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    Clinical and molecular characterization of Indian patients with fructose-1, 6-bisphosphatase deficiency: Identification of a frequent variant (E281K).
    Ann Hum Genet 2018 May 18. Epub 2018 May 18.
    Institute of Medical Genetics, Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi, India.
    Fructose-1, 6-bisphosphatase deficiency is an autosomal recessive disorder of gluconeogenesis caused by genetic defect in the FBP1 gene. It is characterized by episodic, often life-threatening metabolic acidosis, liver dysfunction, and hyperlactatemia. Without a high index of suspicion, it may remain undiagnosed with devastating consequences. Read More

    Analysis of type 2 diabetes and obesity genetic variants in Mexican Pima Indians: Marked allelic differentiation among Amerindians at HLA.
    Ann Hum Genet 2018 May 17. Epub 2018 May 17.
    Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ, USA.
    Prevalence of diabetes and obesity in Mexican Pima Indians is low, while prevalence in US Pima Indians is high. Although lifestyle likely accounts for much of the difference, the role of genetic factors is not well explored. To examine this, we genotyped 359 single nucleotide polymorphisms, including established type 2 diabetes and obesity variants from genome-wide association studies (GWAS) and 96 random markers, in 342 Mexican Pimas. Read More

    SLC40A1 and CP single nucleotide polymorphisms in porphyria cutanea tarda patients of mixed ancestry.
    Ann Hum Genet 2018 May 17. Epub 2018 May 17.
    Dermatology Department, Rio de Janeiro State University, Rio de Janeiro, Brazil.
    Porphyria cutanea tarda (PCT) is a multifactorial disease; clinical expression depends on both genetic and acquired factors. Few studies have examined the connection between PCT and the regulation of iron metabolism genes other than the HFE gene. We selected five polymorphisms in the CYBRD1, CP, SLC40A1, and HAMP genes to determine whether these polymorphisms can act as genetic modulators in patients with sporadic PCT. Read More

    Transethnic differences in GWAS signals: A simulation study.
    Ann Hum Genet 2018 May 7. Epub 2018 May 7.
    Department of Medical & Molecular Genetics, King's College London, London, UK.
    Genome-wide association studies (GWASs) have allowed researchers to identify thousands of single nucleotide polymorphisms (SNPs) and other variants associated with particular complex traits. Previous studies have reported differences in the strength and even the direction of GWAS signals across different populations. These differences could be due to a combination of (1) lack of power, (2) allele frequency differences, (3) linkage disequilibrium (LD) differences, and (4) true differences in causal variant effect sizes. Read More

    Calcium-sensing receptor gene polymorphism (rs7652589) is associated with calcium nephrolithiasis in the population of Yi nationality in Southwestern China.
    Ann Hum Genet 2018 Apr 16. Epub 2018 Apr 16.
    Department of Urology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan Province, China.
    The calcium-sensing receptor (CaSR) gene plays an important role in regulating the Ca balance and reducing the risk for calcium stones. In this study, we evaluated the association of CaSR polymorphisms with calcium nephrolithiasis in the population of Yi nationality in Southwestern China. Biochemical variables were evaluated in 624 calcium nephrolithiasis patients and 470 age-matched healthy controls without a history of nephrolithiasis. Read More

    Genome-wide association study of lncRNA polymorphisms with bone mineral density.
    Ann Hum Genet 2018 Apr 16. Epub 2018 Apr 16.
    Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University, Changsha, Hunan, China.
    Recent studies suggested that long noncoding RNAs (lncRNAs) were widely transcribed in the genome, but their potential roles in the genetic complexity of human disorders required further exploration. The purpose of the present study was to explore genetic polymorphisms of lncRNAs associated with bone mineral density (BMD) and its potential value. Based on the lncRNASNP database, 55,906 lncSNPs were selected to conduct a genome-wide association study meta-analysis among 11,140 individuals of seven independent studies for BMDs at femoral neck (FN), lumbar spine, and total hip (HIP). Read More

