelinating Resulting from such genomic rearrangement may be categorized as genomic disorders in contrast to classic Mendelian diseasesĬaused by point mutations in the causative genes (for review, see Lupski 1998b Shaffer and Lupski 2000).Ĭharcot-Marie-Tooth disease type 1A (CMT1A) is one of the first and best-characterized examples of a submicroscopic genomicĭisorder. TheseĪre not visible by conventional karyotype assays and are thus likely to involve rearranged fragments smaller than 1–2 Mb.ĭisorders with these types of rearrangements may be caused by dosage effects of a single or multiple genes. Submicroscopic duplications/deletions represent genomic rearrangements that can be responsible for inherited diseases. The genomic region adjacent to proximal CMT1A–REP indicated an evolutionary mechanism for the formation of proximal CMT1A–REPĪnd the creation of novel genes by DNA rearrangement during primate speciation.

Most of these predicted genes are expressed only in embryonic stages. New genes ( TEKT3, HS3ST3B1, NPD008/CGI-148, CDRT1, and CDRT15) and 13 predicted genes were identified. In addition to three previously described genes, five Recombination frequency in males may enable a chromosomal misalignment at proximal and distal CMT1A–REPs and promote unequalĬrossing over, which occurs 10 times more frequently in male meiosis. The sexes with a lower recombination frequency in males (0.67 cM/Mb) versus females (5.5 cM/Mb). Comparison between physical and genetic maps revealed a striking difference in recombination rates between A low copy number repeat (LCR) was identified, with one copy inside and two copies outside In this region, we constructed PAC and BAC contigs and determined the complete nucleotide sequence. To delineate genomic structural features, investigate higher-order genomic architecture, and identify genes Genomic structure of the 1.4-Mb region, including other genes contained within the rearranged genomic segment, remains essentially Genomic disorders wherein unique genome architectural features result in susceptibility to DNA rearrangements that cause disease.Ī gene within the 1.4-Mb region, PMP22, is responsible for these disorders through a gene-dosage effect in the heterozygous duplication or deletion. Type 1A (CMT1A) and hereditary neuropathy with liability to pressure palsy (HNPP). Represent frequent genomic rearrangements resulting in two common inherited peripheral neuropathies, Charcot-Marie-Tooth disease

Duplication and deletion of the 1.4-Mb region in 17p12 that is delimited by two 24-kb low copy number repeats (CMT1A–REPs)

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