Linkage studies in spinocerebellar ataxia (SCA)

Abstract

Data are now available on 9 pedigrees in detail and 4 pedigrees as lod scores only. Linkage to HLA is significant (Z = 5.53 at recombination rates of 0.223 in males and 0.327 in females). Tight linkage is excluded. Nine pedigrees which appear to be typical olivopontocerebellar atrophy (OPCA I) have recombination rates of 0.150 in males and 0.300 in females. The remaining 4 pedigrees are clinically atypical or include discrepant data and give no evidence for linkage. The symbol SCA1 is proposed for a locus on chromosome 6 (loosely linked to HLA), at which at least one allele produces OPCA I (Menzel type). It is not yet clear whether other clinical types are determined by alleles at different loci, although this is suggested by several pedigrees, including a Danish pedigree of OPCA with dementia. Linkage evidence will be decisive in delineating the ataxias.

Linkage studies on glyoxalase I (<i>GLO</i>), pepsinogen (<i>PG</i>), spinocerebellar ataxia (<i>SCA1</i>), and <i>HLA</i>

“…Although this ignores some of the information, the lod scores are very close to those obtained by Morton et al (1980) who defined age specific affection risks. It is clear that heterogeneity among the C, O, A, and W-D families is not significant for either H LA -SC A 1 (yi2 = 2.13) or GLO-SCAI (y:i2 = 1.95).…”

Report of the committee on the genetic constitution of chromosome 6

“…Locus , 1991Persichetti et al, 1991Johnson et al, 1991Volz et al, 1991Frontali et al, 1991bZoghbi et al, 1991Ranum et al, 1991bAuburger et al, 1990Zoghbi et al, 1989Rich et al, 1987Wilkic et al, 1987Kanazawa et al, 1987Zoghbi et al, 1987Haines and Trofaitcr, 1986Haines et al, 1984Morton et al, 1980Jackson et al, 1977Yakuraetal., 1974 Abbal et al, 1987Welch et al, 1986Wilton and Charlton, 1986Carroll et al, 1984Olaisen et al, 1984Morley and Campbell, 1984O'Brien et al, 1983Allen, 1974 6p21. Carroll et al, 1987Bentley, 1986Wilton and Charlton, 1986Bentley and Porter, 1984Carroll et al, 1984Olaisen et al, 1984O'Brien et al, 1983Alper, 1976Day et al, 1975 6p21.…”

Report of the committee on the genetic constitution of chromosome 6

“…These include 13 loci confirmed at the time of Human Gene Mapping 5 (1979) plus SC AI, a locus for olivopontocerebellar ataxia (OPCA1, Menzel type), which had been provisionally assigned to chromosome 6. Data presented by Nino et al (1980), Pe dersen et al (1980), and Morton et al (1980) provide confirmation of linkage between HLA and SC AI (Jackson et al, 1977). However, not all cerebellar ataxia families show linkage with HLA (Morion et al, 1980;Pedersen et al, 1980); nine families with the HLA-linked variety have a total lod score of 7.7 at a male recombina tion frequency of 15%» and a female recom bination frequency of 30% (Morton et al, 1980).…”

“…Data presented by Nino et al (1980), Pe dersen et al (1980), and Morton et al (1980) provide confirmation of linkage between HLA and SC AI (Jackson et al, 1977). However, not all cerebellar ataxia families show linkage with HLA (Morion et al, 1980;Pedersen et al, 1980); nine families with the HLA-linked variety have a total lod score of 7.7 at a male recombina tion frequency of 15%» and a female recom bination frequency of 30% (Morton et al, 1980). Among the seven remaining assignments listed as provisional in H uman Gene Map ping 5 (1979), confirmation is not yet avail able concerning the loci for the receptor(s) for complement components, C3BR and C3DR, plasminogen activator (PLA), a receptor for monkey red blood cells (MRBC), a cell surface antigen (S5), hyper cholesterolemia with xanthomatosis (HC), and the P blood group.…”