462 results match your criteria Human genomics[Journal]


Mutations in ATP13A2 (PARK9) are associated with an amyotrophic lateral sclerosis-like phenotype, implicating this locus in further phenotypic expansion.

Hum Genomics 2019 Apr 16;13(1):19. Epub 2019 Apr 16.

Center for Human Disease Modeling, Duke University Medical Center, Carmichael Building, 300 North Duke Street, Suite 48-118, Durham, NC, 27701, USA.

Background: Amyotrophic lateral sclerosis [1] is a genetically heterogeneous neurodegenerative disorder, characterized by late-onset degeneration of motor neurons leading to progressive limb and bulbar weakness, as well as of the respiratory muscles, which is the primary cause of disease fatality. To date, over 25 genes have been implicated as causative in ALS with C9orf72, SOD1, FUS, and TARDBP accounting for the majority of genetically positive cases.

Results: We identified two patients of Italian and French ancestry with a clinical diagnosis of juvenile-onset ALS who were mutation-negative in any of the known ALS causative genes. Read More

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http://dx.doi.org/10.1186/s40246-019-0203-9DOI Listing

The significance of trisomy 7 mosaicism in noninvasive prenatal screening.

Hum Genomics 2019 Apr 11;13(1):18. Epub 2019 Apr 11.

Prenatal Diagnosis Centre, Guangdong Women and Children Hospital, Guangzhou, 511400, Guangdong, China.

Background: This study was an evaluation of the role of noninvasive prenatal testing (NIPT) in the detection of trisomy 7 in prenatal diagnosis.

Method: A total of 35 consecutive cases underwent screening for trisomies by cell-free DNA testing between April 2015 and November 2017 due to suspicious NIPT results; these cases represented 0.11% of patients (35/31,250) with similar frequencies of abnormal results among the laboratories performing the tests. Read More

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http://dx.doi.org/10.1186/s40246-019-0201-yDOI Listing
April 2019
1 Read

Shared genetic underpinnings of childhood obesity and adult cardiometabolic diseases.

Hum Genomics 2019 Apr 4;13(1):17. Epub 2019 Apr 4.

Laboratorio de Endocrinologia Molecular, Hospital Juárez de México, Mexico City, Mexico.

Background: Obesity during childhood can lead to increased risk of adverse cardiometabolic diseases such as type 2 diabetes and coronary artery disease during adult life. Evidence for strong genetic correlations between child and adult body mass index (BMI) suggest the possibility of shared genetic effects. We performed a test for pleiotropy (shared genetics) and functional enrichment of single nucleotide polymorphisms (SNPs) associated with childhood BMI and 15 adult cardiometabolic traits using a unified statistical approach that integrates pleiotropy and functional annotation data. Read More

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http://dx.doi.org/10.1186/s40246-019-0202-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6449964PMC

Correction to: The evolutionary genetics of lactase persistence in seven ethnic groups across the Iranian plateau.

Hum Genomics 2019 03 22;13(1):16. Epub 2019 Mar 22.

State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223, China.

AbstractIn the original publication of this article [1], the colors of the Fig. 1 are wrong, and are revised in the updated figure below. Read More

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http://dx.doi.org/10.1186/s40246-019-0200-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6429765PMC
March 2019
1 Read

Transcriptome-wide analysis of differentially expressed chemokine receptors, SNPs, and SSRs in the age-related macular degeneration.

Hum Genomics 2019 03 20;13(1):15. Epub 2019 Mar 20.

Mason Eye Institute, University of Missouri, Columbia, MO, 65212, USA.

Background: Age-related macular degeneration (AMD) is the most common, progressive, and polygenic cause of irreversible visual impairment in the world. The molecular pathogenesis of the primary events of AMD is poorly understood. We have investigated a transcriptome-wide analysis of differential gene expression, single-nucleotide polymorphisms (SNPs), indels, and simple sequence repeats (SSRs) in datasets of the human peripheral retina and RPE-choroid-sclera control and AMD. Read More

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http://dx.doi.org/10.1186/s40246-019-0199-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6425613PMC
March 2019
1 Read

Noninvasive prenatal testing for chromosome aneuploidies and subchromosomal microdeletions/microduplications in a cohort of 8141 single pregnancies.

Hum Genomics 2019 03 12;13(1):14. Epub 2019 Mar 12.

Second Affiliated Hospital, Army Military Medical University, Chongqing, 400037, China.

Background: Noninvasive prenatal testing (NIPT) for fetal aneuploidies by scanning cell-free fetal DNA in maternal plasma is rapidly becoming a first-tier aneuploidy screening test in clinical practices. With the development of whole-genome sequencing technology, small subchromosomal deletions and duplications that could not be detected by conventional karyotyping are now able to be detected with NIPT technology.

Methods: In the present study, we examined 8141 single pregnancies with NIPT to calculate the positive predictive values of each of the chromosome aneuploidies and the subchromosomal microdeletions and microduplications. Read More

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http://dx.doi.org/10.1186/s40246-019-0198-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6419401PMC
March 2019
1 Read

vi-HMM: a novel HMM-based method for sequence variant identification in short-read data.

Hum Genomics 2019 02 13;13(1). Epub 2019 Feb 13.

Department of Statistics, Virginia Tech, 250 Drillfield Drive, Blacksburg, 24061, VA, USA.