    Analysis of sports-relevant polymorphisms in a large Brazilian cohort of top-level athletes.
    Ann Hum Genet 2018 Mar 30. Epub 2018 Mar 30.
    Laboratory of Applied Nutrition and Metabolism, School of Physical Education and Sport, University of Sao Paulo, Sao Paulo, SP, Brazil.
    In recent years, there have been an increasing number of genetic variants associated with athletic phenotypes. Here, we selected a set of sports-relevant polymorphisms that have been previously suggested as genetic markers for human physical performance, and we examined their association with athletic status in a large cohort of Brazilians. We evaluated a sample of 1,622 individuals, in which 966 were nonathletes, and 656 were athletes: 328 endurance athletes and 328 power athletes. Read More

    In silico characterization of functional single nucleotide polymorphisms of folate pathway genes.
    Ann Hum Genet 2018 Mar 25. Epub 2018 Mar 25.
    Department of Biotechnology, School of Life Sciences, Manipal University, Planetarium Complex, Manipal, Karnataka, India.
    Folate metabolism genes are pivotal to critical biological processes and are related to several conditions, including developmental, cognitive, and cardiovascular anomalies. A systematic catalog of genetic polymorphisms in protein coding regions, regulatory transcription factor binding sites, and miRNA binding sites associated with folate pathway genes may contribute to personalized medicine. We performed a comprehensive computational survey of single nucleotide polymorphisms (SNPs) of folate pathway genes to highlight functional polymorphisms in the coding region, transcription factor binding sites, and miRNAs binding sites. Read More

    Genetic relatedness of indigenous ethnic groups in northern Borneo to neighboring populations from Southeast Asia, as inferred from genome-wide SNP data.
    Ann Hum Genet 2018 Mar 9. Epub 2018 Mar 9.
    Biotechnology Research Institute, Universiti Malaysia Sabah, Jalan UMS, Sabah, Malaysia.
    The region of northern Borneo is home to the current state of Sabah, Malaysia. It is located closest to the southern Philippine islands and may have served as a viaduct for ancient human migration onto or off of Borneo Island. In this study, five indigenous ethnic groups from Sabah were subjected to genome-wide SNP genotyping. Read More

    Gene-based evaluation of low-frequency variation and genetically-predicted gene expression impacting risk of keloid formation.
    Ann Hum Genet 2018 Feb 27. Epub 2018 Feb 27.
    Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USA.
    Keloids are benign dermal tumors occurring approximately 20 times more often in individuals of African descent as compared to individuals of European descent. While most keloids occur sporadically, a genetic predisposition is supported by both familial aggregation of some keloids and large differences in risk among populations. Despite Africans and African Americans being at increased risk over lighter-skinned individuals, little genetic research exists into this phenotype. Read More

    Association between GOLGB1 tag-polymorphisms and nonsyndromic cleft palate only in the Brazilian population.
    Ann Hum Genet 2018 Feb 12. Epub 2018 Feb 12.
    Department of Oral Diagnosis, School of Dentistry, University of Campinas, Piracicaba, São Paulo, Brazil.
    Nonsyndromic oral clefts are common congenital birth defects that exhibit variable prevalence around the world, often influenced by population-dependent genetic predisposition. Few studies have been performed with nonsyndromic cleft palate only (NSCPO), limiting the knowledge of the genetic risk factors related to this type of oral cleft. Genetic variants in golgin subfamily B member 1 (GOLGB1), a gene that is essential for normal murine palatogenesis, were analyzed in this study to establish its potential association with NSCPO risk in the Brazilian population. Read More

    A novel homozygous missense variant in NECTIN4 (PVRL4) causing ectodermal dysplasia cutaneous syndactyly syndrome.
    Ann Hum Genet 2018 Feb 12. Epub 2018 Feb 12.
    Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
    Ectodermal dysplasia syndactyly syndrome 1 (EDSS1) is a rare form of ectodermal dysplasia including anomalies of hair, nails, and teeth along with bilateral cutaneous syndactyly of hands and feet. In the present report, we performed a clinical and genetic characterization of a consanguineous Pakistani family with four individuals affected by EDSS1. We performed exome sequencing using DNA of one affected individual. Read More

    A novel homozygous variant in BMPR1B underlies acromesomelic dysplasia Hunter-Thompson type.
    Ann Hum Genet 2018 May 10;82(3):129-134. Epub 2018 Jan 10.
    Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
    Acromesomelic dysplasia is genetically heterogeneous group of skeletal disorders characterized by short stature and acromelia and mesomelia of limbs. Acromesomelic dysplasia segregates in an autosomal recessive pattern and is caused by biallelic sequence variants in three genes (NPR2, GDF5, and BMPR1B). A consanguineous family of Pakistani origin segregating a subtype of acromesomelic dysplasia called Hunter-Thompson was clinically and genetically evaluated. Read More

