The detection of large deletions or duplications in genomic DNA

被引:103
作者
Armour, JAL
Barton, DE
Cockburn, DJ
Taylor, GR
机构
[1] Univ Nottingham, Queens Med Ctr, Inst Genet, Nottingham NG7 2RD, England
[2] Our Ladys Hosp Sick Children, Natl Ctr Med Genet, Dublin, Ireland
[3] St James Univ Hosp, DNA Lab, Yorkshire Reg Genet Serv, Leeds LS9 7TF, W Yorkshire, England
关键词
gene dosage; gene deletion; gene duplication; DNA array; genetic testing; SNP; mutation detection;
D O I
10.1002/humu.10133
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
While methods for the detection of point mutations and small insertions or deletions in genomic DNA are well established, the detection of larger (> 100 6p) 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.
引用
收藏
页码:325 / 337
页数:13
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