Computerized polymorphic marker identification

Experimental validation and a predicted human polymorphism catalog

John W. Fondon, Gina M. Mele, Ruth I. Brezinschek, Donna Cummings, Ashwini Pande, Jonathan Wren, Kevin M. O'Brien, Kenneth C. Kupfer, Ming Hui Wei, Michael Lerman, John D. Minna, Harold R. Garner

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

A computational system for the prediction of polymorphic loci directly and efficiently from human genomic sequence was developed and verified. A suite of programs, collectively called POMPOUS (polymorphic marker prediction of ubiquitous simple sequences) detects tandem repeats ranging from dinucleotides up to 250 mers, scores them according to predicted level of polymorphism, and designs appropriate flanking primers for PCR amplification. This approach was validated on an approximately 750-kilobase region of human chromosome 3p21.3, involved in lung and breast carcinoma homozygous deletions. Target DNA from 36 paired B lymphoblastoid and lung cancer lines was amplified and allelotyped for 33 loci predicted by POMPOUS to be variable in repeat size. We found that among those 36 predominately Caucasian individuals 22 of the 33 (67%) predicted loci were polymorphic with an average heterozygosity of 0.42. Allele loss in this region was found in 27/36 (75%) of the tumor lines using these markers. POMPOUS provides the genetic researcher with an additional tool for the rapid and efficient identification of polymorphic markers, and through a World Wide Web site, investigators can use POMPOUS to identify polymorphic markers for their research. A catalog of 13,261 potential polymorphic markers and associated primer sets has been created from the analysis of 141,779,504 base pairs of human genomic sequence in GenBank. This data is available on our Web site (pompous.swmed.edu) and will be updated periodically as GenBank is expanded and algorithm accuracy is improved.

Original languageEnglish (US)
Pages (from-to)7514-7519
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume95
Issue number13
DOIs
StatePublished - Jun 23 1998

Fingerprint

Nucleic Acid Databases
Research Personnel
Tandem Repeat Sequences
Human Chromosomes
Base Pairing
Internet
Lung Neoplasms
Alleles
Breast Neoplasms
Polymerase Chain Reaction
Lung
DNA
Research
Neoplasms

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Computerized polymorphic marker identification : Experimental validation and a predicted human polymorphism catalog. / Fondon, John W.; Mele, Gina M.; Brezinschek, Ruth I.; Cummings, Donna; Pande, Ashwini; Wren, Jonathan; O'Brien, Kevin M.; Kupfer, Kenneth C.; Wei, Ming Hui; Lerman, Michael; Minna, John D.; Garner, Harold R.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 95, No. 13, 23.06.1998, p. 7514-7519.

Research output: Contribution to journalArticle

Fondon, JW, Mele, GM, Brezinschek, RI, Cummings, D, Pande, A, Wren, J, O'Brien, KM, Kupfer, KC, Wei, MH, Lerman, M, Minna, JD & Garner, HR 1998, 'Computerized polymorphic marker identification: Experimental validation and a predicted human polymorphism catalog', Proceedings of the National Academy of Sciences of the United States of America, vol. 95, no. 13, pp. 7514-7519. https://doi.org/10.1073/pnas.95.13.7514
Fondon, John W. ; Mele, Gina M. ; Brezinschek, Ruth I. ; Cummings, Donna ; Pande, Ashwini ; Wren, Jonathan ; O'Brien, Kevin M. ; Kupfer, Kenneth C. ; Wei, Ming Hui ; Lerman, Michael ; Minna, John D. ; Garner, Harold R. / Computerized polymorphic marker identification : Experimental validation and a predicted human polymorphism catalog. In: Proceedings of the National Academy of Sciences of the United States of America. 1998 ; Vol. 95, No. 13. pp. 7514-7519.
@article{1e0765e9064e4ebeab6f9a9a09728029,
title = "Computerized polymorphic marker identification: Experimental validation and a predicted human polymorphism catalog",
abstract = "A computational system for the prediction of polymorphic loci directly and efficiently from human genomic sequence was developed and verified. A suite of programs, collectively called POMPOUS (polymorphic marker prediction of ubiquitous simple sequences) detects tandem repeats ranging from dinucleotides up to 250 mers, scores them according to predicted level of polymorphism, and designs appropriate flanking primers for PCR amplification. This approach was validated on an approximately 750-kilobase region of human chromosome 3p21.3, involved in lung and breast carcinoma homozygous deletions. Target DNA from 36 paired B lymphoblastoid and lung cancer lines was amplified and allelotyped for 33 loci predicted by POMPOUS to be variable in repeat size. We found that among those 36 predominately Caucasian individuals 22 of the 33 (67{\%}) predicted loci were polymorphic with an average heterozygosity of 0.42. Allele loss in this region was found in 27/36 (75{\%}) of the tumor lines using these markers. POMPOUS provides the genetic researcher with an additional tool for the rapid and efficient identification of polymorphic markers, and through a World Wide Web site, investigators can use POMPOUS to identify polymorphic markers for their research. A catalog of 13,261 potential polymorphic markers and associated primer sets has been created from the analysis of 141,779,504 base pairs of human genomic sequence in GenBank. This data is available on our Web site (pompous.swmed.edu) and will be updated periodically as GenBank is expanded and algorithm accuracy is improved.",
author = "Fondon, {John W.} and Mele, {Gina M.} and Brezinschek, {Ruth I.} and Donna Cummings and Ashwini Pande and Jonathan Wren and O'Brien, {Kevin M.} and Kupfer, {Kenneth C.} and Wei, {Ming Hui} and Michael Lerman and Minna, {John D.} and Garner, {Harold R.}",
year = "1998",
month = "6",
day = "23",
doi = "10.1073/pnas.95.13.7514",
language = "English (US)",
volume = "95",
pages = "7514--7519",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "13",

