High-density single nucleotide polymorphism screen in a large multiplex neural tube defect family refines linkage to loci at 7p21.1-pter and 2q33.1-q35

Demetra S. Stamm, Evadnie Rampersaud, Susan H. Slifer, Lorraine Mehltretter, Deborah G. Siegel, Jianzhen Xie, Diane Hu-Lince, David W. Craig, Dietrich A. Stephan, Timothy M. George, John Gilbert, Marcy C. Speer, Joanna Aben, Arthur Aylsworth, Cynthia Powell, Joanne Mackey, Gordon Worley, Timothy Brei, Connie Buran, Joann BodurthaKathleen Sawin, Philip Mack, Elli Meeropol, Nicole Lasarsky, David McLone, Joy Ito, W. Jerry Oakes, Marion Walker, Bermans Iskandar

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

BACKGROUND: Neural tube defects (NTDs) are considered complex, with both genetic and environmental factors implicated. To date, no major causative genes have been identified in humans despite several investigations. The first genomewide screen in NTDs demonstrated evidence of linkage to chromosomes 7 and 10. This screen included 44 multiplex families and consisted of 402 microsatellite markers spaced ∼10 cM apart. Further investigation of the genomic screen data identified a single large multiplex family, pedigree 8776, as primarily driving the linkage results on chromosome 7. METHODS: To investigate this family more thoroughly, a high-density single nucleotide polymorphism (SNP) screen was performed. Two-point and multipoint linkage analyses were performed using both parametric and nonparametric methods. RESULTS: For both the microsatellite and SNP markers, linkage analysis suggested the involvement of a locus or loci proximal to the telomeric regions of chromosomes 2q and 7p, with both regions generating a LOD* score of ∼3.0 using a nonparametric identity by descent relative sharing method. CONCLUSIONS: The regions with the strongest evidence for linkage map proximal to the telomeres on these two chromosomes. In addition to mutations and/or variants in a major gene, these loci may harbor a microdeletion and/or translocation; potentially, polygenic factors may also be involved. This single family may be promising for narrowing the search for NTD susceptibility genes.

Original languageEnglish
Pages (from-to)499-505
Number of pages7
JournalBirth Defects Research Part A - Clinical and Molecular Teratology
Volume76
Issue number6
DOIs
StatePublished - Jun 1 2006
Externally publishedYes

Fingerprint

Neural Tube Defects
Single Nucleotide Polymorphism
Chromosomes, Human, Pair 7
Microsatellite Repeats
Chromosomes
Genes
Chromosomes, Human, Pair 10
Telomere
Pedigree
Mutation

Keywords

  • Genetic mapping
  • Genome screen
  • Linkage
  • Neural tube defects
  • NTDs
  • Spina bifida

ASJC Scopus subject areas

  • Developmental Biology

Cite this

High-density single nucleotide polymorphism screen in a large multiplex neural tube defect family refines linkage to loci at 7p21.1-pter and 2q33.1-q35. / Stamm, Demetra S.; Rampersaud, Evadnie; Slifer, Susan H.; Mehltretter, Lorraine; Siegel, Deborah G.; Xie, Jianzhen; Hu-Lince, Diane; Craig, David W.; Stephan, Dietrich A.; George, Timothy M.; Gilbert, John; Speer, Marcy C.; Aben, Joanna; Aylsworth, Arthur; Powell, Cynthia; Mackey, Joanne; Worley, Gordon; Brei, Timothy; Buran, Connie; Bodurtha, Joann; Sawin, Kathleen; Mack, Philip; Meeropol, Elli; Lasarsky, Nicole; McLone, David; Ito, Joy; Oakes, W. Jerry; Walker, Marion; Iskandar, Bermans.

In: Birth Defects Research Part A - Clinical and Molecular Teratology, Vol. 76, No. 6, 01.06.2006, p. 499-505.

