Abstract:
BACKGROUND:Recently, increasing innovations improved the accuracy of next generation sequencing (NGS) data. However, the validation of all NGS variants increased the cost and turn-around time of clinical diagnosis, and therefore limited the further development of clinical applications. We aimed to comprehensively assess the necessity of validating NGS variants. METHODS:Validation data of 7,601 NGS variants involving 1,045 genes were collected from 5,190 clinical samples and sequenced by one of five targeted capture panels and two NGS chemistries, respectively. These genes and variants were widely distributed in 24 human chromosomes and mitochondrial genome. Variants validation was firstly processed by Sanger sequencing. If validation results were unavailable or inconsistent with NGS calls, another validation test would be performed by mass spectrometry genotyping. RESULTS:A total of 6,939 high quality NGS variants with ≥35 × depth coverage and ≥35% heterozygous ratio were 100% confirmed by a secondary methodology. 5,775 heterozygous variants were separated from 760 homozygous variants and 404 hemizygous variants by 80% heterozygous ratio. A total of 1.5% (98/6,939) of NGS variants were validated by mass spectrometry genotyping. CONCLUSION:Considering of the above comprehensive assessment, a new variant with high quality from a well-validated capture-based NGS workflow can be reported directly without validation.
journal_name
Mol Genet Genomic Medjournal_title
Molecular genetics & genomic medicineauthors
Zheng J,Zhang H,Banerjee S,Li Y,Zhou J,Yang Q,Tan X,Han P,Fu Q,Cui X,Yuan Y,Zhang M,Shen R,Song H,Zhang X,Zhao L,Peng Z,Wang W,Yin Ydoi
10.1002/mgg3.748subject
Has Abstractpub_date
2019-07-01 00:00:00pages
e00748issue
7issn
2324-9269journal_volume
7pub_type
杂志文章abstract:BACKGROUND:Apolipoprotein E (ApoE) is a glycoprotein that plays an important role in lipid homeostasis at both cerebral and systemic levels. Moreover, the differential distribution of APOE gene alleles among different populations, means that ApoE isoforms could have different effects on lipids metabolism. The present s...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.958
更新日期:2019-11-01 00:00:00
abstract:BACKGROUND:Colon cancer is one of most malignant cancers around worldwide. Nearly 20% patients were diagnosed at colon cancer with metastasis. However, the lack of understanding regarding its pathogenesis brings difficulties to study it. METHODS:In this study, we acquired high-sequence data from GEO dataset, and perfo...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.588
更新日期:2019-04-01 00:00:00
abstract:BACKGROUND:Joubert syndrome (JS, OMIM: 213300) is a recessive developmental disorder characterized by cerebellar vermis hypoplasia and a distinctive mid-hindbrain malformation called the "molar tooth sign" on axial magnetic resonance imaging. To date, more than 35 ciliary genes have been identified as the causative gen...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.1004
更新日期:2019-12-01 00:00:00
abstract::Mutation-induced activation of splice sites in intronic repetitive sequences has contributed significantly to the evolution of exon-intron structure and genetic disease. Such events have been associated with mutations within transposable elements, most frequently in mutation hot-spots of Alus. Here, we report a case o...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.89
更新日期:2014-09-01 00:00:00
abstract::We describe the impact genomics has on the health and readiness of the military service member, highlight several examples of the current and future plans for genomic medicine within the military, discuss challenges to implementation and provide recommendations to address some of those challenges. ...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.335
更新日期:2017-11-01 00:00:00
abstract:BACKGROUND:Sialidosis type 1 is a rare inherited disorder with a high disability. No genetically confirmed mainland Chinese patient with sialidosis type 1 has been reported. This study evaluated the phenotypes and genotypes of mainland Chinese patients with sialidosis type 1. METHODS:It was a retrospective case series...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.1316
更新日期:2020-08-01 00:00:00
abstract:BACKGROUND:Multiple myeloma (MM) is a disease characterized by heterogeneous clinical presentations as well as complex genetic and molecular abnormalities. In MM, cytogenetic analysis is a challenge because of the low proliferation of malignant plasma cells. Thus, interphase fluorescence in situ hybridization (FISH), p...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.1363
更新日期:2020-09-01 00:00:00
