Isolation and characterization of human cerebellum cDNAs containing polymorphic CAG trinucleotide repeats
- Niigata Univ. (Japan); and others
It has been discovered that neurologic diseases such as X linked spinal and bulbar muscular atrophy, Huntington`s disease, spinocerebellar ataxia type 1 (SCA1), and dentatorubral-pallidoluysian atrophy (DRPLA) are caused by unstable expansions of CAG repeats, which shed a light on a new mechanism of human hereditary diseases. The genetic anticipation, a common genetic feature in these diseases, can be explained by the trinucleotide repeat expansions, and an inverse correlation between the ages of onset and the numbers of trinucleotide repeats is demonstrated in these diseases. Furthermore, there have been diseases such as spinocerebellar ataxia 2 (SCA2) and Machado-Joseph disease showing similar genetic anticipation, which suggests that their causative mutations are unstable expansions of trinucleotide repeats. To identify candidate genes for neurodegenerative diseases which are expressed in human cerebellum and contain CAG repeats, we screened a human cerebellum cDNA library with an oligonucleotide (CAG){sub 10}, labelled with [{gamma}{sup 32}P]ATP. Out of 78 clones we have isolated, 43 clones were partially sequenced and 31 clones were shown to contain CAG or CTG tinucleotide repeats. From homology searches, 12 of the 59 clones were identified to contain known sequences including human MAR/SAR DNA binding protein, human glial fibrillary acidic protein, human myelin transcription factor 1, human neuronal growth protein 43 and human myocyte-specific enhancer 2. From 6 clones out of the 43 novel genes, we were able to develop primer pairs flanking CAG repeats and determined chromosomal localizations with human and rodent hybrid mapping panels. These CAG repeats were shown to be polymorphic and mapped to 1, 15, 17 and 18. These novel cDNAs will be useful as candidate genes for hereditary neurologic diseases showing genetic anticipation.
- OSTI ID:
- 134034
- Report Number(s):
- CONF-941009-; ISSN 0002-9297; TRN: 95:005313-0770
- Journal Information:
- American Journal of Human Genetics, Vol. 55, Issue Suppl.3; Conference: 44. annual meeting of the American Society of Human Genetics, Montreal (Canada), 18-22 Oct 1994; Other Information: PBD: Sep 1994
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
BASIC STUDIES
HUMAN CHROMOSOMES
GENETIC MAPPING
GENES
PATIENTS
HEREDITARY DISEASES
NERVOUS SYSTEM DISEASES
AGE DEPENDENCE
NUCLEOTIDES
MUTATIONS
INSTABILITY
DNA-CLONING
DNA SEQUENCING
PROTEINS
TRANSCRIPTION FACTORS
HUMAN CHROMOSOME 1
HUMAN CHROMOSOME 15
HUMAN CHROMOSOME 17
HUMAN CHROMOSOME 18