    The rs75932628 and rs2234253 polymorphisms of the TREM2 gene were associated with susceptibility to frontotemporal lobar degeneration in Caucasian populations.
    Ann Hum Genet 2018 Jan 10. Epub 2018 Jan 10.
    Department of Neurology, Tianjin Huanhu Hospital, Tianjin, China.
    Polymorphisms of the triggering receptor expressed on myeloid cells 2 (TREM2) gene have been reported to be potentially associated with the risks of developing frontotemporal lobar degeneration (FTLD), with inconsistent conclusions. This study aims to comprehensively investigate the potential role of TREM2 variants in FTLD risks via a meta-analysis. We included a total of eight eligible articles. Read More

    Increased expression of PRKCB mRNA in peripheral blood mononuclear cells from patients with systemic lupus erythematosus.
    Ann Hum Genet 2018 Jan 3. Epub 2018 Jan 3.
    Department of Dermatology, China-Japan Friendship Hospital, Beijing, China.
    The polymorphism of PRKCB has been proven to be associated with systemic lupus erythematosus (SLE) in our previous study. We aimed to investigate the relationship between expression of PRKCB mRNA and the Disease Activity Index (SLEDAI) and manifestations of SLE. Quantitative reverse transcription polymerase chain reaction (RT-PCR) was applied to examine the expression of PRKCB mRNA in peripheral blood mononuclear cells of 60 patients with SLE and 62 controls. Read More

    p.X654R IDUA variant among Thai individuals with intermediate mucopolysaccharidosis type I and its residual activity as demonstrated in COS-7 cells.
    Ann Hum Genet 2018 May 28;82(3):150-157. Epub 2017 Dec 28.
    Laboratory of Biochemistry, Chulabhorn Research Institute, Bangkok, Thailand.
    Background: Mucopolysaccharidosis type I (MPS I) is a rare autosomal-recessive disorder caused by defects in alpha-L-iduronidase (IDUA), a lysosomal enzyme encoded by the IDUA gene. Herein, we characterized IDUA mutations underlying mucopolysaccharidosis type I intermediate form (Hurler-Scheie syndrome) and its molecular pathogenic mechanisms.

    Methods: Clinical data, activity of the IDUA enzyme in leukocytes, and a mutation of the IDUA gene were analyzed. Read More

    A novel mutation in the HPGD gene causing primary hypertrophic osteoarthropathy with digital clubbing in a Pakistani family.
    Ann Hum Genet 2018 May 28;82(3):171-176. Epub 2017 Dec 28.
    Department of Biotechnology and Genetic Engineering, Kohat University of Science and Technology (KUST), Kohat, Khyber Pakhtunkhwa, Pakistan.
    Primary hypertrophic osteoarthropathy (PHO) is a congenital multisystemic entity characterized by three major clinical symptoms: pachydermia, periostosis, and digital clubbing. Recently it has been reported that pathogenic mutations in two genes are known to be associated with PHO: HPGD and SLCO2A1. In the present study, a five-generation consanguineous Pakistani family harboring primary hypertrophic osteoarthropathy in autosomal-recessive pattern was ascertained. Read More

    The association of RAR-related orphan receptor A (RORA) gene polymorphisms with the risk of asthma.
    Ann Hum Genet 2018 May 28;82(3):158-164. Epub 2017 Dec 28.
    Department of Pediatrics, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China.
    Asthma is a common, heterogeneous chronic respiratory disease characterized by chronic inflammation of the airway, airway hyperreactivity, and airway remodeling. The RAR-related orphan receptor A (RORA) gene has been identified for the pathogenesis of asthma. The purpose of this research was to investigate the relationship between RORA gene polymorphisms and asthma susceptibility in the Chinese Zhuang population. Read More

    A new association between CDK5RAP2 microcephaly and congenital cataracts.
    Ann Hum Genet 2018 May 22;82(3):165-170. Epub 2017 Dec 22.
    Division of Genetics, Department of Pediatrics, King Abdulaziz Medical City, Riyadh, Saudi Arabia.
    Introduction: Primary microcephaly type 3 is a genetically heterogeneous condition caused by a homozygous or compound heterozygous mutation in CDK5 regulatory subunit associated protein 2 (CDK5RAP2) and characterized by reduced head circumference (<5th percentile) with additional phenotypes varying from pigmentary abnormalities to sensorineural hearing loss. Until now, congenital cataracts have not been reported in patients with primary microcephaly type 3.

