title: An investigation of genetic heterogeneity and linkage disequilibrium in 161 families with spinal muscular atrophy.
abstract: We performed linkage analysis of 161 families with spinal muscular atrophy (SMA) in which affected individuals suffer from the intermediate or mild form of the disease (Types II or III). Markers for six loci encompassing the chromosome 5q11.2-q13.3 region were typed. The best map location for the disease locus was found to be between D5S6 and MAP1B. The corresponding 1 lod unit support intervals is confined to this interval and spans 0.5 cM. The data strongly support the hypothesis of linkage heterogeneity (likelihood ratio, 1.14 x 10(4)), with 5% of the families unlinked. Four families have a probability of less than 50% of segregating the SMA gene linked to the region 5q11.2-q13.3. A likelihood approach to test for linkage disequilibrium revealed no significant departure from Hardy-Weinberg equilibrium with any marker under study.
authors.affiliation: Department of Psychiatry, Columbia University, New York, New York 10032.
authors.forename: C
authors.initials: C
authors.lastname: Mérette
authors.forename: L M
authors.initials: LM
authors.lastname: Brzustowicz
authors.forename: R J
authors.initials: RJ
authors.lastname: Daniels
authors.forename: K E
authors.initials: KE
authors.lastname: Davies
authors.forename: T C
authors.initials: TC
authors.lastname: Gilliam
authors.forename: J
authors.initials: J
authors.lastname: Melki
authors.forename: A
authors.initials: A
authors.lastname: Munnich
authors.forename: M A
authors.initials: MA
authors.lastname: Pericak-Vance
authors.forename: T
authors.initials: T
authors.lastname: Siddique
authors.forename: B
authors.initials: B
authors.lastname: Voosen
mesh_terms: D000483:Alleles; D002874:Chromosome Mapping; D002895:Chromosomes, Human, Pair 5; D005260:Female; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium; D008126:Lod Score; D008297:Male; D009134:Muscular Atrophy, Spinal / Q000235:genetics*; D010375:Pedigree; D011110:Polymorphism, Genetic