Quantification, by solid-phase minisequencing, of the telomeric and centromeric copies of the survival motor neuron gene in families with spinal muscular atrophy

M Schwartz, N Sørensen, F J Hansen, Jens Michael Hertz, S Nørby, L Tranebjaerg, F Skovby

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

In an analysis of 30 families affected by spinal muscular atrophy (SMA) we have used the solid-phase minisequencing method to determine the ratio between the number of telomeric and centromeric copies of the survival motor neuron gene (SMN and cBCD541 respectively) on normal and SMA chromosomes. This has enabled us to establish haplotypes with regard to SMN and cBCD541, and estimate their frequencies, on both types of chromosomes. Six predominant haplotypes were identified, three for normal chromosomes and three for SMA chromosomes, characterized by having 0, 1, or 2 copies, respectively, of cBCD541. We found evidence for the presence of patients homozygous for a deletion of SMN and with only one copy of cBCD541, but found none deleted for all copies of this gene. Several asymptomatic carriers of SMA with only a single copy of SMN and no copy of cBCD541 were identified. We could not confirm the hypothesis that the presence of more copies of cBCD541 is correlated to a less severe course of the disease. The frequencies of haplotypes characterized by having 0, 1, or 2 copies, respectively, of cBCD541 were found to differ significantly between normal and SMA chromosomes. This distribution can be explained by an underrepresentation of the haplotype completely lacking SMN genes, which is expected to cause early embryonic death in homozygotes. This first report of a direct haplotype analysis of SMN and cBCD541 should help clarify the role of cBCD541 in the pathogenesis of SMA.
OriginalsprogEngelsk
TidsskriftHuman Molecular Genetics
Vol/bind6
Udgave nummer1
Sider (fra-til)99-104
Antal sider6
ISSN0964-6906
StatusUdgivet - 1997

Fingeraftryk

Motor Neurons
Haplotypes
Homozygote

Citer dette

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title = "Quantification, by solid-phase minisequencing, of the telomeric and centromeric copies of the survival motor neuron gene in families with spinal muscular atrophy",
abstract = "In an analysis of 30 families affected by spinal muscular atrophy (SMA) we have used the solid-phase minisequencing method to determine the ratio between the number of telomeric and centromeric copies of the survival motor neuron gene (SMN and cBCD541 respectively) on normal and SMA chromosomes. This has enabled us to establish haplotypes with regard to SMN and cBCD541, and estimate their frequencies, on both types of chromosomes. Six predominant haplotypes were identified, three for normal chromosomes and three for SMA chromosomes, characterized by having 0, 1, or 2 copies, respectively, of cBCD541. We found evidence for the presence of patients homozygous for a deletion of SMN and with only one copy of cBCD541, but found none deleted for all copies of this gene. Several asymptomatic carriers of SMA with only a single copy of SMN and no copy of cBCD541 were identified. We could not confirm the hypothesis that the presence of more copies of cBCD541 is correlated to a less severe course of the disease. The frequencies of haplotypes characterized by having 0, 1, or 2 copies, respectively, of cBCD541 were found to differ significantly between normal and SMA chromosomes. This distribution can be explained by an underrepresentation of the haplotype completely lacking SMN genes, which is expected to cause early embryonic death in homozygotes. This first report of a direct haplotype analysis of SMN and cBCD541 should help clarify the role of cBCD541 in the pathogenesis of SMA.",
keywords = "Centromere, Cyclic AMP Response Element-Binding Protein, Female, Gene Dosage, Genes, Humans, Male, Muscular Atrophy, Spinal, Nerve Tissue Proteins, Pedigree, Polymerase Chain Reaction, RNA-Binding Proteins, SMN Complex Proteins, Telomere",
author = "M Schwartz and N S{\o}rensen and Hansen, {F J} and Hertz, {Jens Michael} and S N{\o}rby and L Tranebjaerg and F Skovby",
year = "1997",
language = "English",
volume = "6",
pages = "99--104",
journal = "Human Molecular Genetics",
issn = "0964-6906",
publisher = "Heinemann",
number = "1",

}

Quantification, by solid-phase minisequencing, of the telomeric and centromeric copies of the survival motor neuron gene in families with spinal muscular atrophy. / Schwartz, M; Sørensen, N; Hansen, F J; Hertz, Jens Michael; Nørby, S; Tranebjaerg, L; Skovby, F.