    Clinical Report: We report multiple affected family members from a consanguineous Saudi family with microcephaly and congenital cataracts. Read More

    Fast permutation tests and related methods, for association between rare variants and binary outcomes.
    Ann Hum Genet 2018 Mar 18;82(2):93-101. Epub 2017 Dec 18.
    Department of Biostatistics, University of Washington, Seattle, WA, USA.
    In large-scale genetic studies, a primary aim is to test for an association between genetic variants and a disease outcome. The variants of interest are often rare and appear with low frequency among subjects. In this situation, statistical tests based on standard asymptotic results do not adequately control the type I error rate, especially if the case : control ratio is unbalanced. Read More

    Expression of miRNA-146a, miRNA-155, IL-2, and TNF-α in inflammatory response to Helicobacter pylori infection associated with cancer progression.
    Ann Hum Genet 2018 May 18;82(3):135-142. Epub 2017 Dec 18.
    Universidade do Sagrado Coração (USC), Bauru, São Paulo, Brazil.
    miRNAs appear to play an important role in controlling the expression of several genes, and they are a potential biomarker and prognostic tool in gastric diseases. We analyzed 53 controls, 86 patients with gastritis, and 19 patients with gastric cancer. Real-time-PCR was used to determine the expression levels of miRNA-146a, miRNA-155, IL-2, and TNF-α. Read More

    The RSPO3 gene as genetic markers for bone mass assessed by quantitative ultrasound in a population of young adults.
    Ann Hum Genet 2018 May 12;82(3):143-149. Epub 2017 Dec 12.
    Faculty of Health Sciences, University of Granada, Granada, Spain.
    Ultrasound bone mass measurement has been postulated as a valuable bone-health assessment tool for primary care. The aim of this study was to analyse the possible relationship between the SPTBN1, RSPO3, CCDC170, DKK1, GPATCH1, and TMEM135 genes, with calcaneal quantitative ultrasound (QUS) in a population of young adults. These genes were first associated with broadband ultrasound attenuation (BUA) in the GEFOS/GENOMOS study. Read More

    Exome sequence analysis and follow up genotyping implicates rare ULK1 variants to be involved in susceptibility to schizophrenia.
    Ann Hum Genet 2018 Mar 17;82(2):88-92. Epub 2017 Nov 17.
    Molecular Psychiatry Laboratory, Division of Psychiatry, University College London, London, UK.
    Schizophrenia (SCZ) is a severe, highly heritable psychiatric disorder. Elucidation of the genetic architecture of the disorder will facilitate greater understanding of the altered underlying neurobiological mechanisms. The aim of this study was to identify likely aetiological variants in subjects affected with SCZ. Read More

    Silenced DMBT1 promotes nasal mucosa epithelial cell growth.
    Ann Hum Genet 2018 Mar 17;82(2):102-108. Epub 2017 Nov 17.
    Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Changzheng Hospital, Shanghai, China.
    Objective: The aim of this study was to investigate the role of the deleted in malignant brain tumors 1 (DMBT1) gene in the development of nasal polyps, as well as related mechanisms.

    Methods: A stable human nasal mucosa epithelial cell (HNEpC) line with low expression of DMBT1 was generated. Three groups were established: a control group (HNEpCs without any treatment), a control short interference RNA (shRNA) group (HNEpCs transfected with an empty vector), and a DMBT1 shRNA group (HNEpCs with silenced DMBT1). Read More

    Recurrence of reported CDH23 mutations causing DFNB12 in a special cohort of South Indian hearing impaired assortative mating families - an evaluation.
    Ann Hum Genet 2018 Mar 17;82(2):119-126. Epub 2017 Nov 17.
    Department of Genetics, Dr. ALM PG Institute of Basic Medical Science, University of Madras, Taramani, Chennai, India.
    Mutations in CDH23 are known to cause autosomal-recessive nonsyndromic hearing loss (DFNB12). Until now, there was only one study describing its frequency in Indian population. We screened for CDH23 mutations to identify prevalent and recurring mutations among South Indian assortative mating hearing-impaired individuals who were identified as non-DFNB1 (GJB2 and GJB6). Read More

