SNPs in the neural cell adhesion molecule 1 gene (NCAM1) may be associated with human neural tube defects

Kristen L Deak; Abee L Boyles; Heather C Etchevers; Elizabeth C Melvin; Deborah G Siegel; Felicia L Graham; Susan H Slifer; David S Enterline; Timothy M George; Michel Vekemans; David McClay; Alexander G Bassuk; John A Kessler; Elwood Linney; John R Gilbert; Marcy C Speer

doi:10.1007/s00439-005-1299-7

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SNPs in the neural cell adhesion molecule 1 gene (NCAM1) may be associated with human neural tube defects

Journal article

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SNPs in the neural cell adhesion molecule 1 gene (NCAM1) may be associated with human neural tube defects

Kristen L Deak, Abee L Boyles, Heather C Etchevers, Elizabeth C Melvin, Deborah G Siegel, Felicia L Graham, Susan H Slifer, David S Enterline, Timothy M George, Michel Vekemans, …

Human genetics, Vol.117(2-3), pp.133-142

07/2005

DOI: 10.1007/s00439-005-1299-7

PMCID: PMC3130962

PMID: 15883837

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https://www.ncbi.nlm.nih.gov/pmc/articles/3130962View

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Abstract

Neural tube defects (NTDs) are common birth defects, occurring in approximately 1/1,000 births; both genetic and environmental factors are implicated. To date, no major genetic risk factors have been identified. Throughout development, cell adhesion molecules are strongly implicated in cell–cell interactions, and may play a role in the formation and closure of the neural tube. To evaluate the role of neural cell adhesion molecule 1 (NCAM1) in risk of human NTDs, we screened for novel single-nucleotide polymorphisms (SNPs) within the gene. Eleven SNPs across NCAM1 were genotyped using TaqMan. We utilized a family-based approach to evaluate evidence for association and/or linkage disequilibrium. We evaluated American Caucasian simplex lumbosacral myelomeningocele families ( n =132 families) using the family based association test (FBAT) and the pedigree disequilibrium test (PDT). Association analysis revealed a significant association between risk for NTDs and intronic SNP rs2298526 using both the FBAT test ( P =0.0018) and the PDT ( P =0.0025). Using the HBAT version of the FBAT to look for haplotype association, all pairwise comparisons with SNP rs2298526 were also significant. A replication study set, consisting of 72 additional families showed no significant association; however, the overall trend for overtransmission of the less common allele of SNP rs2298526 remained significant in the combined sample set. In addition, we analyzed the expression pattern of the NCAM1 protein in human embryos, and while NCAM1 is not expressed within the neural tube at the time of closure, it is expressed in the surrounding and later in differentiated neurons of the CNS. These results suggest variations in NCAM1 may influence risk for human NTDs.

Details

Title: Subtitle: SNPs in the neural cell adhesion molecule 1 gene (NCAM1) may be associated with human neural tube defects
Creators: Kristen L Deak - Center for Human Genetics, Duke University Medical Center, Box 3445, Durham, NC 27710, USA
Abee L Boyles - Center for Human Genetics, Duke University Medical Center, Box 3445, Durham, NC 27710, USA
Heather C Etchevers - Département de Génétique Médicale and INSERM U393, Hôpital Necker, Paris, France
Elizabeth C Melvin - Center for Human Genetics, Duke University Medical Center, Box 3445, Durham, NC 27710, USA
Deborah G Siegel - Center for Human Genetics, Duke University Medical Center, Box 3445, Durham, NC 27710, USA
Felicia L Graham - Center for Human Genetics, Duke University Medical Center, Box 3445, Durham, NC 27710, USA
Susan H Slifer - Center for Human Genetics, Duke University Medical Center, Box 3445, Durham, NC 27710, USA
David S Enterline - Department of Radiology, Duke University Medical Center, Box 3808, Durham, NC 27710, USA
Timothy M George - Department of Surgery, Duke University Medical Center, Box 3272, Durham, NC 27710, USA
Michel Vekemans - Département de Génétique Médicale and INSERM U393, Hôpital Necker, Paris, France
David McClay - Department of Biology, Duke University Medical Center, Box 3445, Durham, NC 27710, USA
Alexander G Bassuk - Northwestern University’s Feinberg School of Medicine, Chicago, IL, USA
John A Kessler - Northwestern University’s Feinberg School of Medicine, Chicago, IL, USA
Elwood Linney - Department of Molecular Genetics and Microbiology, Duke University Medical Center, Box 3020, Durham, NC 27710, USA
John R Gilbert - Center for Human Genetics, Duke University Medical Center, Box 3445, Durham, NC 27710, USA
Marcy C Speer - Center for Human Genetics, Duke University Medical Center, Box 3445, Durham, NC 27710, USA
Resource Type: Journal article
Publication Details: Human genetics, Vol.117(2-3), pp.133-142
DOI: 10.1007/s00439-005-1299-7
PMID: 15883837
PMCID: PMC3130962
NLM abbreviation: Hum Genet
ISSN: 0340-6717
eISSN: 1432-1203
Grant note: R01 NS020013-26 || NS / National Institute of Neurological Disorders and Stroke : NINDS R01 NS020778-25 || NS / National Institute of Neurological Disorders and Stroke : NINDS
Language: English
Date published: 07/2005
Academic Unit: Neurology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Neurology (Pediatrics)
Record Identifier: 9984020607902771

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