Comprehensive Arrayed Primer Extension Array for the Detection of 59 Sequence Variants in 15 Conditions Prevalent Among the (Ashkenazi) Jewish Population

Schrijver, Iris; Külm, Maigi; Gardner, Phyllis; Pergament, Eugene; Fiddler, Morris

doi:10.2353/jmoldx.2007.060100

Cited by 19 publications

(12 citation statements)

References 40 publications

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“…Coinciding with the expansion of AJ carrier screening panels has been the continued development and clinical evaluation of multiplexed genotyping platforms [Edelmann et al, 2004; Fares et al, 2008; Kalman et al, 2009; Schrijver et al, 2007; Strom et al, 2004; Strom et al, 2005]. Although the current panel of 16 disorders utilizes commercial assays [Strom et al, 2005; Strom et al, 2006], to facilitate carrier testing of the recently added diseases (E3, USH1F, USH3, HI and NM), we designed a novel multiplexed bead-based assay which simultaneously genotyped their seven mutations and an additional five AJ mutations which cause MSUD and GSDIa.…”

Section: Discussionmentioning

confidence: 99%

Experience with carrier screening and prenatal diagnosis for 16 Ashkenazi Jewish genetic diseases

et al. 2010

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The success of prenatal carrier screening as a disease prevention strategy in the Ashkenazi Jewish (AJ) population has driven the expansion of screening panels as disease-causing founder mutations have been identified. However, the carrier frequencies of many of these mutations have not been reported in large AJ cohorts. We determined the carrier frequencies of over 100 mutations for 16 recessive disorders in the New York metropolitan area AJ population. Among the 100% AJ-descended individuals, screening for 16 disorders resulted in ~1 in 3.3 being a carrier for one disease and ~1 in 24 for two diseases. The carrier frequencies ranged from 0.066 (1 in 15.2; Gaucher disease) to 0.006 (1 in 168; nemaline myopathy), which averaged ~15% higher than those for all screenees. Importantly, over 95% of screenees chose to be screened for all possible AJ diseases, including disorders with lower carrier frequencies and/or detectability. Carrier screening also identified rare individuals homozygous for disease-causing mutations who had previously unrecognized clinical manifestations. Additionally, prenatal testing results and experience for all 16 disorders (n = 574) are reported. Together, these data indicate the general acceptance, carrier frequencies, and prenatal testing results for an expanded panel of 16 diseases in the AJ population.

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Section: Discussionmentioning

confidence: 99%

Experience with carrier screening and prenatal diagnosis for 16 Ashkenazi Jewish genetic diseases

et al. 2010

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“…Eighty-eight SNPs from the β-locus (GenBank: U01317) were used to design a custom SNP-chip in collaboration with Asper Biotechnology (Tartu, Estonia) using arrayed primer extension (APEX) technology [17, 18]. The SNPs summarized in Table 1 were used to perform β-locus SNP genotyping.…”

Section: Methodsmentioning

confidence: 99%

High-density SNP genotyping to define β-globin locus haplotypes

Liu

Muralidhar²,

Singh³

et al. 2009

Blood Cells, Molecules, and Diseases

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Five major β-globin locus haplotypes have been established in individuals with sickle cell disease (SCD) from the Benin, Bantu, Senegal, Cameroon, and Arab-Indian populations. Historically, β-haplotypes were established using restriction fragment length polymorphism (RFLP) analysis across the β-locus, which consists of five functional β-like globin genes located on chromosome 11. Previous attempts to correlate these haplotypes as robust predictors of clinical phenotypes observed in SCD have not been successful. We speculate that the coverage and distribution of the RFLP sites located proximal to or within the globin genes are not sufficiently dense to accurately reflect the complexity of this region. To test our hypothesis, we performed RFLP analysis and high-density single nucleotide polymorphism (SNP) genotyping across the β-locus using DNA samples from either healthy African Americans with normal hemoglobin A (HbAA) or individuals with homozygous SS (HbSS) disease. Using the genotyping data from 88 SNPs and Haploview analysis, we generated a greater number of haplotypes than that observed with RFLP analysis alone. Furthermore, a unique pattern of long-range linkage disequilibrium between the locus control region and the β-like globin genes was observed in the HbSS group. Interestingly, we observed multiple SNPs within the HindIII restriction site located in the Gγ-globin intervening sequence II which produced the same RFLP pattern. These findings illustrated the inability of RFLP analysis to decipher the complexity of sequence variations that impacts genomic structure in this region. Our data suggest that high density SNP mapping may be required to accurately define β-haplotypes that correlate with the different clinical phenotypes observed in SCD.

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“…Methods such as Restriction Fragment Length Polymorphism (RFLP) testing [8] or the Amplification Refractory Mutation System (ARMS) [9], however, are hindered by time-consuming gel-based evaluation of PCR amplicons. Additionally, the platforms that have been developed for high-throughput genotyping purposes, such as a PCR and matrix-assisted, laser desorption/ionization time of flight (MALDI-TOF) mass spectrometry method [10] or arrayed primer extension (APEX) [11], are labor-intensive. Therefore, a more efficient, high-throughput, and automated method of screening for common mutations is needed.…”

Section: Introductionmentioning

confidence: 99%

High-Throughput Carrier Screening Using TaqMan Allelic Discrimination

Fedick

Jalas

et al. 2013

PLoS ONE

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Members of the Ashkenazi Jewish community are at an increased risk for inheritance of numerous genetic diseases such that carrier screening is medically recommended. This paper describes the development and evaluation of 30 TaqMan allelic discrimination qPCR assays for 29 mutations on 2 different high-throughput platforms. Four of these mutations are in the GBA gene and are successfully examined using short amplicons due to the qualitative nature of TaqMan allelic discrimination. Two systems were tested for their reliability (call rate) and consistency with previous diagnoses (diagnostic accuracy) indicating a call rate of 99.04% and a diagnostic accuracy of 100% (+/−0.00%) from one platform, and a call rate of 94.66% and a diagnostic accuracy of 93.35% (+/−0.29%) from a second for 9,216 genotypes. Results for mutations tested at the expected carrier frequency indicated a call rate of 97.87% and a diagnostic accuracy of 99.96% (+/−0.05%). This study demonstrated the ability of a high throughput qPCR methodology to accurately and reliably genotype 29 mutations in parallel. The universally applicable nature of this technology provides an opportunity to increase the number of mutations that can be screened simultaneously, and reduce the cost and turnaround time for accommodating newly identified and clinically relevant mutations.

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Comprehensive Arrayed Primer Extension Array for the Detection of 59 Sequence Variants in 15 Conditions Prevalent Among the (Ashkenazi) Jewish Population

Cited by 19 publications

References 40 publications

Experience with carrier screening and prenatal diagnosis for 16 Ashkenazi Jewish genetic diseases

Experience with carrier screening and prenatal diagnosis for 16 Ashkenazi Jewish genetic diseases

High-density SNP genotyping to define β-globin locus haplotypes

High-Throughput Carrier Screening Using TaqMan Allelic Discrimination

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