    A 3' untranslated region polymorphism rs2304277 in the DNA repair pathway gene OGG1 is a novel risk modulator for urothelial bladder carcinoma.
    Ann Hum Genet 2018 Mar 15;82(2):74-87. Epub 2017 Nov 15.
    Department of Biosciences, COMSATS Institute of Information Technology, Islamabad, Pakistan.
    Altered DNA repair capacity may affect an individual's susceptibility to cancers due to compromised genomic integrity. This study was designed to elucidate the association of selected polymorphisms in DNA repair genes with urothelial bladder carcinoma (UBC). OGG1 rs1052133 and rs2304277, XRCC1 rs1799782 and rs25487, XRCC3 rs861539, XPC rs2228001, and XPD rs13181 were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 200 UBC cases and 200 controls. Read More

    Parent-of-origin-environment interactions in case-parent triads with or without independent controls.
    Ann Hum Genet 2018 Mar 2;82(2):60-73. Epub 2017 Nov 2.
    Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway.
    With case-parent triad data, one can frequently deduce parent of origin of the child's alleles. This allows a parent-of-origin (PoO) effect to be estimated as the ratio of relative risks associated with the alleles inherited from the mother and the father, respectively. A possible cause of PoO effects is DNA methylation, leading to genomic imprinting. Read More

    The MOSAICC study: Assessing feasibility for biological sample collection in epidemiology studies and comparison of DNA yields from saliva and whole blood samples.
    Ann Hum Genet 2018 Mar 27;82(2):114-118. Epub 2017 Oct 27.
    Centre for Public Health, Queen's University Belfast, Belfast, Northern Ireland.
    Biological sample collection is becoming more common in epidemiology research to obtain DNA for genetic analysis. There are many different DNA collection methods but little evidence on their relative effectiveness. Therefore, we took the opportunity of a prospective case-control study in myeloproliferative neoplasms (MPNs) to compare DNA yield from 8. Read More

    Influence of Apolipoprotein E polymorphism on susceptibility of Wilson disease.
    Ann Hum Genet 2018 Mar 23;82(2):53-59. Epub 2017 Oct 23.
    S. N. Pradhan Centre for Neurosciences, University of Calcutta, Kolkata.
    Wilson disease (WD) is an autosomal-recessive disorder caused by mutations in the ATP7B gene leading to abnormal copper deposition in liver and brain. WD manifests diverse neurological and hepatic phenotypes and different age of onset, even among the siblings, with same mutational background suggesting complex nature of the disease and involvement of other candidate genes. In that context, Apolipoprotein E (APOE) and Prion Protein (PRNP) have been proposed to be potential candidates for modifying the WD phenotype and age of onset. Read More

    How many cases of disease in a pedigree imply familial disease?
    Ann Hum Genet 2018 Mar 23;82(2):109-113. Epub 2017 Oct 23.
    Department of Endocrinology & Diabetes, Sir Charles Gairdner Hospital, Nedlands, Australia.
    The ability to perform whole-exome and, increasingly, whole-genome sequencing on large numbers of individuals has led to increased efforts to identify rare genetic variants that affect the risk of both common and rare diseases. In such applications, it is important to identify families that are segregating the rare variants of interest. For rare diseases or rare familial forms of common diseases, pedigrees with multiple affected members are clearly harbouring risk variants. Read More

    Exome Sequencing Identifies a Novel Nonsense Mutation of MYO6 as the Cause of Deafness in a Brazilian Family.
    Ann Hum Genet 2018 Jan 17;82(1):23-34. Epub 2017 Oct 17.
    Laboratório de Otorrinolaringologia/LIM32, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brasil.
    We investigated 313 unrelated subjects who presented with hearing loss to identify the novel genetic causes of this condition in Brazil. Causative GJB2/GJB6 mutations were found in 12.7% of the patients. Read More