Background: Accurate and reliable identification of sequence variants, including single nucleotide polymorphisms (SNPs) and insertion-deletion polymorphisms (INDELs), plays a fundamental role in next-generation sequencing (NGS) applications. Existing methods for calling these variants often make simplified assumptions of positional independence and fail to leverage the dependence between genotypes at nearby loci that is caused by linkage disequilibrium (LD).

Results And Conclusion: We propose vi-HMM, a hidden Markov model (HMM)-based method for calling SNPs and INDELs in mapped short-read data. Read More

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http://dx.doi.org/10.1186/s40246-019-0194-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6387560PMC
February 2019
1 Read

Association of HTRA1 and ARMS2 gene polymorphisms with response to intravitreal ranibizumab among neovascular age-related macular degenerative subjects.

Hum Genomics 2019 02 22;13(1):13. Epub 2019 Feb 22.

Department of Surgery, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400, Serdang, Selangor DE, Malaysia.

Background: The association of HTRA1 rs11200638 and ARMS2 rs10490924 gene polymorphisms with response to intravitreal ranibizumab therapy among neovascular AMD (nAMD) subjects in Malaysia was determined in this study, followed by the expression of HTRA1 and ARMS2 genes.

Results: Both single nucleotide polymorphisms (SNPs) recorded a significant association between nAMD and controls with HTRA1 rs11200638 at P = 0.018 (OR = 1. Read More

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https://humgenomics.biomedcentral.com/articles/10.1186/s4024
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http://dx.doi.org/10.1186/s40246-019-0197-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6387522PMC
February 2019
5 Reads

Association of genetic ancestry with colorectal tumor location in Puerto Rican Latinos.

Hum Genomics 2019 02 20;13(1):12. Epub 2019 Feb 20.

Division of Cancer Biology, University of Puerto Rico Comprehensive Cancer Center, PMB 711 Ave. De Diego 89 Ste. 105, San Juan, PR, 00927-6346, USA.

Background: Colorectal cancer (CRC) is the first cause of cancer deaths among Puerto Ricans. The incidence and mortality of CRC in Puerto Rico continue to be on the rise. The burden of CRC in Puerto Rico is higher than among US Hispanics and is second only to African Americans, thus supporting the importance of studying this CRC health disparity. Read More

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http://dx.doi.org/10.1186/s40246-019-0196-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6383234PMC
February 2019
3 Reads

Update on the human and mouse lipocalin (LCN) gene family, including evidence the mouse Mup cluster is result of an "evolutionary bloom".

Hum Genomics 2019 02 19;13(1):11. Epub 2019 Feb 19.

Department of Environmental Health and Center for Environmental Genetics; Department of Pediatrics and Molecular and Developmental Biology, Cincinnati Children's Research Center, University Cincinnati Medical Center, Cincinnati, OH, 45267, USA.

Lipocalins (LCNs) are members of a family of evolutionarily conserved genes present in all kingdoms of life. There are 19 LCN-like genes in the human genome, and 45 Lcn-like genes in the mouse genome, which include 22 major urinary protein (Mup) genes. The Mup genes, plus 29 of 30 Mup-ps pseudogenes, are all located together on chromosome (Chr) 4; evidence points to an "evolutionary bloom" that resulted in this Mup cluster in mouse, syntenic to the human Chr 9q32 locus at which a single MUPP pseudogene is located. Read More

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http://dx.doi.org/10.1186/s40246-019-0191-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6381713PMC
February 2019
2 Reads

Considerations for the use of Cre recombinase for conditional gene deletion in the mouse lens.

Hum Genomics 2019 02 15;13(1):10. Epub 2019 Feb 15.

Department of Biology, Miami University, Oxford, OH, 45056, USA.

Background: Despite a number of different transgenes that can mediate DNA deletion in the developing lens, each has unique features that can make a given transgenic line more or less appropriate for particular studies. The purpose of this work encompasses both a review of transgenes that lead to the expression of Cre recombinase in the lens and a comparative analysis of currently available transgenic lines with a particular emphasis on the Le-Cre and P0-3.9GFPCre lines that can mediate DNA deletion in the lens placode. Read More

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http://dx.doi.org/10.1186/s40246-019-0192-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6377743PMC
February 2019
4 Reads

Toward a clinical diagnostic pipeline for SPINK1 intronic variants.

Hum Genomics 2019 02 12;13(1). Epub 2019 Feb 12.

EFS, Univ Brest, Inserm, UMR 1078, GGB, 29200, Brest, France.

Background: The clinical significance of SPINK1 intronic variants in chronic pancreatitis has been previously assessed by various approaches including a cell culture-based full-length gene assay. A close correlation between the results of this assay and in silico splicing prediction was apparent. However, until now, a clinical diagnostic pipeline specifically designed to classify SPINK1 intronic variants accurately and efficiently has been lacking. Read More

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http://dx.doi.org/10.1186/s40246-019-0193-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6373104PMC
February 2019
11 Reads

The evolutionary genetics of lactase persistence in seven ethnic groups across the Iranian plateau.

Hum Genomics 2019 02 11;13(1). Epub 2019 Feb 11.

State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223, China.

Background: The ability to digest dietary lactose is associated with lactase persistence (LP) in the intestinal lumen in human. The genetic basis of LP has been investigated in many populations in the world. Iran has a long history of pastoralism and the daily consumption of dairy products; thus, we aim to assess how LP has evolved in the Iranian population. Read More

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http://dx.doi.org/10.1186/s40246-019-0195-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6371433PMC
February 2019
1 Read

A genome-wide association study of mitochondrial DNA copy number in two population-based cohorts.

