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Poor family structure means that it may not be easy, or even feasible, to use ____1____ ___2____ in order to map the underlying gene for certain types of single gene disorders. The disorder may be extremely rare so that insufficient samples can be obtained, or the vast majority of affected individuals are sporadic cases that arise through a ____3____ ___4____ mutation, such as in severe congenital ____5____ disorders. In the past, gene identification in these cases was sometimes possible using cytogenetic analyses to identify a disease-associated chromosome abnormality. Two or more affected individuals might be identified to have a translocation or ____6____ with a common ____7_____ or a recurring interstitial or terminal ____8_____ might be identified. Once the subchromosomal location of the gene had been identified it was possible to use ____9_____ ____10_____ or ____9_____ ___11____ gene approaches to identify the underlying gene. More recently, a more direct approach, ___12____ ____13____ makes it possible to quickly get to the underlying gene without knowing its chromosomal location.

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Poor family structure means that it may not be easy, or even feasible, to use ____1____ ___2____ in order to map the underlying gene for certain types of single gene disorders. The disorder may be extremely rare so that insufficient samples can be obtained, or the vast majority of affected individuals are sporadic cases that arise through a ____3____ ___4____ mutation, such as in severe congenital ____5____ disorders. In the past, gene identification in these cases was sometimes possible using cytogenetic analyses to identify a disease-associated chromosome abnormality. Two or more affected individuals might be identified to have a translocation or ____6____ with a common ____7_____ or a recurring interstitial or terminal ____8_____ might be identified. Once the subchromosomal location of the gene had been identified it was possible to use ____9_____ ____10_____ or ____9_____ ___11____ gene approaches to identify the underlying gene. More recently, a more direct approach, ___12____ ____13____ makes it possible to quickly get to the underlying gene without knowing its chromosomal location.

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