    Choledochal Cyst with 17q12 Chromosomal Duplication.
    Ann Hum Genet 2018 Jan 22;82(1):48-51. Epub 2017 Sep 22.
    Department of Pediatrics, Second Faculty of Medicine, Charles University in Prague and University Hospital Motol, Prague, Czech Republic.
    The 17q12 chromosomal region carries the HNF1B gene, mutations of which cause various conditions. When searching for HNF1B/17q12 rearrangements among children with biliary atresia and/or choledochal cysts, we identified a male proband carrying a 17q12 duplication spanning 1698 kb that included 24 genes from TBC1D3C to HNF1B. The boy presented with cholestatic jaundice at the age of 2 weeks due to a choledochal cyst sized 15 ×12 mm (type Ia according to the Todani classification). Read More

    Single-center experience of N-linked Congenital Disorders of Glycosylation with a Summary of Molecularly Characterized Cases in Arabs.
    Ann Hum Genet 2018 Jan 21;82(1):35-47. Epub 2017 Sep 21.
    Centre for Arab Genomic Studies, Dubai, UAE.
    Congenital disorders of glycosylation (CDG) represent an expanding group of conditions that result from defects in protein and lipid glycosylation. Different subgroups of CDG display considerable clinical and genetic heterogeneity due to the highly complex nature of cellular glycosylation. This is further complicated by ethno-geographic differences in the mutational landscape of each of these subgroups. Read More

    Ancestry Informative Marker Panel to Estimate Population Stratification Using Genome-wide Human Array.
    Ann Hum Genet 2017 Nov 11;81(6):225-233. Epub 2017 Sep 11.
    Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, Brazil.
    Case-control studies are a powerful strategy to identify candidate genes in complex diseases. In admixed populations, association studies can be affected by population stratification, leading to spurious genetic associations. Ancestry informative markers (AIMs) can be used to minimise this effect. Read More

    Evaluation of CCAAT/Enhancer Binding Protein (C/EBP) Alpha (CEBPA) and Runt-Related Transcription Factor 1 (RUNX1) Expression in Patients with De Novo Acute Myeloid Leukemia.
    Ann Hum Genet 2017 Nov 11;81(6):276-283. Epub 2017 Sep 11.
    Laboratory Hematology and Blood Bank Department, Faculty of Paramedical, Shahid Beheshti University of Medical Sciences.
    The CCAAT/enhancer binding protein (C/EBP) alpha (CEBPA) and Runt-related transcription factor 1 (RUNX1) genes have been traditionally regarded as two essential genes involved in normal myeloid maturation. Although the link between mutations in these genes and the development of acute myeloid leukemia (AML) has been extensively documented, the ramifications of gene expression dysregulations of CEBPA and RUNX1 has drawn less attention. The present study investigated CEBPA and RUNX1 gene expression levels in 96 primary AML specimens against a normal control group by way of real-time RT-PCR. Read More

    Construction of an Exome-Wide Risk Score for Schizophrenia Based on a Weighted Burden Test.
    Ann Hum Genet 2018 Jan 11;82(1):11-22. Epub 2017 Sep 11.
    UCL Genetics Institute, UCL, Darwin Building, Gower Street, London, WC1E 6BT.
    Polygenic risk scores obtained as a weighted sum of associated variants can be used to explore association in additional data sets and to assign risk scores to individuals. The methods used to derive polygenic risk scores from common SNPs are not suitable for variants detected in whole exome sequencing studies. Rare variants, which may have major effects, are seen too infrequently to judge whether they are associated and may not be shared between training and test subjects. Read More

    Evaluation of a Role for NPY and NPY2R in the Pathogenesis of Obesity by Mutation and Copy Number Variation Analysis in Obese Children and Adolescents.
    Ann Hum Genet 2018 Jan 31;82(1):1-10. Epub 2017 Aug 31.
    Department of Medical Genetics, University of Antwerp, Antwerp, Belgium.
    Neuropeptide Y (NPY) and its G protein-coupled NPY Y2 Receptor (NPY2R) are highly expressed in orexigenic NPY/Agouti-related peptide neurons within the arcuate nucleus, a major integrator of appetite control in the hypothalamus. As NPY and NPY2R are interesting candidate genes for obesity, we hypothesized that a genetic variation in these genes might be implicated in the pathogenesis of obesity. In the first part of this study, we performed a mutation analysis of the coding region of NPY and NPY2R with high-resolution melting curve analysis. Read More

