Abstract:
BACKGROUND:Single Nucleotide Polymorphisms (SNPs) identified in Genome Wide Association Studies (GWAS) have generally moderate association with related complex diseases. Accordingly, Multilocus Genetic Risk Scores (MGRSs) have been computed in previous studies in order to assess the cumulative association of multiple SNPs. When several SNPs have to be genotyped for each patient, using successive uniplex pyrosequencing reactions increases analytical reagent expenses and Turnaround Time (TAT). While a set of several pyrosequencing primers could theoretically be used to analyze multiplex amplicons, this would generate overlapping primer-specific pyro-signals that are visually uninterpretable. METHODS:In the current study, two multiplex assays were developed consisting of a quadruplex (n=4) and a quintuplex (n=5) polymerase chain reaction (PCR) each followed by multiplex pyrosequencing analysis. The aim was to reliably but rapidly genotype a set of prostate cancer-related SNPs (n=9). The nucleotide dispensation order was selected using SENATOR software. Multiplex pyro-signals were analyzed using the new AdvISER-MH-PYRO software based on a sparse representation of the signal. Using uniplex assays as gold standard, the concordance between multiplex and uniplex assays was assessed on DNA extracted from patient blood samples (n = 10). RESULTS:All genotypes (n=90) generated with the quadruplex and the quintuplex pyroquencing assays were perfectly (100 %) concordant with uniplex pyrosequencing. Using multiplex genotyping approach for analyzing a set of 90 patients allowed reducing TAT by approximately 75 % (i.e., from 2025 to 470 min) while reducing reagent consumption and cost by approximately 70 % (i.e., from ~229 US$ /patient to ~64 US$ /patient). CONCLUSIONS:This combination of quadruplex and quintuplex pyrosequencing and PCR assays enabled to reduce the amount of DNA required for multi-SNP analysis, and to lower the global TAT and costs of SNP genotyping while providing results as reliable as uniplex analysis. Using this combined multiplex approach also substantially reduced the production of waste material. These genotyping assays appear therefore to be biologically, economically and ecologically highly relevant, being worth to be integrated in genetic-based predictive strategies for better selecting patients at risk for prostate cancer. In addition, the same approach could now equally be transposed to other clinical/research applications relying on the computation of MGRS based on multi-SNP genotyping.
journal_name
BMC Med Genetjournal_title
BMC medical geneticsauthors
Ambroise J,Butoescu V,Robert A,Tombal B,Gala JLdoi
10.1186/s12881-015-0186-xsubject
Has Abstractpub_date
2015-06-25 00:00:00pages
42issn
1471-2350pii
10.1186/s12881-015-0186-xjournal_volume
16pub_type
杂志文章abstract:BACKGROUND:Pendred syndrome is a common autosomal recessive disorder causing deafness. Features include sensorineural hearing impairment, goitre, enlarged vestibular aqueducts (EVA) and occasionally Mondini dysplasia. Hearing impairment and EVA may occur in the absence of goitre or thyroid dyshormonogensis in a conditi...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/1471-2350-14-85
更新日期:2013-08-21 00:00:00
abstract:BACKGROUND:Deep vein thrombosis (DVT) is associated with stroke. Here, we hypothesize that genes associated with DVT may also play roles in the development of stroke. METHODS:we firstly conducted large-scale literature based disease-gene relationship data analysis to explore the genes implicated with DVT and stroke. F...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/s12881-020-01108-9
更新日期:2020-10-22 00:00:00
abstract:BACKGROUND:Autism is a complex, heterogeneous, behaviorally-defined disorder characterized by disruptions of the nervous system and of other systems such as the pituitary-hypothalamic axis. In a previous genome wide screen, we reported linkage of autism with a 1.2 Megabase interval on chromosome 5q31. For the current s...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/1471-2350-8-74
更新日期:2007-12-06 00:00:00
abstract:BACKGROUND:It is believed that hereditary hemochromatosis (HH) might play a role in cardiac disease (heart failure (HF) and ischemia). Mutations within several genes are HH-associated, the most common being the HFE gene. In a large cohort of HF patients, we sought to determine the etiological role and the prognostic si...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/1471-2350-11-117
更新日期:2010-07-29 00:00:00
abstract:BACKGROUND:Hemoglobin A1c (HbA1c) levels diagnose diabetes, predict mortality and are associated with ten single nucleotide polymorphisms (SNPs) in white individuals. Genetic associations in other race groups are not known. We tested the hypotheses that there is race-ethnic variation in 1) HbA1c-associated risk allele ...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/1471-2350-13-30
