Deletion mapping of the spinal muscular atrophy region
- Hopital des Enfants Malades, Paris (France); and others
Autosomal recessive childhood spinal muscular atrophies (SMA) are divided into severe (Type I) and mild forms (Types II and III). Using a combination of fine genetic and physical mapping, we constructed a YAC contig of the 5q13 region spanning the disease locus and showed the presence of low copy-repeats in this region. Allele segregation was analyzed at the closest genetic loci detected by markers C212 and C272 in 201 SMA families. Inherited and de novo deletions were observed in 9 unrelated SMA patients. Moreover, deletion events were statistically associated with type I SMA patients as shown by marked heterozygosity deficiency for the loci studied. Genetic analysis with all polymorphic DNA markers derived from the YAC contig has allowed to define the smallest rearrangement between the loci detected by C161 and the C212-C272-C171, covering a 1Mb interval. A large scale physical map of this region has been constructed using pulsed field gel electrophoresis (PFGE) and rare cutter restriction endonucleases. Comparison of the physical map has been established both in patients harboring deletions and unaffected controls using various anonymous probes derived from the YAC contig. This analysis has allowed us to define a physical interval in which at least a portion of the SMA gene must be located. Search for genes within this interval will contribute to the identification of the disease gene or genes.
- OSTI ID:
- 134388
- Report Number(s):
- CONF-941009-; ISSN 0002-9297; TRN: 95:005313-1122
- 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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