Research output: Contribution to journalArticle

Stamm, DS, Rampersaud, E, Slifer, SH, Mehltretter, L, Siegel, DG, Xie, J, Hu-Lince, D, Craig, DW, Stephan, DA, George, TM, Gilbert, J, Speer, MC, Aben, J, Aylsworth, A, Powell, C, Mackey, J, Worley, G, Brei, T, Buran, C, Bodurtha, J, Sawin, K, Mack, P, Meeropol, E, Lasarsky, N, McLone, D, Ito, J, Oakes, WJ, Walker, M & Iskandar, B 2006, 'High-density single nucleotide polymorphism screen in a large multiplex neural tube defect family refines linkage to loci at 7p21.1-pter and 2q33.1-q35', Birth Defects Research Part A - Clinical and Molecular Teratology, vol. 76, no. 6, pp. 499-505. https://doi.org/10.1002/bdra.20272
Stamm, Demetra S. ; Rampersaud, Evadnie ; Slifer, Susan H. ; Mehltretter, Lorraine ; Siegel, Deborah G. ; Xie, Jianzhen ; Hu-Lince, Diane ; Craig, David W. ; Stephan, Dietrich A. ; George, Timothy M. ; Gilbert, John ; Speer, Marcy C. ; Aben, Joanna ; Aylsworth, Arthur ; Powell, Cynthia ; Mackey, Joanne ; Worley, Gordon ; Brei, Timothy ; Buran, Connie ; Bodurtha, Joann ; Sawin, Kathleen ; Mack, Philip ; Meeropol, Elli ; Lasarsky, Nicole ; McLone, David ; Ito, Joy ; Oakes, W. Jerry ; Walker, Marion ; Iskandar, Bermans. / High-density single nucleotide polymorphism screen in a large multiplex neural tube defect family refines linkage to loci at 7p21.1-pter and 2q33.1-q35. In: Birth Defects Research Part A - Clinical and Molecular Teratology. 2006 ; Vol. 76, No. 6. pp. 499-505.
@article{c8661d30d870400f849761994aaae197,
title = "High-density single nucleotide polymorphism screen in a large multiplex neural tube defect family refines linkage to loci at 7p21.1-pter and 2q33.1-q35",
abstract = "BACKGROUND: Neural tube defects (NTDs) are considered complex, with both genetic and environmental factors implicated. To date, no major causative genes have been identified in humans despite several investigations. The first genomewide screen in NTDs demonstrated evidence of linkage to chromosomes 7 and 10. This screen included 44 multiplex families and consisted of 402 microsatellite markers spaced ∼10 cM apart. Further investigation of the genomic screen data identified a single large multiplex family, pedigree 8776, as primarily driving the linkage results on chromosome 7. METHODS: To investigate this family more thoroughly, a high-density single nucleotide polymorphism (SNP) screen was performed. Two-point and multipoint linkage analyses were performed using both parametric and nonparametric methods. RESULTS: For both the microsatellite and SNP markers, linkage analysis suggested the involvement of a locus or loci proximal to the telomeric regions of chromosomes 2q and 7p, with both regions generating a LOD* score of ∼3.0 using a nonparametric identity by descent relative sharing method. CONCLUSIONS: The regions with the strongest evidence for linkage map proximal to the telomeres on these two chromosomes. In addition to mutations and/or variants in a major gene, these loci may harbor a microdeletion and/or translocation; potentially, polygenic factors may also be involved. This single family may be promising for narrowing the search for NTD susceptibility genes.",
keywords = "Genetic mapping, Genome screen, Linkage, Neural tube defects, NTDs, Spina bifida",
author = "Stamm, {Demetra S.} and Evadnie Rampersaud and Slifer, {Susan H.} and Lorraine Mehltretter and Siegel, {Deborah G.} and Jianzhen Xie and Diane Hu-Lince and Craig, {David W.} and Stephan, {Dietrich A.} and George, {Timothy M.} and John Gilbert and Speer, {Marcy C.} and Joanna Aben and Arthur Aylsworth and Cynthia Powell and Joanne Mackey and Gordon Worley and Timothy Brei and Connie Buran and Joann Bodurtha and Kathleen Sawin and Philip Mack and Elli Meeropol and Nicole Lasarsky and David McLone and Joy Ito and Oakes, {W. Jerry} and Marion Walker and Bermans Iskandar",
year = "2006",
month = "6",
day = "1",
doi = "10.1002/bdra.20272",
language = "English",
volume = "76",
pages = "499--505",
journal = "Teratology",
issn = "1542-0752",
publisher = "Wiley-Liss Inc.",
number = "6",

}

TY - JOUR

T1 - High-density single nucleotide polymorphism screen in a large multiplex neural tube defect family refines linkage to loci at 7p21.1-pter and 2q33.1-q35

AU - Stamm, Demetra S.