更新日期:2012-04-27 00:00:00
abstract:BACKGROUND:As cyclin-dependent kinase 5 (CDK5) has been implicated in the abnormal hyperphosphorylation of tau in Alzheimer's disease (AD) brain, and the development of neurofibrillary tangles, we examined the contribution of this gene to the susceptibility for AD. METHODS:We examined genetic variations of CDK5 by gen...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/1471-2350-10-68
更新日期:2009-07-17 00:00:00
abstract:BACKGROUND:Cryptic structural abnormalities within the subtelomeric regions of chromosomes have been the focus of much recent research because of their discovery in a percentage of people with mental retardation (UK terminology: learning disability). These studies focused on subjects (largely children) with various sev...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/1471-2350-5-21
更新日期:2004-08-13 00:00:00
abstract:BACKGROUND:DJ-1 forms part of the neuronal cellular defence mechanism against oxidative insults, due to its ability to undergo self-oxidation. Oxidative stress has been implicated in the pathogenesis of central nervous system damage in different neurodegenerative disorders including Alzheimer's disease and Parkinson's ...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/1471-2350-10-105
更新日期:2009-10-13 00:00:00
abstract:BACKGROUND:CHARGE syndrome is characterized by coloboma, heart defects, choanal atresia, growth retardation, genitourinary malformation and ear abnormalities. The chromodomain helicase DNA-binding protein 7 (CHD7) gene is the major cause of CHARGE syndrome and is inherited in an autosomal dominant manner. Currently, th...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/s12881-019-0813-z
更新日期:2019-05-30 00:00:00
abstract:BACKGROUND:The bladder exstrophy-epispadias complex (BEEC) represents the severe end of the congenital uro-rectal malformation spectrum. Initial studies have implicated rare copy number variations (CNVs), including recurrent duplications of chromosomal region 22q11.21, in BEEC etiology. METHODS:To detect further CNVs,...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/s12881-016-0299-x
更新日期:2016-04-30 00:00:00
abstract:BACKGROUND:Mandibulofacial dysostosis with microcephaly (MFDM) is a rare autosomal dominant genetic disease characterized by intellectual and growth retardations, as well as major microcephaly, induced by missense and splice site variants or microdeletions in the EFTUD2 gene. CASE PRESENTATION:Here, we investigate the...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/s12881-020-01121-y
更新日期:2020-09-17 00:00:00
abstract:BACKGROUND:Two important aspects for the development of anxiety disorders are genetic predisposition and alterations in the hypothalamic-pituitary-adrenal (HPA) axis. In order to identify genetic risk-factors for anxiety, the aim of this exploratory study was to investigate possible relationships between genetic polymo...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/s12881-020-01123-w
更新日期:2020-09-21 00:00:00
abstract:BACKGROUND:Probably the best example of the rise and maintenance of balancing selection as an evolutionary trend is the role of S-haemoglobin (HbS - rs334) in protecting from malaria. Yet, the dynamics of such a process remains poorly understood, particularly in relation to different malaria transmission rates and the ...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/1471-2350-11-21
更新日期:2010-02-03 00:00:00
abstract:BACKGROUND:Insulin like growth factor 2 (IGF2) is an imprinted gene, which has an important role in fetal growth as established in mice models. IGF2 is downregulated through hypomethylation of a differentially methylated region (DMR) in Silver Russell syndrome (SRS), characterised by growth restriction. We have previou...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/1471-2350-13-42
更新日期:2012-05-30 00:00:00
abstract:BACKGROUND:Progressive familial intrahepatic cholestasis (PFIC) type 3 is an autosomal recessive disorder arising from mutations in the ATP-binding cassette subfamily B member 4 (ABCB4) gene. This gene encodes multidrug resistance protein-3 (MDR3) that acts as a hepatocanalicular floppase that transports phosphatidylch...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/s12881-020-01173-0
更新日期:2020-11-30 00:00:00
abstract:BACKGROUND:Published studies present conflicting data regarding the impact of Thrombospondin-1 (TSP-1) expression on prognosis of various cancers. We performed this meta-analysis to illustrate the preliminary predictive value of TSP-1. METHODS:Twenty-four studies with a total of 2379 patients were included. A comprehe...