Hum Genomics 2019 01 31;13(1). Epub 2019 Jan 31.

MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.

Background: Mitochondrial DNA copy number (mtDNA CN) exhibits interindividual and intercellular variation, but few genome-wide association studies (GWAS) of directly assayed mtDNA CN exist. We undertook a GWAS of qPCR-assayed mtDNA CN in the Avon Longitudinal Study of Parents and Children (ALSPAC) and the UK Blood Service (UKBS) cohort. After validating and harmonising data, 5461 ALSPAC mothers (16-43 years at mtDNA CN assay) and 1338 UKBS females (17-69 years) were included in a meta-analysis. Read More

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http://dx.doi.org/10.1186/s40246-018-0190-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6357493PMC
January 2019
2 Reads

The association of functional polymorphisms in genes expressed in endothelial cells and smooth muscle cells with the myocardial infarction.

Hum Genomics 2019 01 24;13(1). Epub 2019 Jan 24.

Department of Cardiology, the 2nd Affiliated Hospital of Harbin Medical University, Harbin, 150001, China.

Background: The association of platelet endothelial cell adhesion molecule 1 (PECAM1), hypoxia-inducible factor 1 subunit alpha (HIF1A), and KIAA1462 in myocardial infarction (MI) was investigated. The study included 401 Han Chinese MI patients and 409 controls. Three tag single-nucleotide polymorphisms (SNPs)-PECAM1 rs1867624, HIF1A rs2057482, and KIAA1462 rs3739998-were selected. Read More

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http://dx.doi.org/10.1186/s40246-018-0189-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6345039PMC
January 2019
1 Read

Population and breast cancer patients' analysis reveals the diversity of genomic variation of the BRCA genes in the Mexican population.

Hum Genomics 2019 01 10;13(1). Epub 2019 Jan 10.

Laboratorio de Genómica del Cáncer, Instituto Nacional de Medicina Genómica, Perfiérico Sur, 4809, Arenal Tepepan, 14610, Mexico City, CP, Mexico.

Interpretation of variants of unknown significance (VUS) in genetic tests is complicated in ethnically diverse populations, given the lack of information regarding the common spectrum of genetic variation in clinically relevant genes. Public availability of data obtained from high-throughput genotyping and/or exome massive parallel sequencing (MPS)-based projects from several thousands of outbred samples might become useful tools to evaluate the pathogenicity of a VUS, based on its frequency in different populations. In the case of the Mexican and other Latino populations, several thousands of samples have been genotyped or sequenced during the last few years as part of different efforts to identify common variants associated to common diseases. Read More

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http://dx.doi.org/10.1186/s40246-018-0188-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6327376PMC
January 2019
2 Reads

Germline TP53 and MSH6 mutations implicated in sporadic triple-negative breast cancer (TNBC): a preliminary study.

Hum Genomics 2019 01 10;13(1). Epub 2019 Jan 10.

Department of General Surgery, Nanjing Drum Tower Hospital, Nanjing, Jiangsu Province, China.

Background: Germline BRCA1/2 prevalence is relatively low in sporadic triple-negative breast cancer (TNBC). We hypothesized that non-BRCA genes may also have significant germline contribution to Chinese sporadic TNBC, and the somatic mutational landscape of TNBC may vary between ethnic groups. We therefore conducted this study to investigate germline and somatic mutations in 43 cancer susceptibility genes in Chinese sporadic TNBC. Read More

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https://humgenomics.biomedcentral.com/articles/10.1186/s4024
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http://dx.doi.org/10.1186/s40246-018-0186-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6327518PMC
January 2019
16 Reads

The X chromosome and sex-specific effects in infectious disease susceptibility.

Hum Genomics 2019 01 8;13(1). Epub 2019 Jan 8.

DST-NRF Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.

The X chromosome and X-linked variants have largely been ignored in genome-wide and candidate association studies of infectious diseases due to the complexity of statistical analysis of the X chromosome. This exclusion is significant, since the X chromosome contains a high density of immune-related genes and regulatory elements that are extensively involved in both the innate and adaptive immune responses. Many diseases present with a clear sex bias, and apart from the influence of sex hormones and socioeconomic and behavioural factors, the X chromosome, X-linked genes and X chromosome inactivation mechanisms contribute to this difference. Read More

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https://humgenomics.biomedcentral.com/articles/10.1186/s4024
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http://dx.doi.org/10.1186/s40246-018-0185-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6325731PMC
January 2019
10 Reads

Preimplantation genetic diagnosis and screening (PGD/S) using a semiconductor sequencing platform.

Hum Genomics 2019 01 3;13(1). Epub 2019 Jan 3.

Key Laboratory of Reproductive Genetics, Ministry of Education (Zhejiang University) Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, 310006, China.

Background: Recent advances in semiconductor sequencing platform (SSP) have provided new methods for preimplantation genetic diagnosis/screening (PGD/S). The present study aimed to evaluate the applicability and efficiency of SSP in PGD/S.

Methods: The artificial positive single-cell-like DNAs and normal single-cell samples were chosen to test our semiconductor sequencing platform for preimplantation genetic diagnosis/screening (SSP-PGD/S) method with two widely used whole-genome amplification (WGA) kits. Read More

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http://dx.doi.org/10.1186/s40246-018-0187-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6318931PMC
January 2019
4 Reads

Identification of drug repurposing candidates based on a miRNA-mediated drug and pathway network for cardiac hypertrophy and acute myocardial infarction.