AU - Rampersaud, Evadnie

AU - Slifer, Susan H.

AU - Mehltretter, Lorraine

AU - Siegel, Deborah G.

AU - Xie, Jianzhen

AU - Hu-Lince, Diane

AU - Craig, David W.

AU - Stephan, Dietrich A.

AU - George, Timothy M.

AU - Gilbert, John

AU - Speer, Marcy C.

AU - Aben, Joanna

AU - Aylsworth, Arthur

AU - Powell, Cynthia

AU - Mackey, Joanne

AU - Worley, Gordon

AU - Brei, Timothy

AU - Buran, Connie

AU - Bodurtha, Joann

AU - Sawin, Kathleen

AU - Mack, Philip

AU - Meeropol, Elli

AU - Lasarsky, Nicole

AU - McLone, David

AU - Ito, Joy

AU - Oakes, W. Jerry

AU - Walker, Marion

AU - Iskandar, Bermans

PY - 2006/6/1

Y1 - 2006/6/1

N2 - BACKGROUND: Neural tube defects (NTDs) are considered complex, with both genetic and environmental factors implicated. To date, no major causative genes have been identified in humans despite several investigations. The first genomewide screen in NTDs demonstrated evidence of linkage to chromosomes 7 and 10. This screen included 44 multiplex families and consisted of 402 microsatellite markers spaced ∼10 cM apart. Further investigation of the genomic screen data identified a single large multiplex family, pedigree 8776, as primarily driving the linkage results on chromosome 7. METHODS: To investigate this family more thoroughly, a high-density single nucleotide polymorphism (SNP) screen was performed. Two-point and multipoint linkage analyses were performed using both parametric and nonparametric methods. RESULTS: For both the microsatellite and SNP markers, linkage analysis suggested the involvement of a locus or loci proximal to the telomeric regions of chromosomes 2q and 7p, with both regions generating a LOD* score of ∼3.0 using a nonparametric identity by descent relative sharing method. CONCLUSIONS: The regions with the strongest evidence for linkage map proximal to the telomeres on these two chromosomes. In addition to mutations and/or variants in a major gene, these loci may harbor a microdeletion and/or translocation; potentially, polygenic factors may also be involved. This single family may be promising for narrowing the search for NTD susceptibility genes.

AB - BACKGROUND: Neural tube defects (NTDs) are considered complex, with both genetic and environmental factors implicated. To date, no major causative genes have been identified in humans despite several investigations. The first genomewide screen in NTDs demonstrated evidence of linkage to chromosomes 7 and 10. This screen included 44 multiplex families and consisted of 402 microsatellite markers spaced ∼10 cM apart. Further investigation of the genomic screen data identified a single large multiplex family, pedigree 8776, as primarily driving the linkage results on chromosome 7. METHODS: To investigate this family more thoroughly, a high-density single nucleotide polymorphism (SNP) screen was performed. Two-point and multipoint linkage analyses were performed using both parametric and nonparametric methods. RESULTS: For both the microsatellite and SNP markers, linkage analysis suggested the involvement of a locus or loci proximal to the telomeric regions of chromosomes 2q and 7p, with both regions generating a LOD* score of ∼3.0 using a nonparametric identity by descent relative sharing method. CONCLUSIONS: The regions with the strongest evidence for linkage map proximal to the telomeres on these two chromosomes. In addition to mutations and/or variants in a major gene, these loci may harbor a microdeletion and/or translocation; potentially, polygenic factors may also be involved. This single family may be promising for narrowing the search for NTD susceptibility genes.

KW - Genetic mapping

KW - Genome screen

KW - Linkage

KW - Neural tube defects

KW - NTDs

KW - Spina bifida

UR - http://www.scopus.com/inward/record.url?scp=33748285273&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33748285273&partnerID=8YFLogxK

U2 - 10.1002/bdra.20272

DO - 10.1002/bdra.20272

M3 - Article

C2 - 16933213

AN - SCOPUS:33748285273

VL - 76

SP - 499

EP - 505

JO - Teratology

JF - Teratology

SN - 1542-0752

IS - 6

ER -