abstract:BACKGROUND:Malan syndrome is a recently introduced overgrowth disorder described in a limited number of individuals. Haploinsufficiency and also point mutations of NFIX gene have been proposed as its leading causative mechanism, however, due to the limited number of cases and different deletion sizes, genotype/phenotyp...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章,评审
doi:10.1002/mgg3.997
更新日期:2019-12-01 00:00:00
abstract::Chromosomal microarray analysis (CMA) is now established as the first-tier cytogenetic diagnostic test for fast and accurate detection of chromosomal abnormalities in patients with developmental delay/intellectual disability (DD/ID), multiple congenital anomalies (MCA), and autism spectrum disorders (ASD). We present ...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.57
更新日期:2014-03-01 00:00:00
abstract:BACKGROUND:Alcohol-induced osteonecrosis of femoral head (ONFH) is a complex disease and genetic factors are one of the causes. The purpose of this study is to investigate the effects of RETN (resistin; OMIM: 605565) and LDLR (low density lipoprotein receptor; OMIM: 606945) polymorphisms on the risk of alcohol-induced ...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.822
更新日期:2019-08-01 00:00:00
abstract:BACKGROUND:Copy number variants in coding and noncoding genomic regions have been implicated as risk factor for schizophrenia (SCZ). Rare duplications of the RB1CC1 gene were found enriched in SCZ patients. Considering that the effect of such duplications on RB1CC1 expression has never been evaluated and partial gene d...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.1561
更新日期:2020-12-19 00:00:00
abstract:BACKGROUND:MYO3A, encoding the myosin IIIA protein, is associated with autosomal recessive and autosomal dominant nonsyndromic hearing loss. To date, only two missense variants located in the motor-head domain of MYO3A have been described in autosomal dominant families with progressive, mild-to-profound sensorineural h...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.1343
更新日期:2020-08-01 00:00:00
abstract:BACKGROUND:Truncation FAM83H mutations cause human autosomal dominant hypocalcified amelogenesis imperfecta (ADHCAI), an inherited disorder characterized by severe hardness defects in dental enamel. No enamel defects were observed in Fam83h null mice suggesting that Fam83h truncation mice would better replicate human m...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.724
更新日期:2019-06-01 00:00:00
abstract:BACKGROUND:This study investigated the effects of haplotypes T-G and C-A derived from NG_012836.1:g.4160T>C and NG_012836.1:g.4326G>A on protein expression levels in vitro and identified the functional sequence in the regulatory region of the GABRB3 gene linked to possible associations with schizophrenia. METHODS:Reco...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.652
更新日期:2019-05-01 00:00:00
abstract:BACKGROUND:Historically, groups that are most susceptible to health and healthcare disparities have been underrepresented in medical research. It is imperative to explore approaches that can facilitate the recruitment of underrepresented individuals into research studies. METHODS:Two approaches, hospital and community...
journal_title:Molecular genetics & genomic medicine
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1002/mgg3.443
更新日期:2018-09-01 00:00:00
abstract:BACKGROUND:The prevalence and the role of AGG interruptions within the FMR1 gene in the normal population is unknown. In this study, we investigated the frequent of AGG loss, in one or two alleles within the normal population. The role of AGG in the FMR1 stability has been assessed by correlating AGG loss to the preval...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.946
更新日期:2019-10-01 00:00:00
abstract:BACKGROUND:To explore survival, causes of death, and the prevalence of cardiovascular events in a Norwegian Marfan syndrome (MFS) cohort. MFS is a heritable connective tissue disorder associated with reduced life expectancy-primarily due to aortic pathology. METHODS:A follow-up study of 84 MFS adults, initially invest...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.489
更新日期:2018-11-01 00:00:00
abstract:BACKGROUND:Senior-Loken syndrome is a rare genetic disorder that presents with nephronophthisis and retinal degeneration, leading to end-stage renal disease and progressive blindness. The most frequent cause of juvenile nephronophthisis is a mutation in the nephronophthisis type 1 (NPHP1) gene. NPHP1 encodes the protei...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.1566
更新日期:2020-12-11 00:00:00
abstract:BACKGROUND:Primary microcephaly (MCPH) is a congenital neurodevelopmental disorder manifesting as small brain and intellectual disability. It underlies isolated reduction of the cerebral cortex that is reminiscent of early hominids which makes it suitable model disease to study the hominin-specific volumetric expansion...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.1408
