Pitfalls in homozygosity mapping
Pitfalls in homozygosity mapping
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DOI：
10.1016/s0002-9297(07)62966-8
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发表时间：
2000-11-01
影响因子：
9.8
通讯作者：
Wright, AF
中科院分区：
文献类型：
--
作者：
Miano, MG;Jacobson, SG;Wright, AF
在孟德尔和复杂疾病中，使用血统同一性（IBD）方法来定位基因有很大的兴趣。纯合性作图提供了一种快速的方法，通过鉴定合并样本中显示纯合IBD片段的染色体区域，在近亲家庭中定位常染色体隐性基因。在本报告中，我们指出了在增强型S-视锥综合征基因的纯合性定位过程中出现的一些潜在缺陷，这些缺陷是由于：（1）意外的等位基因异质性，使得包含疾病位点的区域由于合并而丢失;（2）鉴定出与疾病位点无关的纯合IBD区域;（3）由于低估了近亲繁殖的程度，LOD分数可能会膨胀，Broman和Weber认为这可能很常见。
There is much interest in use of identity-by-descent (IBD) methods to map genes, both in Mendelian and in complex disorders. Homozygosity mapping provides a rapid means of mapping autosomal recessive genes in consanguineous families by identifying chromosomal regions that show homozygous IBD segments in pooled samples. In this report, we point out some potential pitfalls that arose during the course of homozygosity mapping of the enhanced S-cone syndrome gene, resulting from (1) unexpected allelic heterogeneity, so that the region containing the disease locus was missed as a result of pooling; (2) identification of a homozygous IBD region unrelated to the disease locus; and (3) the potential for inflation of LOD scores as a result of underestimation of the extent of inbreeding, which Broman and Weber suggest may be quite common.