Cloning and expression of the rat atrophin-I (DRPLA disease gene) homologue.
Dentatorubral pallidoluysian atrophy (DRPLA) is a rare, progressive, fatal neuropsychiatric disorder similar to Huntington's disease, caused by an expansion of a CAG trinucleotide repeat encoding glutamine. We have cloned the cDNA of the rat homologue of this gene. The cDNA contains a 3549 base pair open reading frame that is 88.2% identical to the human cDNA, with a predicted amino acid sequence that is 93.6% identical to the human sequence. The consecutive glutamine repeat is only five residues in length (normal range in human: 7-35 glutamines) and is followed by a polymorphic region of alternating glutamine and proline residues (QQQQQPQPQPQPQQ). The sequence also includes a polymorphic proline repeat, a serine repeat, and a region of alternating acidic and basic residues. Northern analysis and in situ hybridization indicate that the gene is widely expressed as a 4.5 kb mRNA, with a neuronal distribution in the brain. The widespread expression of this gene is consistent with the possibility that DRPLA, like other glutamine repeat diseases, is a result of an abnormality at the protein level.
Loev
S J
SJ
Laboratory of Molecular Neurobiology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205-2196, USA.
Margolis
R L
RL
Young
W S
WS
Li
S H
SH
Schilling
G
G
Ashworth
R G
RG
Ross
C A
CA
D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D001927:Brain Diseases / Q000235:genetics*; D003001:Cloning, Molecular; D018076:DNA, Complementary; D015870:Gene Expression; D005973:Glutamine / Q000235:genetics; D006816:Huntington Disease / Q000235:genetics; D017403:In Situ Hybridization; D008969:Molecular Sequence Data; D017354:Point Mutation; D012333:RNA, Messenger; D051381:Rats; D017207:Rats, Sprague-Dawley; D018911:Trinucleotide Repeats
D018076:DNA, Complementary; D012333:RNA, Messenger; D005973:Glutamine