}

TY - JOUR

T1 - Computerized polymorphic marker identification

T2 - Experimental validation and a predicted human polymorphism catalog

AU - Fondon, John W.

AU - Mele, Gina M.

AU - Brezinschek, Ruth I.

AU - Cummings, Donna

AU - Pande, Ashwini

AU - Wren, Jonathan

AU - O'Brien, Kevin M.

AU - Kupfer, Kenneth C.

AU - Wei, Ming Hui

AU - Lerman, Michael

AU - Minna, John D.

AU - Garner, Harold R.

PY - 1998/6/23

Y1 - 1998/6/23

N2 - A computational system for the prediction of polymorphic loci directly and efficiently from human genomic sequence was developed and verified. A suite of programs, collectively called POMPOUS (polymorphic marker prediction of ubiquitous simple sequences) detects tandem repeats ranging from dinucleotides up to 250 mers, scores them according to predicted level of polymorphism, and designs appropriate flanking primers for PCR amplification. This approach was validated on an approximately 750-kilobase region of human chromosome 3p21.3, involved in lung and breast carcinoma homozygous deletions. Target DNA from 36 paired B lymphoblastoid and lung cancer lines was amplified and allelotyped for 33 loci predicted by POMPOUS to be variable in repeat size. We found that among those 36 predominately Caucasian individuals 22 of the 33 (67%) predicted loci were polymorphic with an average heterozygosity of 0.42. Allele loss in this region was found in 27/36 (75%) of the tumor lines using these markers. POMPOUS provides the genetic researcher with an additional tool for the rapid and efficient identification of polymorphic markers, and through a World Wide Web site, investigators can use POMPOUS to identify polymorphic markers for their research. A catalog of 13,261 potential polymorphic markers and associated primer sets has been created from the analysis of 141,779,504 base pairs of human genomic sequence in GenBank. This data is available on our Web site (pompous.swmed.edu) and will be updated periodically as GenBank is expanded and algorithm accuracy is improved.

AB - A computational system for the prediction of polymorphic loci directly and efficiently from human genomic sequence was developed and verified. A suite of programs, collectively called POMPOUS (polymorphic marker prediction of ubiquitous simple sequences) detects tandem repeats ranging from dinucleotides up to 250 mers, scores them according to predicted level of polymorphism, and designs appropriate flanking primers for PCR amplification. This approach was validated on an approximately 750-kilobase region of human chromosome 3p21.3, involved in lung and breast carcinoma homozygous deletions. Target DNA from 36 paired B lymphoblastoid and lung cancer lines was amplified and allelotyped for 33 loci predicted by POMPOUS to be variable in repeat size. We found that among those 36 predominately Caucasian individuals 22 of the 33 (67%) predicted loci were polymorphic with an average heterozygosity of 0.42. Allele loss in this region was found in 27/36 (75%) of the tumor lines using these markers. POMPOUS provides the genetic researcher with an additional tool for the rapid and efficient identification of polymorphic markers, and through a World Wide Web site, investigators can use POMPOUS to identify polymorphic markers for their research. A catalog of 13,261 potential polymorphic markers and associated primer sets has been created from the analysis of 141,779,504 base pairs of human genomic sequence in GenBank. This data is available on our Web site (pompous.swmed.edu) and will be updated periodically as GenBank is expanded and algorithm accuracy is improved.

UR - http://www.scopus.com/inward/record.url?scp=13144262863&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=13144262863&partnerID=8YFLogxK

U2 - 10.1073/pnas.95.13.7514

DO - 10.1073/pnas.95.13.7514

M3 - Article

VL - 95

SP - 7514

EP - 7519

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 13

ER -