Accounting for genetic heterogeneity in homozygosity mapping: application to Mendelian susceptibility to mycobacterial disease

Mendelian diseases for which a single mutation can be identified in a given patient may be characterized by genetic heterogeneity if different patients bear mutations in several different genes. We demonstrate through simulations that a statistical approach (called S/EmpP) can more easily identify chromosomal regions likely to bear mutations in the context of genetic heterogeneity among consanguineous families compared to standard techniques. Using the S/EmpP approach, we identified two mutations in the genes /IL12RB1/ and /TYK2/ from a sample of consanguineous families with Mendelian susceptibility to Mycobacterial Diseases. The S/EmpP approach can be applied to studies of other Mendelian disorders. (By Audrey Grant, http://jmg.bmj.com/content/early/2011/05/14/jmg.2011.089128.abstract?papetoc )