Homozygosity Mapping


The mapping of genes involved in rare recessive disorders in large outbred population is often a difficult task because of the lack of families with multiple affected individuals. Homozygosity mapping is an efficient gene mapping method applicable to rare recessive disorders in inbred populations. Indeed, the method takes advantage of the fact that inbred affected individuals are likely to have two recessive copies of the disease allele from a common ancestor; i.e. two identical‐by‐descent (IBD) alleles. Since small chromosomal regions tend to be transmitted whole, affected individuals will also have identical‐by‐descent alleles at markers located nearby the disease locus and thus will be homozygous at these markers. The basic idea of the method to locate genes involved in rare recessive traits is thus to search for regions of homozygosity that are shared by different affected individuals.

Keywords: gene mapping; inbred populations; DNA pooling; identity‐by‐descent; homozygosity

Figure 1.

Difference between identity‐by‐descent and identity‐by‐state. (a) Son of first‐cousin parents has received two alleles at the disease locus that are the copies of a single allele present in the great‐grandfather. He is autozygous (homozygous with two identical‐by‐descent alleles). (b) Son of two unrelated parents has received two alleles at the disease locus that are of the same type (identical‐by‐state) but not copies of a single allele present in an ancestor (not identical‐by‐descent). The son is homozygous at this locus but not autozygous.

Figure 2.

Schematic illustration of the basic principles of homozygosity mapping. Four inbred patients affected by a same recessive disorder are considered here. Their genome is represented by a straight grey line with markers indicated by small traits. Regions of autozygosity are in black. Because of inbreeding, each patient might have several autozygous regions over the genome. By comparing patients, however, we found that they share a region of autozygosity where the disease locus is likely to map. Patients will all be homozygous at the marker located in this region.



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Génin, Emmanuelle, and Todorov, Alexandre A(Jul 2007) Homozygosity Mapping. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0005407.pub2]