更新日期:2020-09-01 00:00:00
abstract:BACKGROUND:Alport syndrome is a progressive hereditary kidney disease clinically presenting with haematuria, proteinuria, and early onset end-stage renal disease, and often accompanied by hearing loss and ocular abnormalities. The inheritance is X-linked in the majority of families and caused by sequence variants in th...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.1452
更新日期:2020-10-01 00:00:00
abstract:BACKGROUND:Preeclampsia (PE) is a pregnancy-related hypertensive disorder, which may stem from impair placentation. Renin-angiotensin system is one of the mediators of decidualization and trophoblastic proliferation. In the present study women with PE were studied in a comparison of normotensive controls to determine w...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.799
更新日期:2019-07-01 00:00:00
abstract:BACKGROUND:Maple sirup urine disease (MSUD) is an autosomal recessive inherited metabolic disorder. The disease-causing mutations can affect the BCKDHA, BCKDHB, and DBT genes encoding for the E1α, E1β, and E2 subunits of the multienzyme branched-chain α-keto acid dehydrogenase (BCKDH) complex. In the present study, nov...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.1337
更新日期:2020-08-01 00:00:00
abstract:BACKGROUND:It has been proposed that lncRNAs, widely transcribed from genomes, play pivotal regulatory roles in a variety of biological processes, but their function in regulating spermatogenesis in human males is rarely reported. METHODS:QRT-PCR was adopted to detect HOTTIP expression level in testicular tissues from...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.870
更新日期:2019-09-01 00:00:00
abstract:BACKGROUND:Tuberculosis (TB) is a significant worldwide health problem, and is caused by Mycobacteria tuberculosis. Recent studies have suggested that FOXO3 plays vital roles in the risk of immune-related infectious diseases such as TB. METHODS AND RESULTS:The present study aimed to evaluate FOXO3 genetic variants and...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.770
更新日期:2019-08-01 00:00:00
abstract:BACKGROUND:C-Jun and EGFR have not been explored as targets via the mechanism of RNA silencing. Hence, this study designed an efficient C-Jun-h-825 small interfering RNA (siRNA) and investigated its effect on matrix metalloproteinase (MMP) and collagen expression in human keratinocytes exposed to UV radiation. METHODS...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.1047
更新日期:2020-01-01 00:00:00
abstract:BACKGROUND:EAST syndrome is an autosomal recessive disorder caused by loss-of-function mutations in the gene KCNJ10. Among the 14 pathogenic mutations described so far, the p.R65P mutation stands out as the most frequent one and is particularly associated with patients of Pakistani origin. As a result we aimed to estab...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.227
更新日期:2016-06-07 00:00:00
abstract:BACKGROUND:Familial adenomatous polyposis (FAP) is an autosomal dominantly inherited disease which primarily manifested with developing adenomas or polyps in colon or rectum. It is caused by the germline mutations in adenomatous polyposis coli (APC) gene. Patients with FAP are usually manifested with "hundreds or even ...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.505
更新日期:2019-01-01 00:00:00
abstract::The impact of cryptic relatedness (CR) on genomic association studies is well studied and known to inflate false-positive rates as reported by several groups. In contrast, conventional epidemiological studies for environmental risks, the confounding effect of CR is still uninvestigated. In this study, we investigated ...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.4
更新日期:2013-05-01 00:00:00
abstract::Donohue syndrome (DS) is a rare and lethal autosomal recessive disease caused by mutations in the insulin receptor (INSR) gene, manifesting marked insulin resistance, severe growth retardation, hypertrichosis, and characteristic dysmorphic features. We report the clinical, molecular, and biochemical characterization o...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.43
更新日期:2014-01-01 00:00:00
abstract:BACKGROUND:Fanconi anemia (FA) is phenotypically diverse, hereditary condition associated with bone marrow failure, multiple physical abnormalities, and an increased susceptibility to the development of malignancies. Less recognized manifestations of FA include endocrine abnormalities. International discourse has highl...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.1351
更新日期:2020-08-01 00:00:00