A custom 148 gene-based resequencing chip and the SNP explorer software: New tools to study antibody deficiency

Hong Ying Wang, Vivek Gopalan, Ivona Aksentijevich, Meredith Yeager, Chi Adrian Ma, Yasmin Ali Mohamoud, Mariam Quinones, Casey Matthews, Joseph Boland, Julie E. Niemela, Troy R. Torgerson, Silvia Giliani, Gulbu Uzel, Jordan S. Orange, Ralph Shapiro, Luigi Notarangelo, Hans D. Ochs, Thomas Fleisher, Daniel Kastner, Stephen J. ChanockAshish Jain

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Hyper-IgM syndrome and Common Variable Immunodeficiency are heterogeneous disorders characterized by a predisposition to serious infection and impaired or absent neutralizing antibody responses. Although a number of single gene defects have been associated with these immune deficiency disorders, the genetic basis of many cases is not known. To facilitate mutation screening in patients with these syndromes, we have developed a custom 300-kb resequencing array, the Hyper-IgM/CVID chip, which interrogates 1,576 coding exons and intron-exon junction regions from 148 genes implicated in B-cell development and immunoglobulin isotype switching. Genomic DNAs extracted from patients were hybridized to the array using a high-throughput protocol for target sequence amplification, pooling, and hybridization. A Web-based application, SNP Explorer, was developed to directly analyze and visualize the single nucleotide polymorphism (SNP) annotation and for quality filtering. Several mutations in known disease-susceptibility genes such as CD40LG, TNFRSF13B, IKBKG, AICDA, as well as rare nucleotide changes in other genes such as TRAF3IP2, were identified in patient DNA samples and validated by direct sequencing. We conclude that the Hyper-IgM/CVID chip combined with SNP Explorer may provide a cost-effective tool for high-throughput discovery of novel mutations among hundreds of disease-relevant genes in patients with inherited antibody deficiency.

Original languageEnglish
Pages (from-to)1080-1088
Number of pages9
JournalHuman Mutation
Volume31
Issue number9
DOIs
Publication statusPublished - 1 Sep 2010
Externally publishedYes

Fingerprint

Single Nucleotide Polymorphism
Software
Antibodies
Mutation
Genes
Immunoglobulin M
Exons
Hyper-IgM Immunodeficiency Syndrome
Immunoglobulin Class Switching
Common Variable Immunodeficiency
Inborn Genetic Diseases
Immunoglobulin Isotypes
DNA
Disease Susceptibility
Immune System Diseases
Neutralizing Antibodies
Introns
Antibody Formation
B-Lymphocytes
Nucleotides

Keywords

  • B cell
  • CVID
  • Hyper-IgM
  • Resequencing microarray
  • SNP
  • Somatic hypermutation

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

A custom 148 gene-based resequencing chip and the SNP explorer software : New tools to study antibody deficiency. / Wang, Hong Ying; Gopalan, Vivek; Aksentijevich, Ivona; Yeager, Meredith; Ma, Chi Adrian; Ali Mohamoud, Yasmin; Quinones, Mariam; Matthews, Casey; Boland, Joseph; Niemela, Julie E.; Torgerson, Troy R.; Giliani, Silvia; Uzel, Gulbu; Orange, Jordan S.; Shapiro, Ralph; Notarangelo, Luigi; Ochs, Hans D.; Fleisher, Thomas; Kastner, Daniel; Chanock, Stephen J.; Jain, Ashish.

In: Human Mutation, Vol. 31, No. 9, 01.09.2010, p. 1080-1088.

Research output: Contribution to journalArticle

Wang, HY, Gopalan, V, Aksentijevich, I, Yeager, M, Ma, CA, Ali Mohamoud, Y, Quinones, M, Matthews, C, Boland, J, Niemela, JE, Torgerson, TR, Giliani, S, Uzel, G, Orange, JS, Shapiro, R, Notarangelo, L, Ochs, HD, Fleisher, T, Kastner, D, Chanock, SJ & Jain, A 2010, 'A custom 148 gene-based resequencing chip and the SNP explorer software: New tools to study antibody deficiency', Human Mutation, vol. 31, no. 9, pp. 1080-1088. https://doi.org/10.1002/humu.21322
Wang, Hong Ying ; Gopalan, Vivek ; Aksentijevich, Ivona ; Yeager, Meredith ; Ma, Chi Adrian ; Ali Mohamoud, Yasmin ; Quinones, Mariam ; Matthews, Casey ; Boland, Joseph ; Niemela, Julie E. ; Torgerson, Troy R. ; Giliani, Silvia ; Uzel, Gulbu ; Orange, Jordan S. ; Shapiro, Ralph ; Notarangelo, Luigi ; Ochs, Hans D. ; Fleisher, Thomas ; Kastner, Daniel ; Chanock, Stephen J. ; Jain, Ashish. / A custom 148 gene-based resequencing chip and the SNP explorer software : New tools to study antibody deficiency. In: Human Mutation. 2010 ; Vol. 31, No. 9. pp. 1080-1088.
@article{b906840df97f4a97bf96c38065d8f60d,
title = "A custom 148 gene-based resequencing chip and the SNP explorer software: New tools to study antibody deficiency",
abstract = "Hyper-IgM syndrome and Common Variable Immunodeficiency are heterogeneous disorders characterized by a predisposition to serious infection and impaired or absent neutralizing antibody responses. Although a number of single gene defects have been associated with these immune deficiency disorders, the genetic basis of many cases is not known. To facilitate mutation screening in patients with these syndromes, we have developed a custom 300-kb resequencing array, the Hyper-IgM/CVID chip, which interrogates 1,576 coding exons and intron-exon junction regions from 148 genes implicated in B-cell development and immunoglobulin isotype switching. Genomic DNAs extracted from patients were hybridized to the array using a high-throughput protocol for target sequence amplification, pooling, and hybridization. A Web-based application, SNP Explorer, was developed to directly analyze and visualize the single nucleotide polymorphism (SNP) annotation and for quality filtering. Several mutations in known disease-susceptibility genes such as CD40LG, TNFRSF13B, IKBKG, AICDA, as well as rare nucleotide changes in other genes such as TRAF3IP2, were identified in patient DNA samples and validated by direct sequencing. We conclude that the Hyper-IgM/CVID chip combined with SNP Explorer may provide a cost-effective tool for high-throughput discovery of novel mutations among hundreds of disease-relevant genes in patients with inherited antibody deficiency.",
keywords = "B cell, CVID, Hyper-IgM, Resequencing microarray, SNP, Somatic hypermutation",
author = "Wang, {Hong Ying} and Vivek Gopalan and Ivona Aksentijevich and Meredith Yeager and Ma, {Chi Adrian} and {Ali Mohamoud}, Yasmin and Mariam Quinones and Casey Matthews and Joseph Boland and Niemela, {Julie E.} and Torgerson, {Troy R.} and Silvia Giliani and Gulbu Uzel and Orange, {Jordan S.} and Ralph Shapiro and Luigi Notarangelo and Ochs, {Hans D.} and Thomas Fleisher and Daniel Kastner and Chanock, {Stephen J.} and Ashish Jain",
year = "2010",
month = "9",
day = "1",
doi = "10.1002/humu.21322",
language = "English",
volume = "31",
pages = "1080--1088",
journal = "Human Mutation",
issn = "1059-7794",
publisher = "Wiley-Liss Inc.",
number = "9",

