Gene Identification in Isolated and Inbred Populations

In order to search for non-BRCA1/BRCA2 cancer susceptibility alleles, we are developing appropriate isolated study populations, including a new breast cancer study in Jordan. In addition, I am also exploring the feasibility of identifying existing or newly diagnosed cases from other inbred populations, such as among Bedouin and Druze individuals from Israel. Our new efforts will complement existing resources, such as my continued collaboration with Ken Offit of MSKCC on studies in Ashkenazim, and other study sets already collected, such as consanguineous breast and ovarian cancer cases from Pakistan studied by Steven Narod and colleagues. These efforts aim to maximize our chance of success, particularly for identifying recessive alleles, by controlling the genetic complexity of the populations studied.

One of the existing populations is the Ashkenazi BRCA1/BRCA2-negative, family history positive breast cancer case-unrelated control study from Memorial Sloan-Kettering Cancer Center (MSKCC) headed by Ken Offit and Jeff Boyd. I have applied my likelihood-based homozygosity tract analyses to the initial 101 control individuals genotyped with Affymetrix 500k SNP chips. I have submitted an abstract describing the homozygosity tract mapping methods, which includes analyses of Bedouin DNA samples genotyped on the Affymetrix 500k chip in my lab, showing considerably more homozygosity than either the CEU or Ashkenazi samples.

I have a pilot protocol to study familial breast cancer that concentrates on the Bedouin population in Jordan, a relatively small population with high inbreeding. I am collaborating with Emmanuelle Génin, a statistical geneticist from Francoise Clerget-Darpoux’s group at Institut National de la Santé et de la Recherche Médicale (INSERM), who is an expert in methodological issues related to inbreeding.