LINKAGE DISEQUILIBRIUM AND HAPLOTYPE ANALYSIS AMONG POLISH FAMILIES WITH SPINAL MUSCULAR-ATROPHY

Spinal Muscular Atrophy (SMA) is an inherited degenerative disorder of anterior horn cells that results in progressive muscle weakness and a trophy. The autosomal recessive forms of childhood-onset SMA have been mapped to chromosome 5q11.2-13.3, in a number of studies examining di fferent populations. A total of 9 simple sequence repeat markers were genotyped against 32 Polish families with SMA. The markers span an sim ilar to 0.7 cM region defined by the SMA flanking markers D5S435 and M AP1B. Significant linkage disequilibrium (corrected P < .05) was detec ted at four of these markers, with D/D-max values of less than or equa l to.83. Extended haplotype analysis revealed a predominant haplotype associated with SMA. The apparently high mutation rate of some of the markers has resulted in a number of haplotypes that vary slightly from this predominant haplotype. The predominant haplotype and these close ly related patterns represent 25% of the disease chromosomes and none of the nontransmitted parental chromosomes. This predominant haplotype is present both in patients with acute (type I) and in chronic (types II and III) forms of SMA and occurs twice in a homozygous state, both times in children with chronic SMA.