Hum Genomics 2018 12 4;12(1):52. Epub 2018 Dec 4.

Department of Obstetrics, the Second Affiliated Hospital, Harbin Medical University, 246 XueFu Road, Harbin, 150086, Heilongjiang, People's Republic of China.

Background: Cardiac hypertrophy and acute myocardial infarction (AMI) are two common heart diseases worldwide. However, research is needed into the exact pathogenesis and effective treatment strategies for these diseases. Recently, microRNAs (miRNAs) have been suggested to regulate the pathological pathways of heart disease, indicating a potential role in novel treatments. Read More

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http://dx.doi.org/10.1186/s40246-018-0184-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6280539PMC
December 2018
3 Reads

Trans-activation-based risk assessment of BRCA1 BRCT variants with unknown clinical significance.

Hum Genomics 2018 11 20;12(1):51. Epub 2018 Nov 20.

Department of Medical Genetics, Oslo University Hospital, Oslo, Norway.

Background: Deleterious variants in the tumour suppressor BRCA1 are known to cause hereditary breast and ovarian cancer syndrome (HBOC). Missense variants in BRCA1 pose a challenge in clinical care, as their effect on protein functionality often remains unknown. Many of the pathogenic missense variants found in BRCA1 are located in the BRCA1 C-terminal (BRCT) domains, domains that are known to be vital for key functions such as homologous recombination repair, protein-protein interactions and trans-activation (TA). Read More

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http://dx.doi.org/10.1186/s40246-018-0183-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6247502PMC
November 2018
10 Reads

Perceptions of students in health and molecular life sciences regarding pharmacogenomics and personalized medicine.

Hum Genomics 2018 11 14;12(1):50. Epub 2018 Nov 14.

Faculty of Engineering and Natural Sciences, International University of Sarajevo, Hrasnicka cesta 15, 71210 Ilidza, Sarajevo, Bosnia and Herzegovina.

Background: Increasing evidence is demonstrating that a patient's unique genetic profile can be used to detect the disease's onset, prevent its progression, and optimize its treatment. This led to the increased global efforts to implement personalized medicine (PM) and pharmacogenomics (PG) in clinical practice. Here we investigated the perceptions of students from different universities in Bosnia and Herzegovina (BH) towards PG/PM as well as related ethical, legal, and social implications (ELSI). Read More

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https://humgenomics.biomedcentral.com/articles/10.1186/s4024
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http://dx.doi.org/10.1186/s40246-018-0182-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6234656PMC
November 2018
14 Reads

Bayesian variable selection for parametric survival model with applications to cancer omics data.

Hum Genomics 2018 11 6;12(1):49. Epub 2018 Nov 6.

China International Cooperation Center for Environment and Human Health, Nanjing Medical University, 101 Longmian Avenue, Nanjing, 211166, Jiangsu, China.

Background: Modeling thousands of markers simultaneously has been of great interest in testing association between genetic biomarkers and disease or disease-related quantitative traits. Recently, an expectation-maximization (EM) approach to Bayesian variable selection (EMVS) facilitating the Bayesian computation was developed for continuous or binary outcome using a fast EM algorithm. However, it is not suitable to the analyses of time-to-event outcome in many public databases such as The Cancer Genome Atlas (TCGA). Read More

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https://humgenomics.biomedcentral.com/articles/10.1186/s4024
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http://dx.doi.org/10.1186/s40246-018-0179-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6218990PMC
November 2018
12 Reads

Multiple genotype-phenotype association study reveals intronic variant pair on SIDT2 associated with metabolic syndrome in a Korean population.

Hum Genomics 2018 11 1;12(1):48. Epub 2018 Nov 1.

Division of Genome Research, Center for Genome Science, Korea National Institute of Health, Cheongju, Chungcheongbuk-do, 28159, South Korea.

Background: Metabolic syndrome is a risk factor for type 2 diabetes and cardiovascular disease. We identified common genetic variants that alter the risk for metabolic syndrome in the Korean population. To isolate these variants, we conducted a multiple-genotype and multiple-phenotype genome-wide association analysis using the family-based quasi-likelihood score (MFQLS) test. Read More

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http://dx.doi.org/10.1186/s40246-018-0180-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6211397PMC
November 2018
1 Read

Link between short tandem repeats and translation initiation site selection.

Hum Genomics 2018 10 29;12(1):47. Epub 2018 Oct 29.

Iranian Research Center on Aging, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.

Background: Despite their vast biological implication, the relevance of short tandem repeats (STRs)/microsatellites to the protein-coding gene translation initiation sites (TISs) remains largely unknown.

Methods: We performed an Ensembl-based comparative genomics study of all annotated orthologous TIS-flanking sequences in human and 46 other species across vertebrates, on the genomic DNA and cDNA platforms (755,956 TISs), aimed at identifying human-specific STRs in this interval. The collected data were used to examine the hypothesis of a link between STRs and TISs. Read More

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https://humgenomics.biomedcentral.com/articles/10.1186/s4024
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http://dx.doi.org/10.1186/s40246-018-0181-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6206671PMC
October 2018
15 Reads

Identification of gross deletions in FBN1 gene by MLPA.