journal_title:BMC medical genetics
pub_type: 杂志文章,meta分析
doi:10.1186/s12881-020-01073-3
更新日期:2020-06-29 00:00:00
abstract:BACKGROUND:Unique pathogenic mutations in BRCA1 and 2 genes have been reported in different populations of patients originating from the Middle East region. Limited data are available for the Iraqi population. For many reasons a large number of Iraqi patients present to Lebanon for medical care. This is the first repor...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/s12881-019-0885-9
更新日期:2019-09-05 00:00:00
abstract:BACKGROUND:Bilateral posterior periventricular nodular heterotopia PNH is a complex malformation of cortical development with imaging features distinguishing it from classic bilateral PNH associated with filamin (FLNA) mutations. It distinctively consists of variably sized nodules of neurons along the trigones and temp...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/s12881-016-0282-6
更新日期:2016-03-09 00:00:00
abstract:BACKGROUND:CHARGE syndrome is an autosomal dominant disorder, characterized by ocular Coloboma, congenital Heart defects, choanal Atresia, Retardation, Genital anomalies and Ear anomalies. Over 90 % of typical CHARGE patients are mutated in the CHD7 gene, 65 %-70 % of the cases for all typical and suspected cases combi...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/s12881-015-0225-7
更新日期:2015-09-03 00:00:00
abstract:BACKGROUND:Multiple sclerosis (MS) is a complex trait in which alleles at or near the class II loci HLA-DRB1 and HLA-DQB1 contribute significantly to genetic risk. The MHC class II transactivator (MHC2TA) is the master controller of expression of class II genes, and methylation of the promoter of this gene has been pre...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/1471-2350-9-63
更新日期:2008-07-07 00:00:00
abstract:BACKGROUND:To evaluate the promoter methylation status of MUC2 gene and mRNA expression in patients with hepatocellular carcinoma. METHODS:We analyzed MUC2 methylation by MSP, and MUC2 mRNA by real-time PCR in 74 HCC. RESULTS:MUC2 mRNA were lower in HCC tissues (Mean -ΔCt = -4.70) than that in Non-HCC tissues (Mean -...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/1471-2350-14-14
更新日期:2013-01-25 00:00:00
abstract:BACKGROUND:Hereditary non-syndromic hearing loss is the most common inherited sensory defect in humans. The KCNQ4 channel belongs to a family of potassium ion channels that play crucial roles in physiology and disease. Mutations in KCNQ4 underlie deafness non-syndromic autosomal dominant 2, a subtype of autosomal domin...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/s12881-017-0396-5
更新日期:2017-03-24 00:00:00
abstract:BACKGROUND:Adiponectin gene (ADIPOQ) polymorphisms have been shown to affect adiponectin serum concentration and some have been associated with breast cancer (BC) risk. The aims of this study were to describe the frequency of single nucleotide polymorphisms (SNPs) of ADIPOQ in Mexican women with BC and to determine if ...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/s12881-020-01125-8
更新日期:2020-09-25 00:00:00
abstract:BACKGROUND:The TWNK gene encodes the twinkle protein, which is a mitochondrial helicase for DNA replication. The dominant TWNK variants cause progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3, while the recessive variants cause mitochondrial DNA depletion syndrome 7 and Perraul...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/s12881-020-01002-4
更新日期:2020-03-31 00:00:00
abstract:BACKGROUND:The development of next-generation sequencing (NGS) technologies has a great impact in the human variation detection given their high-throughput. These techniques are particularly helpful for the evaluation of the genetic background in disorders of complex genetic etiology such as Hirschsprung disease (HSCR)...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/s12881-015-0235-5
更新日期:2015-10-05 00:00:00
abstract:BACKGROUND:The PALB2 c.2323C>T [p.Q775X] mutation has been reported in at least three breast cancer families and breast cancer cases of French Canadian descent and this has been attributed to common ancestors. The number of mutation-positive cases reported varied based on criteria of ascertainment of index cases tested...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/1471-2350-14-5
更新日期:2013-01-09 00:00:00
abstract:BACKGROUND:Southern China provinces have high incidence of thalassemia, however, sporadic cases can be found in northern China as well. METHODS:People resided in north China who were suspected to have thalassemia were detected mutations by gap-polymerase chain reaction (Gap-PCR) and reverse dot blot (RDB) analyses. Th...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/s12881-019-0818-7
更新日期:2019-05-22 00:00:00
abstract:BACKGROUND:Many epidemiological studies have suggested that insulin-like growth factor1 (IGF1) gene single-nucleotide polymorphisms (SNPs) may be associated with cancer risk. Among several commonly studied polymorphisms in IGF1 gene, rs2195239 and rs2162679 attracted many attentions. So we perform a meta-analysis to de...
journal_title:BMC medical genetics
pub_type: 杂志文章,meta分析
doi:10.1186/s12881-019-0749-3
更新日期:2019-01-17 00:00:00
abstract:BACKGROUND:The results of meta-analyses conducted by previous association studies between total homocysteine and schizophrenia suggest that an elevated total homocysteine level is a risk factor for schizophrenia. However, observational studies have potential limitations, such as confounding and reverse causation. In th...
journal_title:BMC medical genetics
pub_type: 杂志文章,meta分析
doi:10.1186/s12881-015-0197-7
更新日期:2015-07-26 00:00:00
abstract:BACKGROUND:Thalassemia is the most common inherited disease in the world, involving α- or β-globin in red blood cells. Thalassemia cases rank fifth in the list of national catastrophic diseases in Indonesia; however, nationwide screening for thalassemia carriers is not yet mandatory. This study aimed to assess whether ...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/s12881-019-0868-x
更新日期:2019-08-09 00:00:00