FISH detection of chromosome polymorphism and deletions in the spinal muscular atrophy (SMA) region of 5q13

• Published in: Cytogenetic and genome research Vol. 75; no. 4; pp. 243 - 247
• Main Authors: RAJCAN-SEPAROVIC, E, MAHADEVAN, M. S, LEFEBVRE, C, BESNER-JOHNSTON, A, IKEDA, J.-E, KORNELUK, R. G, MACKENZIE, A
• Format: Journal Article
• Language: English
• Published: Freiburg Karger 01.01.1996; Basel S. Karger AG; Paris
• Subjects: Biological and medical sciences; Chromosome Deletion; Chromosomes, Human, Pair 5 - genetics; Chromosomes, Human, Pair 5 - ultrastructure; Classical genetics, quantitative genetics, hybrids; Cyclic AMP Response Element-Binding Protein; Fundamental and applied biological sciences. Psychology; Gene Deletion; Genetics of eukaryotes. Biological and molecular evolution; Heterozygote; Human; Humans; In Situ Hybridization, Fluorescence; Muscular Atrophy, Spinal - genetics; Nerve Tissue Proteins - deficiency; Nerve Tissue Proteins - genetics; Neuronal Apoptosis-Inhibitory Protein; Polymorphism, Genetic; RNA-Binding Proteins; SMN Complex Proteins; Human; Neuromuscular diseases; Nervous system diseases; Spinal amyotrophy; Chromosome B5; Gene; Central nervous system disease; Cytogenetics; Deletion; Genetics; Degenerative disease; Mutation; Spinal cord disease; Polymorphism
• ISSN: 0301-0171; 1424-8581; 1424-859X
• DOI: 10.1159/000134493

The search for the SMA defect has culminated in the identification of two candidate 5q13.1 SMA genes, NAIP and SMN both of which are deleted in individuals with SMA. It was postulated that the intact and degenerate versions of NAIP are present in variable and frequently high copy numbers in this region while SMN was proposed to be present in only two copies. In order to assess the copy number of NAIP and SMN we have conducted interphase FISH analysis using NAIP and SMN gene-containing cosmid and plasmid probes. Our results confirm the variability in the number of NAIP signals in non-SMA chromosomes (2-6) and show that SMN is present on average twice per chromosome although in one chromosome 4-5 signals for the SMN-containing cosmid probe were detected. Our analysis reveals that one of four and three of six type I SMA chromosomes had a lower than normal number of NAIP and SMN signals, respectively. In two of six SMA type I chromosomes, complete loss of hybridization signal was observed on one chromosome 5 with our SMN cosmid probe possibly reflecting a large scale deletion. Large scale deletions were not detectable when metaphase chromosomes of an SMA type II and III patient were analyzed.