Technology challenges in screening single gene disorders

Braun, Andreas; Roth, Richard B.; McGinniss, Matthew J.

doi:10.1007/s00431-003-1343-3

Cited by 11 publications

(9 citation statements)

References 8 publications

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“…SNP genotyping in this sample was carried out with Mass-ARRAY system (Sequenom, San Diego, CA, USA) using matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry (Braun et al 2003) for separation and detection. The entire process has been designed for complete automation including assay design, PCR setup, post-PCR treatment, nanoliter transfer of diagnostic products onto silicon chips, serial reading of chip positions in the mass spectrometer, and final analytical interpretation.…”

Section: Genotypingmentioning

confidence: 99%

Genome-wide association scan for stature in Chinese: evidence for ethnic specific loci

et al. 2008

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In Caucasian, several studies have identified some common variants associated with human stature variation. However, no such study was performed in Chinese, which is the largest population in the world and evidently differs from Caucasian in genetic background. To identify common or ethnic specific genes for stature in Chinese, an initial GWAS and follow-up replication study were performed. Our initial GWAS study found that a group of 13 contiguous SNPs, which span a region of ∼150 kb containing two neighboring genes, zinc finger protein (ZNP) 510 and ZNP782, achieved strong signals for association with stature, with P values ranging from 9.71 × 10 −5 to 3.11 × 10 −6 . After false discovery rate correction for multiple testing, 9 of the 13 SNPs remain significant (FDR q = 0.036-0.046). The follow-up replication study in an independent 2,953 unrelated southern NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptChinese confirmed the association of rs10816533 with stature (P = 0.029). All the13 SNPs were in consistently strong linkage disequilibrium (D′ > 0.99) and formed a single perfect haplotype block. The minor allele frequencies for the 13 contiguous SNPs have evidently ethnic difference, which range from 0.21 to 0.33 in Chinese but have as low as ∼0.017 reported in dbSNP database in Caucasian. The present results suggest that the genomic region containing the ZNP510 and ZNP782 genes is an ethnic specific locus associated with stature variation in Chinese.

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Section: Genotypingmentioning

confidence: 99%

Genome-wide association scan for stature in Chinese: evidence for ethnic specific loci

et al. 2008

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“…[18] Primers were designed using MassARRAY Assay Design 3.1 software. Genotyping quality control procedures leading to SNP exclusion were the following: call rate <90%, MAF <0.05 in the total sample and P <0.001 for deviations from HWE in controls.…”

Section: Methodsmentioning

confidence: 99%

Replication of Caucasian Loci Associated with Osteoporosis-related Traits in East Asians

et al. 2016

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BackgroundMost reported genome-wide association studies (GWAS) seeking to identify the loci of osteoporosis-related traits have involved Caucasian populations. We aimed to identify the single nucleotide polymorphisms (SNPs) of osteoporosis-related traits among East Asian populations from the bone mineral density (BMD)-related loci of an earlier GWAS meta-analysis.MethodsA total of 95 SNPs, identified at the discovery stage of the largest GWAS meta-analysis of BMD, were tested to determine associations with osteoporosis-related traits (BMD, osteoporosis, or fracture) in Korean subjects (n=1,269). The identified SNPs of osteoporosis-related traits in Korean subjects were included in the replication analysis using Chinese (n=2,327) and Japanese (n=768) cohorts.ResultsA total of 17 SNPs were associated with low BMD in Korean subjects. Specifically, 9, 6, 9, and 5 SNPs were associated with the presence of osteoporosis, non-vertebral fractures, vertebral fractures, and any fracture, respectively. Collectively, 35 of the 95 SNPs (36.8%) were associated with one or more osteoporosis-related trait in Korean subjects. Of the 35 SNPs, 19 SNPs (54.3%) were also associated with one or more osteoporosis-related traits in East Asian populations. Twelve SNPs were associated with low BMD in the Chinese and Japanese cohorts. Specifically, 3, 4, and 2 SNPs were associated with the presence of hip fractures, vertebral fractures, and any fracture, respectively.ConclusionsOur results identified the common SNPs of osteoporosis-related traits in both Caucasian and East Asian populations. These SNPs should be further investigated to assess whether they are true genetic markers of osteoporosis.

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“…Genotypes were obtained using MALDI-TOF mass spectrometry on a Sequenom system (Sequenom, Inc., San Diego, CA) with iPLEX assay [27]. Primers were designed using MassARRAY Assay Design 3.1 software.…”

Section: Methodsmentioning

confidence: 99%

Genome-Wide Association Study Identifies ALDH7A1 as a Novel Susceptibility Gene for Osteoporosis

et al. 2010

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Osteoporosis is a major public health problem. It is mainly characterized by low bone mineral density (BMD) and/or low-trauma osteoporotic fractures (OF), both of which have strong genetic determination. The specific genes influencing these phenotypic traits, however, are largely unknown. Using the Affymetrix 500K array set, we performed a case-control genome-wide association study (GWAS) in 700 elderly Chinese Han subjects (350 with hip OF and 350 healthy matched controls). A follow-up replication study was conducted to validate our major GWAS findings in an independent Chinese sample containing 390 cases with hip OF and 516 controls. We found that a SNP, rs13182402 within the ALDH7A1 gene on chromosome 5q31, was strongly associated with OF with evidence combined GWAS and replication studies (P = 2.08×10−9, odds ratio = 2.25). In order to explore the target risk factors and potential mechanism underlying hip OF risk, we further examined this candidate SNP's relevance to hip BMD both in Chinese and Caucasian populations involving 9,962 additional subjects. This SNP was confirmed as consistently associated with hip BMD even across ethnic boundaries, in both Chinese and Caucasians (combined P = 6.39×10−6), further attesting to its potential effect on osteoporosis. ALDH7A1 degrades and detoxifies acetaldehyde, which inhibits osteoblast proliferation and results in decreased bone formation. Our findings may provide new insights into the pathogenesis of osteoporosis.

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Technology challenges in screening single gene disorders

Cited by 11 publications

References 8 publications

Genome-wide association scan for stature in Chinese: evidence for ethnic specific loci

Genome-wide association scan for stature in Chinese: evidence for ethnic specific loci

Replication of Caucasian Loci Associated with Osteoporosis-related Traits in East Asians

Genome-Wide Association Study Identifies ALDH7A1 as a Novel Susceptibility Gene for Osteoporosis

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