Hum Genomics 2018 10 4;12(1):46. Epub 2018 Oct 4.

State Key Laboratory of Cardiovascular Disease, Beijing Key Laboratory for Molecular Diagnostics of Cardiovascular Diseases, Diagnostic Laboratory Service, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, China.

Background: Marfan syndrome (MFS) is an autosomal dominant connective tissue disorder caused by mutations in the FBN1 gene. Approximately 90% of classic MFS patients have a FBN1 mutation that can be identified by single-gene sequencing or gene-panel sequencing targeting FBN1. However, a small proportion of MFS patients carry a large genomic deletion in FBN1, which cannot be detected by routine sequencing. Read More

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http://dx.doi.org/10.1186/s40246-018-0178-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6172713PMC
October 2018
2 Reads

Impact of ZBTB7A hypomethylation and expression patterns on treatment response to hydroxyurea.

Hum Genomics 2018 10 1;12(1):45. Epub 2018 Oct 1.

School of Science and Technology, Biology Laboratory, Hellenic Open University, Patras, Greece.

Background: We aimed to clarify the emerging epigenetic landscape in a group of genes classified as "modifier genes" of the β-type globin genes (HBB cluster), known to operate in trans to accomplish the two natural developmental switches in globin expression, from embryonic to fetal during the first trimester of conception and from fetal to adult around the time of birth. The epigenetic alterations were determined in adult sickle cell anemia (SCA) homozygotes and SCA/β-thalassemia compound heterozygotes of Greek origin, who are under hydroxyurea (HU) treatment. Patients were distinguished in HU responders and HU non-responders (those not benefited from the HU) and both, and in vivo and in vitro approaches were implemented. Read More

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https://humgenomics.biomedcentral.com/articles/10.1186/s4024
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http://dx.doi.org/10.1186/s40246-018-0177-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6167880PMC
October 2018
4 Reads

Identification of TBX2 and TBX3 variants in patients with conotruncal heart defects by target sequencing.

Hum Genomics 2018 09 17;12(1):44. Epub 2018 Sep 17.

Department of Pediatric Cardiovascular, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200092, China.

Background: Conotruncal heart defects (CTDs) are heterogeneous congenital heart malformations that result from outflow tract dysplasia; however, the genetic determinants underlying CTDs remain unclear. Increasing evidence demonstrates that dysfunctional TBX2 and TBX3 result in outflow tract malformations, implying that both of them are involved in CTD pathogenesis. We screened for TBX2 and TBX3 variants in a large cohort of CTD patients (n = 588) and population-matched healthy controls (n = 300) by target sequencing and genetically analyzed the expression and function of these variants. Read More

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http://dx.doi.org/10.1186/s40246-018-0176-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6142335PMC
September 2018
1 Read

Architecture of polymorphisms in the human genome reveals functionally important and positively selected variants in immune response and drug transporter genes.

Hum Genomics 2018 09 15;12(1):43. Epub 2018 Sep 15.

NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore, 117456, Singapore.

Background: Genetic polymorphisms can contribute to phenotypic differences amongst individuals, including disease risk and drug response. Characterization of genetic polymorphisms that modulate gene expression and/or protein function may facilitate the identification of the causal variants. Here, we present the architecture of genetic polymorphisms in the human genome focusing on those predicted to be potentially functional/under natural selection and the pathways that they reside. Read More

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http://dx.doi.org/10.1186/s40246-018-0175-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6139121PMC
September 2018
2 Reads

Secondary findings in 421 whole exome-sequenced Chinese children.

Hum Genomics 2018 09 14;12(1):42. Epub 2018 Sep 14.

State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.

Background: Variants with known or possible pathogenicity located in genes that are unrelated to primary disease conditions are defined as secondary findings. Secondary findings are not the primary targets of whole exome and genome sequencing (WES/WGS) assay but can be of great practical value in early disease prevention and intervention. The driving force for this study was to investigate the impact of racial difference and disease background on secondary findings. Read More

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https://humgenomics.biomedcentral.com/articles/10.1186/s4024
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http://dx.doi.org/10.1186/s40246-018-0174-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6137878PMC
September 2018
19 Reads

Linking a role of lncRNAs (long non-coding RNAs) with insulin resistance, accelerated senescence, and inflammation in patients with type 2 diabetes.

Hum Genomics 2018 08 23;12(1):41. Epub 2018 Aug 23.

Department of Cell and Molecular Biology and Dr. Rema Mohan High-Throughput Screening (HTS) Lab, Madras Diabetes Research Foundation and Dr. Mohan's Diabetes Specialties Centre, Gopalapuram, Chennai, 600 086, India.

Background: Studying epigenetics is expected to provide precious information on how environmental factors contribute to type 2 diabetes mellitus (T2DM) at the genomic level. With the progress of the whole-genome resequencing efforts, it is now known that 75-90% of the human genome was transcribed to generate a series of long non-coding RNAs (lncRNAs). While lncRNAs are gaining widespread attention as potential and robust biomarkers in the genesis as well as progression of several disease states, their clinical relevance and regulatory mechanisms are yet to be explored in the field of metabolic disorders including diabetes. Read More

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https://humgenomics.biomedcentral.com/articles/10.1186/s4024
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http://dx.doi.org/10.1186/s40246-018-0173-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6107963PMC
August 2018
21 Reads

Forward and reverse mutations in stages of cancer development.