    Interaction Between Val158Met Catechol-O-Methyltransferase Polymorphism and Social Cognitive Functioning in Schizophrenia: Pilot Study.
    Ann Hum Genet 2017 Nov 30;81(6):267-275. Epub 2017 Aug 30.
    Institute of Psychiatry and Neurology, Warsaw, Poland.
    The Val158Met catechol-O-methyltransferase (COMT) functional polymorphism may influence social cognitive functioning in patients with schizophrenia. Aspects of social cognition were evaluated with the Facial Expression Recognition Test, the Voice Emotion Recognition Test, and the Reading the Mind in the Eyes Test. The Short Recognition Memory Test for Faces was used as a control measure. Read More

    Prevalence of Mutations in Deafness-Causing Genes in Cochlear Implanted Patients with Profound Nonsyndromic Sensorineural Hearing Loss in Shandong Province, China.
    Ann Hum Genet 2017 Nov 8;81(6):258-266. Epub 2017 Aug 8.
    Department of Otorhinolaryngology Head and Neck Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Shandong, China.
    The mutations of GJB2, SLC26A4, and mtDNA12SrRNA are the most common inherited causes of nonsyndromic sensorineural hearing loss (NSHL) in China, yet previous genetic screenings were mainly carried on patients with moderate-to-profound impairment. We aimed to detect the mutation frequencies in NSHL population within a more specified range of severity. Patients with profound NSHL who had undergone cochlear implantation in the Shandong Provincial Hospital (Shandong, China) were recruited. Read More

    High Y-chromosomal Differentiation Among Ethnic Groups of Dir and Swat Districts, Pakistan.
    Ann Hum Genet 2017 Nov 3;81(6):234-248. Epub 2017 Aug 3.
    Centre for GeoGenetics, Natural History Museum, University of Copenhagen, Copenhagen, Denmark.
    The ethnic groups that inhabit the mountainous Dir and Swat districts of northern Pakistan are marked by high levels of cultural and phenotypic diversity. To obtain knowledge of the extent of genetic diversity in this region, we investigated Y-chromosomal diversity in five population samples representing the three main ethnic groups residing within these districts, including Gujars, Pashtuns and Kohistanis. A total of 27 Y-chromosomal short tandem repeats (Y-STRs) and 331 Y-chromosomal single nucleotide polymorphisms (Y-SNPs) were investigated. Read More

    The Impact of FOXP3 Polymorphism on the Risk of Allergic Rhinitis: A Meta-Analysis.
    Ann Hum Genet 2017 Nov 25;81(6):284-291. Epub 2017 Jul 25.
    Department of Otolaryngology-Head and Neck Surgery, Tianjin First Center Hospital, Tianjin, People's Republic of China.
    Polymorphisms of several genes were reported to be associated with the risk of allergic rhinitis. Here, we first conducted a meta-analysis to evaluate the potential genetic association between the polymorphisms of the FOXP3 (Forkhead Box P3) gene and the susceptibility to allergic rhinitis. A total of 2671 relevant articles were initially retrieved from the databases of PubMed, Web of Science, Embase, WANFANG/CNKI and Scopus, and six eligible case-control studies were finally enrolled in our meta-analysis, according to our strict inclusion/exclusion criteria. Read More

    Disease-Causing Variants in the ATL1 Gene Are a Rare Cause of Hereditary Spastic Paraplegia among Czech Patients.
    Ann Hum Genet 2017 Nov 23;81(6):249-257. Epub 2017 Jul 23.
    DNA Laboratory, Department of Child Neurology, Charles University 2nd Medical School and University Hospital Motol, Prague, Czech Republic.
    Variants in the ATL1 gene have been repeatedly described as the second most frequent cause of hereditary spastic paraplegia (HSP), a motor neuron disease manifested by progressive lower limb spasticity and weakness. Variants in ATL1 have been described mainly in patients with early onset HSP. We performed Sanger sequencing of all coding exons and adjacent intron regions of the ALT1 gene in 111 Czech patients with pure form of HSP and additional Multiplex-Ligation Probe Analysis (MLPA) testing targeting the ATL1 gene in 56 of them. Read More

