Allelic association and extended haplotype analysis of the spinal muscular atrophy (SMA) candidate region in the French Candadian population
- Ste-Justine Hospital, Quebec (Canada)
SMA is a common lower motor neuron disease characterized by progressive proximal limb and trunk muscle weakness. Despite the wide range in phenotypic severity, all three clinical types of childhood SMAs map to chromosome 5q11.2-5q13.3. The proximal (D5S557) flanking markers span about 1 Mb. We have previously demonstrated significant linkage disequilibrium between D5S125, D5S435, D5S351, JK53CA1/2 and SMA in the French Canadian population. We now present data for three new DNA markers mapping between D5S435 and D5S557 kindly provided to us by Drs. B. Wirth (A31), A. Burghes (Ag1) and A. MacKenzie (CATT-40G1). We identified 10 different A31 Alleles whose frequencies were similar for both normal and SMA chromosomes. Ag1 is a complex multi-allelic marker and specific primers amplified 1 (Class I), 2 or rarely 3 (Class II) alleles per chromosome. We observed significant association between Ag1 and SMA. For example, the 100 bp Ag1 fragment was typed on 20 of 73 SMA chromosomes and 0 of 74 normal chromosomes (p=<10{sup -4}). We also observed significant association between Ag1 Class genotypes and phenotypic severity. Class I chromosomes predominated in Type I SMA (p=.001) while Type II SMA individuals were generally heterozygous Class I/Class II (p=.001). Finally, we provide evidence for allelic association between Type I SMA and CATT-40G1, a tri-allelic sublocus of CATT-1. All of our Type I SMA chromosomes (n=20) carried a null allele compared to 40% of normal chromosomes (p=<10{sup -4}). Extended haplotype analyses indicated that > 19% of French Canadian SMA chromosomes appear to be ancestrally related to two unique haplotypes indicating their utility for linkage disequilibrium mapping.
- OSTI ID:
- 134118
- Report Number(s):
- CONF-941009-; ISSN 0002-9297; TRN: 95:005313-0854
- 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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