Hum Genomics 2018 08 22;12(1):40. Epub 2018 Aug 22.

Division of Life Science, Applied Genomics Centre and Centre for Statistical Science, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.

Background: Massive occurrences of interstitial loss of heterozygosity (LOH) likely resulting from gene conversions were found by us in different cancers as a type of single-nucleotide variations (SNVs), comparable in abundance to the commonly investigated gain of heterozygosity (GOH) type of SNVs, raising the question of the relationships between these two opposing types of cancer mutations.

Methods: In the present study, SNVs in 12 tetra sample and 17 trio sample sets from four cancer types along with copy number variations (CNVs) were analyzed by AluScan sequencing, comparing tumor with white blood cells as well as tissues vicinal to the tumor. Four published "nontumor"-tumor metastasis trios and 246 pan-cancer pairs analyzed by whole-genome sequencing (WGS) and 67 trios by whole-exome sequencing (WES) were also examined. Read More

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http://dx.doi.org/10.1186/s40246-018-0170-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6104001PMC
August 2018
11 Reads

The impact of genome-wide association studies on biomedical research publications.

Hum Genomics 2018 08 13;12(1):38. Epub 2018 Aug 13.

Department of Molecular and Cellular Biology, University of Arizona, Tucson, AZ, USA.

The past decade has seen major investment in genome-wide association studies (GWAS). Among the many goals of GWAS, a major one is to identify and motivate research on novel genes involved in complex human disease. To assess whether this goal is being met, we quantified the effect of GWAS on the overall distribution of biomedical research publications and on the subsequent publication history of genes newly associated with complex disease. Read More

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http://dx.doi.org/10.1186/s40246-018-0172-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6090631PMC
August 2018
20 Reads

BRCA1 and BRCA2 mutations and clinical interpretation in 398 ovarian cancer patients: comparison with breast cancer variants in a similar population.

Hum Genomics 2018 08 13;12(1):39. Epub 2018 Aug 13.

Genotipificación y Cáncer Hereditario, Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno" (CEMIC), Galván 4102, C1431FWO, Ciudad Autonoma de Buenos Aires, Argentina.

Background: Ovarian cancer is the leading cause of death worldwide among gynecologic malignancies. The recent approval of inhibitors of poly (ADP-ribose) polymerase (iPARP) in the treatment of ovarian cancer in the presence of a BRCA1/2 mutation has sparked the analysis of women with such diagnosis, which can further benefit from the detection of carriers in the family. Germline sequence and large rearrangements for BRCA1/2 were tested in 398 consecutive epithelial ovarian cancer (EOC) patients. Read More

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http://dx.doi.org/10.1186/s40246-018-0171-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6090818PMC
August 2018
2 Reads

Associations of high-altitude polycythemia with polymorphisms in PIK3CD and COL4A3 in Tibetan populations.

Hum Genomics 2018 07 27;12(1):37. Epub 2018 Jul 27.

Key Laboratory for Molecular Genetic Mechanisms and Intervention Research on High Altitude Disease of Tibet Autonomous Region, School of Medicine, Xizang Minzu University, Xianyang, 712082, Shaanxi, China.

Background: High-altitude polycythemia (HAPC) is a chronic high-altitude disease that can lead to an increase in the production of red blood cells in the people who live in the plateau, a hypoxia environment, for a long time. The most frequent symptoms of HAPC include headache, dizziness, breathlessness, sleep disorders, and dilation of veins. Although chronic hypoxia is the main cause of HAPC, the fundamental pathophysiologic process and related molecular mechanisms responsible for its development remain largely unclear yet. Read More

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http://dx.doi.org/10.1186/s40246-018-0169-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6062892PMC
July 2018
5 Reads

A new bioinformatics tool to help assess the significance of BRCA1 variants.

Hum Genomics 2018 07 11;12(1):36. Epub 2018 Jul 11.

CALIPHO group, SIB Swiss Institute of Bioinformatics, 1211, Geneva 4, Switzerland.

Background: Germline pathogenic variants in the breast cancer type 1 susceptibility gene BRCA1 are associated with a 60% lifetime risk for breast and ovarian cancer. This overall risk estimate is for all BRCA1 variants; obviously, not all variants confer the same risk of developing a disease. In cancer patients, loss of BRCA1 function in tumor tissue has been associated with an increased sensitivity to platinum agents and to poly-(ADP-ribose) polymerase (PARP) inhibitors. Read More

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http://dx.doi.org/10.1186/s40246-018-0168-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6042458PMC
July 2018
1 Read

A novel LRAT mutation affecting splicing in a family with early onset retinitis pigmentosa.

Hum Genomics 2018 07 4;12(1):35. Epub 2018 Jul 4.

Ophthalmic Genetics and Visual Function Branch, National Eye Institute, National Institutes of Health, Bethesda, MD, 20892, USA.

Background And Purpose: Retinitis pigmentosa is an important cause of severe visual dysfunction. This study reports a novel splicing mutation in the lecithin retinol acyltransferase (LRAT) gene associated with early onset retinitis pigmentosa and characterizes the effects of this mutation on mRNA splicing and structure.

Methods: Genome-wide linkage analysis followed by dideoxy sequencing of the linked candidate gene LRAT was performed in a consanguineous Pakistani family with autosomal recessive retinitis pigmentosa. Read More

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http://dx.doi.org/10.1186/s40246-018-0165-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6033202PMC
July 2018
1 Read

Whole-exome sequencing identifies novel pathogenic mutations and putative phenotype-influencing variants in Polish limb-girdle muscular dystrophy patients.