    Apolipoprotein E Polymorphism and Left Ventricular Failure in Beta-Thalassemia: A Multivariate Meta-Analysis.
    Ann Hum Genet 2017 Sep 2;81(5):213-223. Epub 2017 Jul 2.
    Department of Computer Science and Biomedical Informatics, University of Thessaly, Papasiopoulou 2-4, Lamia, 35100, Greece.
    Apolipoprotein E (ApoE) is potentially a genetic risk factor for the development of left ventricular failure (LVF), the main cause of death in beta-thalassemia homozygotes. In the present study, we synthesize the results of independent studies examining the effect of ApoE on LVF development in thalassemic patients through a meta-analytic approach. However, all studies report more than one outcome, as patients are classified into three groups according to the severity of the symptoms and the genetic polymorphism. Read More

    Macrophage Migration Inhibitory Factor (MIF) Gene Promotor Polymorphism Is Associated with Increased Fibrosis in Biliary Atresia Patients, but Not with Disease Susceptibility.
    Ann Hum Genet 2017 Sep 28;81(5):177-183. Epub 2017 Jun 28.
    Department of Ophthalmology, The Ohio State University, Columbus, Ohio, USA.
    Two polymorphisms, rs755622 and rs5844572, in the promoter region of the macrophage migration inhibitory factor (MIF) gene influence the basal and/or induced transcriptional activity and have been linked to several inflammatory and autoimmune diseases. The aim of this study was to investigate the association between these two polymorphisms and disease susceptibility in patients with biliary atresia (BA). Allele frequencies of rs755622 and rs5844572 were assessed in 60 Egyptian infants with a confirmed diagnosis of BA. Read More

    Studies on N-Acetyltransferase (NAT2) Genotype Relationships in Emiratis: Confirmation of the Existence of Phenotype Variation among Slow Acetylators.
    Ann Hum Genet 2017 Sep 27;81(5):190-196. Epub 2017 Jun 27.
    Department of Pharmacology, College of Medicine and Health Sciences, UAE University, Al Ain, United Arab Emirates.
    Background And Purpose: Individuals with slow N-acetylation phenotype often experience toxicity from drugs such as isoniazid, sulfonamides, procainamide, and hydralazine, whereas rapid acetylators may not respond to these medications. The highly polymorphic N-acetyltransferase 2 enzyme encoded by the NAT2 gene is one of the N-acetylators in humans with a clear impact on the metabolism of a significant number of important drugs. However, there are limited studies on N-acetylation phenotypes and NAT2 genotypes among Emiratis, and thus this study was carried out to fill this gap. Read More

    Differentiating the Cochran-Armitage Trend Test and Pearson's χ Test: Location and Dispersion.
    Ann Hum Genet 2017 Sep 27;81(5):184-189. Epub 2017 Jun 27.
    McDermott Center of Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, TX, USA.
    In genetic case-control association studies, a standard practice is to perform the Cochran-Armitage (CA) trend test with 1 degree-of-freedom (d.f.) under the assumption of an additive model. Read More

    The Role of TLR4, TNF-α and IL-1β in Type 2 Diabetes Mellitus Development within a North Indian Population.
    Ann Hum Genet 2017 Jul;81(4):141-146
    School of Sport, Exercise and Health Sciences, Loughborough University, Loughborough, UK.
    This study investigated the role of IL-1β-511 (rs16944), TLR4-896 (rs4986790) and TNF-α-308 (rs1800629) polymorphisms in type 2 diabetes mellitus (T2DM) among an endogamous Northern Indian population. Four hundred fourteen participants (204 T2DM patients and 210 nondiabetic controls) were genotyped for IL-1β-511, TLR4-896 and TNF-α-308 loci. The C allele of IL-1β-511 was shown to increase T2DM susceptibility by 75% (OR: 1. Read More

    Detection of Imprinting Effects for Quantitative Traits on X Chromosome Using Nuclear Families with Multiple Daughters.
    Ann Hum Genet 2017 Jul;81(4):147-160
    Department of Statistics and Actuarial Science, The University of Hong Kong, Hong Kong, China.
    Genomic imprinting is an epigenetic phenomenon in which the expression of an allele copy depends on its parental origin. This mechanism has been found to play an important role in many complex diseases. Statistical tests for imprinting effects have been developed for more than 15 years, but they are only suitable for autosomes. Read More

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