}

TY - JOUR

T1 - A custom 148 gene-based resequencing chip and the SNP explorer software

T2 - New tools to study antibody deficiency

AU - Wang, Hong Ying

AU - Gopalan, Vivek

AU - Aksentijevich, Ivona

AU - Yeager, Meredith

AU - Ma, Chi Adrian

AU - Ali Mohamoud, Yasmin

AU - Quinones, Mariam

AU - Matthews, Casey

AU - Boland, Joseph

AU - Niemela, Julie E.

AU - Torgerson, Troy R.

AU - Giliani, Silvia

AU - Uzel, Gulbu

AU - Orange, Jordan S.

AU - Shapiro, Ralph

AU - Notarangelo, Luigi

AU - Ochs, Hans D.

AU - Fleisher, Thomas

AU - Kastner, Daniel

AU - Chanock, Stephen J.

AU - Jain, Ashish

PY - 2010/9/1

Y1 - 2010/9/1

N2 - Hyper-IgM syndrome and Common Variable Immunodeficiency are heterogeneous disorders characterized by a predisposition to serious infection and impaired or absent neutralizing antibody responses. Although a number of single gene defects have been associated with these immune deficiency disorders, the genetic basis of many cases is not known. To facilitate mutation screening in patients with these syndromes, we have developed a custom 300-kb resequencing array, the Hyper-IgM/CVID chip, which interrogates 1,576 coding exons and intron-exon junction regions from 148 genes implicated in B-cell development and immunoglobulin isotype switching. Genomic DNAs extracted from patients were hybridized to the array using a high-throughput protocol for target sequence amplification, pooling, and hybridization. A Web-based application, SNP Explorer, was developed to directly analyze and visualize the single nucleotide polymorphism (SNP) annotation and for quality filtering. Several mutations in known disease-susceptibility genes such as CD40LG, TNFRSF13B, IKBKG, AICDA, as well as rare nucleotide changes in other genes such as TRAF3IP2, were identified in patient DNA samples and validated by direct sequencing. We conclude that the Hyper-IgM/CVID chip combined with SNP Explorer may provide a cost-effective tool for high-throughput discovery of novel mutations among hundreds of disease-relevant genes in patients with inherited antibody deficiency.

AB - Hyper-IgM syndrome and Common Variable Immunodeficiency are heterogeneous disorders characterized by a predisposition to serious infection and impaired or absent neutralizing antibody responses. Although a number of single gene defects have been associated with these immune deficiency disorders, the genetic basis of many cases is not known. To facilitate mutation screening in patients with these syndromes, we have developed a custom 300-kb resequencing array, the Hyper-IgM/CVID chip, which interrogates 1,576 coding exons and intron-exon junction regions from 148 genes implicated in B-cell development and immunoglobulin isotype switching. Genomic DNAs extracted from patients were hybridized to the array using a high-throughput protocol for target sequence amplification, pooling, and hybridization. A Web-based application, SNP Explorer, was developed to directly analyze and visualize the single nucleotide polymorphism (SNP) annotation and for quality filtering. Several mutations in known disease-susceptibility genes such as CD40LG, TNFRSF13B, IKBKG, AICDA, as well as rare nucleotide changes in other genes such as TRAF3IP2, were identified in patient DNA samples and validated by direct sequencing. We conclude that the Hyper-IgM/CVID chip combined with SNP Explorer may provide a cost-effective tool for high-throughput discovery of novel mutations among hundreds of disease-relevant genes in patients with inherited antibody deficiency.

KW - B cell

KW - CVID

KW - Hyper-IgM

KW - Resequencing microarray

KW - SNP

KW - Somatic hypermutation

UR - http://www.scopus.com/inward/record.url?scp=77956275991&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77956275991&partnerID=8YFLogxK

U2 - 10.1002/humu.21322

DO - 10.1002/humu.21322

M3 - Article

C2 - 20652909

AN - SCOPUS:77956275991

VL - 31

SP - 1080

EP - 1088

JO - Human Mutation

JF - Human Mutation

SN - 1059-7794

IS - 9

ER -