Hum Genomics 2018 07 3;12(1):34. Epub 2018 Jul 3.

Department of Neurodegenerative Disorders, Mossakowski Medical Research Centre, Polish Academy of Sciences, 5 Pawinskiego St., 02-106, Warsaw, Poland.

Background: Limb girdle muscular dystrophies (LGMD) are a group of heterogeneous hereditary myopathies with similar clinical symptoms. Disease onset and progression are highly variable, with an elusive genetic background, and around 50% cases lacking molecular diagnosis.

Methods: Whole exome sequencing (WES) was performed in 73 patients with clinically diagnosed LGMD. Read More

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http://dx.doi.org/10.1186/s40246-018-0167-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6029161PMC
July 2018
4 Reads

Abundance of clinical variants in exons included in multiple transcripts.

Hum Genomics 2018 06 28;12(1):33. Epub 2018 Jun 28.

GeneCology Research Centre, The University of the Sunshine Coast, 90 Sippy Downs Drive, Sippy Downs, Qld, 4556, Australia.

Previous studies showed that the magnitude of selection pressure in constitutive exons is higher than that in alternatively spliced exons. The intensity of selection was also shown to be depended on the inclusion level of exons: the number of transcripts that include an exon. Here, we examined how the difference in selection pressure influences the patterns of clinical variants in human exons. Read More

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http://dx.doi.org/10.1186/s40246-018-0166-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6025840PMC
June 2018
1 Read

Caution needs to be taken when assigning transcription start sites to ends of protein-coding genes: a rebuttal.

Hum Genomics 2018 06 27;12(1):32. Epub 2018 Jun 27.

Department of Biochemistry, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, 31096, Haifa, Israel.

Naturally occurring stress-induced transcriptional readthrough is a recently discovered phenomenon, in which stress conditions lead to dramatic induction of long transcripts as a result of transcription termination failure. In 2015, we reported the induction of such downstream of gene (DoG) containing transcripts upon osmotic stress in human cells, while others observed similar transcripts in virus-infected and cancer cells. Using the rigorous methodology Cap-Seq, we demonstrated that DoGs result from transcriptional readthrough, not de novo initiation. Read More

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http://dx.doi.org/10.1186/s40246-018-0164-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6020437PMC
June 2018
1 Read

The tale of histone modifications and its role in multiple sclerosis.

Hum Genomics 2018 06 22;12(1):31. Epub 2018 Jun 22.

Department of Neurology, 2nd Xiangya Hospital, Central South University, No 139, Renmin Road, Changsha, Hunan Province, China.

Epigenetics defines the persistent modifications of gene expression in a manner that does not involve the corresponding alterations in DNA sequences. It includes modifications of DNA nucleotides, nucleosomal remodeling, and post-translational modifications (PTMs). It is becoming evident that PTMs which act singly or in combination to form "histone codes" orchestrate the chromatin structure and dynamic functions. Read More

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http://dx.doi.org/10.1186/s40246-018-0163-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6013900PMC
June 2018
4 Reads

Computational analysis of mRNA expression profiling in the inner ear reveals candidate transcription factors associated with proliferation, differentiation, and deafness.

Hum Genomics 2018 06 22;12(1):30. Epub 2018 Jun 22.

Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine and Sagol School of Neuroscience, Tel Aviv University, 6997801, Tel Aviv, Israel.

Background: Hearing loss is a major cause of disability worldwide, impairing communication, health, and quality of life. Emerging methods of gene therapy aim to address this morbidity, which can be employed to fix a genetic problem causing hair cell dysfunction and to promote the proliferation of supporting cells in the cochlea and their transdifferentiation into hair cells. In order to extend the applicability of gene therapy, the scientific community is focusing on discovery of additional deafness genes, identifying new genetic variants associated with hearing loss, and revealing new factors that can be manipulated in a coordinated manner to improve hair cell regeneration. Read More

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http://dx.doi.org/10.1186/s40246-018-0161-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6013912PMC
June 2018
2 Reads

Associations between hypertension and the peroxisome proliferator-activated receptor-δ (PPARD) gene rs7770619 C>T polymorphism in a Korean population.

Hum Genomics 2018 06 18;12(1):28. Epub 2018 Jun 18.

Research Center for Silver Science, Institute of Symbiotic Life-TECH, Yonsei University, Seoul, 03722, Korea.

Background: Oxidative stress is associated with the increased risk of hypertension (HTN). This cross-sectional study is aimed to identify the association between the peroxisome proliferator-activated receptor-δ (PPARD) polymorphism and plasma malondialdehyde (MDA), an oxidative stress marker which is related to HTN development, and to determine whether PPARD gene is a candidate gene for HTN.

Results: One thousand seven hundred ninety-three individuals with normal blood pressure (BP) and HTN were included in this cross-sectional study. Read More

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https://humgenomics.biomedcentral.com/articles/10.1186/s4024
Publisher Site
http://dx.doi.org/10.1186/s40246-018-0162-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6006737PMC
June 2018
8 Reads

Oxidative stress-induced chromosome breaks within the ABL gene: a model for chromosome rearrangement in nasopharyngeal carcinoma.

Hum Genomics 2018 06 18;12(1):29. Epub 2018 Jun 18.

