title: Comprehensive arrayed primer extension array for the detection of 59 sequence variants in 15 conditions prevalent among the (Ashkenazi) Jewish population.
abstract: In the Ashkenazi Jewish population, serious and lethal genetic conditions occur with relatively high frequency. A single test that encompasses the majority of population-specific mutations is not currently available. For comprehensive carrier screening and molecular diagnostic purposes, we developed a population-specific and inclusive microarray. The arrayed primer extension genotyping microarray carries 59 sequence variant detection sites, of which 53 are detectable bi-directionally. These sites represent the most common variants in Tay-Sachs disease, Bloom syndrome, Canavan disease, Niemann-Pick A, familial dysautonomia, torsion dystonia, mucolipidosis type IV, Fanconi anemia, Gaucher disease, factor XI deficiency, glycogen storage disease type 1a, maple syrup urine disease, nonsyndromic sensorineural hearing loss, familial Mediterranean fever, and glycogen storage disease type III. Several mutations in the selected disorders that are not prevalent per se in the Ashkenazi Jewish populations, as well pseudodeficiency alleles, are also included in the array. The initial technical evaluation of this microarray demonstrates that it is comprehensive, robust, sensitive, specific, and easily modifiable. This cost-effective array is based on a diversely applied platform technology and is suitable for both carrier screening and disease detection in Ashkenazi and Sephardic Jewish populations.
authors: Department of Pathology, L235, Stanford University Medical Center, 300 Pasteur Dr., Stanford, CA 94305, USA. ischrijver@stanfordmed.org
authors: Iris
authors: I
authors: Schrijver
authors: Maigi
authors: M
authors: Külm
authors: Phyllis I
authors: PI
authors: Gardner
authors: Eugene P
authors: EP
authors: Pergament
authors: Morris B
authors: MB
authors: Fiddler
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics; D004265:DNA Helicases / Q000235:genetics; D017931:DNA Primers / Q000235:genetics*; D005820:Genetic Testing / Q000379:methods*; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D007585:Jews / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D011110:Polymorphism, Genetic / Q000235:genetics*; D053484:RecQ Helicases; D035602:Transcriptional Elongation Factors
chemical_list: D002352:Carrier Proteins; D017931:DNA Primers; C114720:Elp1 protein, human; D035602:Transcriptional Elongation Factors; D000251:Adenosine Triphosphatases; C097151:Bloom syndrome protein; D004265:DNA Helicases; D053484:RecQ Helicases