I: Human Molecular Genetics, Bind 6, Nr. 1, 1997, s. 99-104.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Quantification, by solid-phase minisequencing, of the telomeric and centromeric copies of the survival motor neuron gene in families with spinal muscular atrophy

AU - Schwartz, M

AU - Sørensen, N

AU - Hansen, F J

AU - Hertz, Jens Michael

AU - Nørby, S

AU - Tranebjaerg, L

AU - Skovby, F

PY - 1997

Y1 - 1997

N2 - In an analysis of 30 families affected by spinal muscular atrophy (SMA) we have used the solid-phase minisequencing method to determine the ratio between the number of telomeric and centromeric copies of the survival motor neuron gene (SMN and cBCD541 respectively) on normal and SMA chromosomes. This has enabled us to establish haplotypes with regard to SMN and cBCD541, and estimate their frequencies, on both types of chromosomes. Six predominant haplotypes were identified, three for normal chromosomes and three for SMA chromosomes, characterized by having 0, 1, or 2 copies, respectively, of cBCD541. We found evidence for the presence of patients homozygous for a deletion of SMN and with only one copy of cBCD541, but found none deleted for all copies of this gene. Several asymptomatic carriers of SMA with only a single copy of SMN and no copy of cBCD541 were identified. We could not confirm the hypothesis that the presence of more copies of cBCD541 is correlated to a less severe course of the disease. The frequencies of haplotypes characterized by having 0, 1, or 2 copies, respectively, of cBCD541 were found to differ significantly between normal and SMA chromosomes. This distribution can be explained by an underrepresentation of the haplotype completely lacking SMN genes, which is expected to cause early embryonic death in homozygotes. This first report of a direct haplotype analysis of SMN and cBCD541 should help clarify the role of cBCD541 in the pathogenesis of SMA.

AB - In an analysis of 30 families affected by spinal muscular atrophy (SMA) we have used the solid-phase minisequencing method to determine the ratio between the number of telomeric and centromeric copies of the survival motor neuron gene (SMN and cBCD541 respectively) on normal and SMA chromosomes. This has enabled us to establish haplotypes with regard to SMN and cBCD541, and estimate their frequencies, on both types of chromosomes. Six predominant haplotypes were identified, three for normal chromosomes and three for SMA chromosomes, characterized by having 0, 1, or 2 copies, respectively, of cBCD541. We found evidence for the presence of patients homozygous for a deletion of SMN and with only one copy of cBCD541, but found none deleted for all copies of this gene. Several asymptomatic carriers of SMA with only a single copy of SMN and no copy of cBCD541 were identified. We could not confirm the hypothesis that the presence of more copies of cBCD541 is correlated to a less severe course of the disease. The frequencies of haplotypes characterized by having 0, 1, or 2 copies, respectively, of cBCD541 were found to differ significantly between normal and SMA chromosomes. This distribution can be explained by an underrepresentation of the haplotype completely lacking SMN genes, which is expected to cause early embryonic death in homozygotes. This first report of a direct haplotype analysis of SMN and cBCD541 should help clarify the role of cBCD541 in the pathogenesis of SMA.

KW - Centromere

KW - Cyclic AMP Response Element-Binding Protein

KW - Female

KW - Gene Dosage

KW - Genes

KW - Humans

KW - Male

KW - Muscular Atrophy, Spinal

KW - Nerve Tissue Proteins

KW - Pedigree

KW - Polymerase Chain Reaction

KW - RNA-Binding Proteins

KW - SMN Complex Proteins

KW - Telomere

M3 - Journal article

VL - 6

SP - 99

EP - 104

JO - Human Molecular Genetics

JF - Human Molecular Genetics

SN - 0964-6906

IS - 1

ER -