Molecular Pathology Unit, Cancer Research Centre, Institute for Medical Research, Kuala Lumpur, Malaysia.

Background: The mechanism underlying chromosome rearrangement in nasopharyngeal carcinoma (NPC) remains elusive. It is known that most of the aetiological factors of NPC trigger oxidative stress. Oxidative stress is a potent apoptotic inducer. Read More

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http://dx.doi.org/10.1186/s40246-018-0160-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6006577PMC
June 2018
7 Reads

Integrating rare genetic variants into pharmacogenetic drug response predictions.

Hum Genomics 2018 05 25;12(1):26. Epub 2018 May 25.

Department of Physiology and Pharmacology, Section of Pharmacogenetics, Karolinska Institutet, SE-171 77, Stockholm, Sweden.

Background: Variability in genes implicated in drug pharmacokinetics or drug response can modulate treatment efficacy or predispose to adverse drug reactions. Besides common genetic polymorphisms, recent sequencing projects revealed a plethora of rare genetic variants in genes encoding proteins involved in drug metabolism, transport, and response.

Results: To understand the global importance of rare pharmacogenetic gene variants, we mapped the variability in 208 pharmacogenes by analyzing exome sequencing data from 60,706 unrelated individuals and estimated the importance of rare and common genetic variants using a computational prediction framework optimized for pharmacogenetic assessments. Read More

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http://dx.doi.org/10.1186/s40246-018-0157-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5968569PMC
May 2018
12 Reads

Mutational analysis of epidermal and hyperproliferative type I keratins in mild and moderate psoriasis vulgaris patients: a possible role in the pathogenesis of psoriasis along with disease severity.

Hum Genomics 2018 05 21;12(1):27. Epub 2018 May 21.

Institute and Department of Dermatology, The First Affiliated Hospital, Anhui Medical University, Hefei, China.

Background: Mutations in keratin proteins have been vastly associated with a wide array of genodermatoses; however, mutations of keratins in psoriasis have not been fully investigated. The main aim of the current research was to identify the mutation in K14, K10, K16, and K17 genes in two stages of psoriasis patients.

Methods: Ninety-six psoriatic skin biopsies were collected. Read More

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http://dx.doi.org/10.1186/s40246-018-0158-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5963134PMC
May 2018
10 Reads

Nonparametric approaches for population structure analysis.

Hum Genomics 2018 05 9;12(1):25. Epub 2018 May 9.

College of Computer and Information Sciences, King Saud University, Riyadh, Saudi Arabia.

The analysis of population structure has many applications in medical and population genetic research. Such analysis is used to provide clear insight into the underlying genetic population substructure and is a crucial prerequisite for any analysis of genetic data. The analysis involves grouping individuals into subpopulations based on shared genetic variations. Read More

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http://dx.doi.org/10.1186/s40246-018-0156-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5944014PMC
May 2018
10 Reads

Better governance, better access: practising responsible data sharing in the METADAC governance infrastructure.

Hum Genomics 2018 04 26;12(1):24. Epub 2018 Apr 26.

Newcastle University, Newcastle upon Tyne, UK.

Background: Genomic and biosocial research data about individuals is rapidly proliferating, bringing the potential for novel opportunities for data integration and use. The scale, pace and novelty of these applications raise a number of urgent sociotechnical, ethical and legal questions, including optimal methods of data storage, management and access. Although the open science movement advocates unfettered access to research data, many of the UK's longitudinal cohort studies operate systems of managed data access, in which access is governed by legal and ethical agreements between stewards of research datasets and researchers wishing to make use of them. Read More

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http://dx.doi.org/10.1186/s40246-018-0154-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5918902PMC
April 2018
14 Reads

Evaluation of a bone morphogenetic protein 6 variant as a cause of iron loading.

Hum Genomics 2018 04 25;12(1):23. Epub 2018 Apr 25.

Institute of Health and Biomedical Innovation and School of Biomedical Sciences, Queensland University of Technology (QUT), 60 Musk Avenue, Kelvin Grove, Brisbane, Queensland, 4059, Australia.

Background: Atypical iron overload without variation in the five clinically associated hereditary hemochromatosis genes is now recognized; however, their etiology remains unknown. Since the identification of iron overload in the bone morphogenetic protein 6 (Bmp6) knockout mouse, the search has been on for clinically pathogenic variants in the BMP6 gene. A recent report proposes that variants in the pro-peptide region of BMP6 are the underlying cause of several cases of iron overload. Read More

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http://dx.doi.org/10.1186/s40246-018-0155-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5918843PMC
April 2018
5 Reads

Tensions in ethics and policy created by National Precision Medicine Programs.

Hum Genomics 2018 04 17;12(1):22. Epub 2018 Apr 17.

Centre for Health, Law and Emerging Technologies (HeLEX), Nuffield Department of Population Health, University of Oxford, Ewert House, Ewert Place, Banbury Road, Oxford, OX2 7DD, UK.

Precision medicine promises to use genomics and other data-intensive approaches to improve diagnosis and develop new treatments for major diseases, but also raises a range of ethical and governance challenges. Implementation of precision medicine in "real world" healthcare systems blurs the boundary between research and care. This has implications for the meaning and validity of consent, and increased potential for discrimination, among other challenges. Read More

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http://dx.doi.org/10.1186/s40246-018-0151-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5904987PMC
April 2018
3 Reads