TY - JOUR
T1 - The Charcot-Marie-Tooth binary repeat contains a gene transcribed from the opposite strand of a partially duplicated region of the COX10 gene
AU - Kennerson, Marina L.
AU - Nassif, Najah T.
AU - Dawkins, Jennifer L.
AU - DeKroon, Robert M.
AU - Yang, Jian G.
AU - Nicholson, Garth A.
PY - 1997/11/15
Y1 - 1997/11/15
N2 - Misalignment between the two elements of the CMT1A-REP binary repeat on chromosome 17p11.2-p12 causes two inherited peripheral neuropathies, Charcot- Marie-Tooth type 1A (CMT1A) and hereditary neuropathy with liability to pressure palsies. This binary repeat contains repetitive DNA elements that include LINES, SINES, medium reiteration frequency repeats, and a transposon- like element. The COX10 gene has been mapped 10 kb centromeric to the distal CMT1A-REP element, and a portion of this gene is present in both the proximal end the distal CMT1A-REP elements. We report the isolation and characterization of a novel cDNA (C170RF1), which maps centromeric to and partially within the proximal CMT1A-REP element. Part of C170RF1 is transcribed from the opposite strand of the COX10 partial gene duplication present in the proximal CMT1A-REP element. This finding shows that C170RF1 and COX10 are being transcribed from opposite strands of identical DNA sequences that are separated by 1.5 Mb in the genome. RT-PCR analysis showed the proximal transcript was expressed in skeletal muscle. Sequence analysis identified an open reading frame encoding a 199-Amino-acid protein. Zoo blot analysis showed that the transcript is conserved in nonhuman primates. The presence of a binary repeat contributes to the instability of this region of chromosome 17, yet two CMT1A-REP elements are present in the chimpanzee and all human populations. The presence of expressed sequences in both elements of the CMT1A-REP binary repeat could explain the maintenance of this repeat in humans.
AB - Misalignment between the two elements of the CMT1A-REP binary repeat on chromosome 17p11.2-p12 causes two inherited peripheral neuropathies, Charcot- Marie-Tooth type 1A (CMT1A) and hereditary neuropathy with liability to pressure palsies. This binary repeat contains repetitive DNA elements that include LINES, SINES, medium reiteration frequency repeats, and a transposon- like element. The COX10 gene has been mapped 10 kb centromeric to the distal CMT1A-REP element, and a portion of this gene is present in both the proximal end the distal CMT1A-REP elements. We report the isolation and characterization of a novel cDNA (C170RF1), which maps centromeric to and partially within the proximal CMT1A-REP element. Part of C170RF1 is transcribed from the opposite strand of the COX10 partial gene duplication present in the proximal CMT1A-REP element. This finding shows that C170RF1 and COX10 are being transcribed from opposite strands of identical DNA sequences that are separated by 1.5 Mb in the genome. RT-PCR analysis showed the proximal transcript was expressed in skeletal muscle. Sequence analysis identified an open reading frame encoding a 199-Amino-acid protein. Zoo blot analysis showed that the transcript is conserved in nonhuman primates. The presence of a binary repeat contributes to the instability of this region of chromosome 17, yet two CMT1A-REP elements are present in the chimpanzee and all human populations. The presence of expressed sequences in both elements of the CMT1A-REP binary repeat could explain the maintenance of this repeat in humans.
UR - http://www.scopus.com/inward/record.url?scp=0031573383&partnerID=8YFLogxK
U2 - 10.1006/geno.1997.5012
DO - 10.1006/geno.1997.5012
M3 - Article
C2 - 9403059
AN - SCOPUS:0031573383
SN - 0888-7543
VL - 46
SP - 61
EP - 69
JO - Genomics
JF - Genomics
IS - 1
ER -