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The detection of large deletions or duplications in genomic DNA
Author(s) -
Armour J.A.L.,
Barton D.E.,
Cockburn D.J.,
Taylor G.R.
Publication year - 2002
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.10133
Subject(s) - biology , genetics , genotyping , gene dosage , genomic dna , snp genotyping , point mutation , mutation , allele , gene , computational biology , genotype , gene expression
Abstract While methods for the detection of point mutations and small insertions or deletions in genomic DNA are well established, the detection of larger (>100 bp) genomic duplications or deletions can be more difficult. Most mutation scanning methods use PCR as a first step, but the subsequent analyses are usually qualitative rather than quantitative. Gene dosage methods based on PCR need to be quantitative (i.e., they should report molar quantities of starting material) or semi‐quantitative (i.e., they should report gene dosage relative to an internal standard). Without some sort of quantitation, heterozygous deletions and duplications may be overlooked and therefore be under‐ascertained. Gene dosage methods provide the additional benefit of reporting allele drop‐out in the PCR. This could impact on SNP surveys, where large‐scale genotyping may miss null alleles. Here we review recent developments in techniques for the detection of this type of mutation and compare their relative strengths and weaknesses. We emphasize that comprehensive mutation analysis should include scanning for large insertions and deletions and duplications. Hum Mutat 20:325–337, 2002. © 2002 Wiley‐Liss, Inc.