Chevre et al., "Positional cloning
of 'Lisch-like', a candidate modifier of susceptibility to type 2 diabetes in mice," PLoS Genetics, vol.
refers to the process in which the gene underlying the disorder is localized and identified in the genome, beginning with comparison of the inheritance of the disease and genetic marker loci in affected families.
Projects focusing on any phase of the gene discovery process, from initial patient ascertainment to positional cloning
, are appropriate.
We have flanking markers for the scs gene but they are not close enough to be used for positional cloning
. Once obtained, closely linked flanking markers will be used to clone and sequence the scs gene.
of a novel potassium channel gene: KVLQT1 mutations cause cardiac arrhythmias.
Linkage mapping, also called positional cloning
, is the process of systematically scanning the entire DNA contents (i.e., the genomes) of various members of families affected by the disorder using regularly spaced, highly variable (i.e., polymorphic) DNA segments whose exact position is known (i.e., genetic markers).
By using complementary strategies of positional cloning
and low-stringency cDNA library screening, two groups identified a novel src-like cytoplasmic tyrosine kinase, named Btk (Bruton agammaglobulinemia tyrosine kinase) as a strong candidate gene for XLA (89,90).
The BRCA1 and BRCA2 genes were discovered by Myriad Genetics using the company's positional cloning
technology, based upon the large proprietary databases of Utah families to which the company has exclusive access.
One technology that has been successfully used to identify disease genes is that of positional cloning
. Positional cloning
refers to the isolation and cloning of a gene after determining its approximate physical location, without prior knowledge of the gene product.
To find the single gene damaged in a mutant fish, most investigators have had to rely upon a laborious strategy called positional cloning
. The first step involves looking for known genetic markers in the DNA of fish with and without the mutation.
Covered methods--adaptable to studying the genetic components of other conditions--include bioinformatics, cytogenetic analyses, mutation screening, microarray analysis, positional cloning
, and recording and mapping of cardiac physiology.
These powerful genomic resources have started to yield the first successful positional cloning
efforts in wheat (Faris et al., 2003; Feuillet et al., 2003; Huang et al., 2003; Yahiaoui et al., 2004; Yan et al., 2003; Yan et al., 2004).