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Mini‐review: Role of the PI3K/Akt pathway and tyrosine phosphatases in Alzheimer's disease susceptibility Ann. Hum. Genet. (IF 1.368) Pub Date : 2020-12-01 David Curtis; Sreejan Bandyopadhyay
A variety of findings from in vitro experiments and animal models support the hypothesis that one contribution to pathogenesis in Alzheimer's disease (AD) is enhanced phosphorylation of tau protein, which may be triggered by amyloid β (Aβ) and mediated by impaired activity of the PI3K/Akt signaling pathway. A number of tyrosine phosphatases act to reduce PI3K/Akt activity, and inhibition of tyrosine
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Identification and functional study of genetic polymorphisms in cyclic nucleotide phosphodiesterase 3A (PDE3A) Ann. Hum. Genet. (IF 1.368) Pub Date : 2020-11-28 You Ran Kim; MyeongJin Yi; Sun‐Ah Cho; Woo‐Young Kim; JungKi Min; Jae‐Gook Shin; Su‐Jun Lee
Phosphodiesterase 3A (PDE3A) is an enzyme that plays an important role in the regulation of cyclic adenosine monophosphate (cAMP)–mediated intracellular signaling in cardiac myocytes and platelets. PDE3A hydrolyzes cAMP, which results in a decrease in intracellular cAMP levels and leads to platelet activation. Whole‐exome sequencing of 50 DNA samples from a healthy Korean population revealed a total
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Isocitrate dehydrogenase 1 gene variants analysis of glioma patients from Pakistan Ann. Hum. Genet. (IF 1.368) Pub Date : 2020-11-23 Huma Naz; Qamar Bashir; Naeem Rashid; Naveed Shahzad
Various somatic isocitrate dehydrogenase 1 (IDH1) gene variants have been reported to drive lower‐grade gliomas and secondary glioblastomas. In the current study, we explored the IDH1 variants in the glioma biopsy samples of patients from Pakistan. We explored the incidence of isocitrate dehydrogenase 1 gene variants by hotspot sequencing in 80 formalin‐fixed paraffin‐embedded tissues of different
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Prenatal diagnosis of Miller–Dieker syndrome by chromosomal microarray Ann. Hum. Genet. (IF 1.368) Pub Date : 2020-10-07 Xiaomei Shi; Weiwei Huang; Jian Lu; Wei He; Qian Liu; Jing Wu
To assess the experience on prenatal diagnosis of Miller–Dieker syndrome (MDS) to further delineate the fetal presentation of this syndrome.
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A role for the MEGF6 gene in predisposition to osteoporosis Ann. Hum. Genet. (IF 1.368) Pub Date : 2020-10-07 Craig C. Teerlink; Michael J. Jurynec; Rolando Hernandez; Jeff Stevens; Dana C. Hughes; Cherie P. Brunker; Kerry Rowe; David J. Grunwald; Julio C. Facelli; Lisa A. Cannon‐Albright
Osteoporosis is a common skeletal disorder characterized by deterioration of bone tissue. The set of genetic factors contributing to osteoporosis is not completely specified. High‐risk osteoporosis pedigrees were analyzed to identify genes that may confer susceptibility to disease. Candidate predisposition variants were identified initially by whole exome sequencing of affected‐relative pairs, approximately
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Differential mutational profiles of familial Mediterranean fever in North Africa. Ann. Hum. Genet. (IF 1.368) Pub Date : 2020-08-20 Djouher Ait-Idir,Bahia Djerdjouri
Familial Mediterranean fever (FMF) is a recessive autoinflammatory disease, mainly occurring in the eastern Mediterranean. In these populations, the five FMF founder mutations are differently distributed. In Algeria, the FMF‐causing variants remain poorly explored. This retrospective study aims to report the mutational profile of Algerian FMF patients and to compare it with North African FMF patients
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The role of WNT1 mutant variant (WNT1c.677C>T ) in osteogenesis imperfecta. Ann. Hum. Genet. (IF 1.368) Pub Date : 2020-08-05 Bashan Zhang,Rong Li,Wenfeng Wang,Xueming Zhou,Beijing Luo,Zinian Zhu,Xibo Zhang,Aijiao Ding
Osteogenesis imperfecta (OI), also known as “brittle bone disease,” is a rare inherited genetic disorder characterized by bone fragility and often associated with short stature. The mutation in WNT1 causes autosomal recessive OI (AR‐OI) due to the key role of WNT/β‐catenin signaling in bone formation. WNT1 mutations cause phenotypes in OI of varying degrees of clinical severity, ranging from moderate
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RT-PCR analysis of mRNA revealed the splice-altering effect of rare intronic variants in monogenic disorders. Ann. Hum. Genet. (IF 1.368) Pub Date : 2020-08-10 Xia Zhang,Wenjuan Qiu,Huili Liu,Xiantao Ye,Yu Sun,Yanjie Fan,Yongguo Yu
Variants perturbing the normal splicing of pre‐mRNA can lead to human diseases. The splice‐altering effect and eventual consequence on gene function was sometimes uncertain and hinders a definitive molecular diagnosis.
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Association of variants in PTPN22, CTLA-4, IL2-RA, and INS genes with type 1 diabetes in Emiratis. Ann. Hum. Genet. (IF 1.368) Pub Date : 2020-09-24 Charu Sharma,Bassam R Ali,Wael Osman,Bachar Afandi,Elhadi H Aburawi,Salem A Beshyah,Zeina Al-Mahayri,Rami H Al-Rifai,Zain Al Yafei,Gehad ElGhazali,Juma Alkaabi
Type 1 diabetes (T1D) is a chronic autoimmune disease with a complex interrelation of genetic and environmental factors. Genetic studies have reported HLA and non‐HLA loci as significant contributors to T1D. However, the genetic basis of T1D among Emiratis is unexplored. This study aims to determine the contribution of four genes PTPN22, CTLA‐4, IL2‐RA, and INS to T1D risk among Emiratis. The association
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Genotyping complex structural variation at the malaria-associated human glycophorin locus using a PCR-based strategy. Ann. Hum. Genet. (IF 1.368) Pub Date : 2020-09-08 Walid Algady,Eleanor Weyell,Daria Mateja,André Garcia,David Courtin,Edward J Hollox
Structural variation in the human genome can affect risk of disease. An example is a complex structural variant of the human glycophorin gene cluster, called DUP4, which is associated with a clinically significant level of protection against severe malaria. The human glycophorin gene cluster harbours at least 23 distinct structural variants, and accurate genotyping of this complex structural variation
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Osteogenesis imperfecta: Novel genetic variants and clinical observations from a clinical exome study of 54 Indian patients. Ann. Hum. Genet. (IF 1.368) Pub Date : 2020-08-07 Vrisha Madhuri,Agnes Selina,Lakshmi Loganathan,Ashis Kumar,Vignesh Kumar,Renita Raymond,Sowmya Ramesh,Nimmy Vincy,Giftson Joel,Deeptiman James,Madhavi Kandagaddala,Antonisamy B
Osteogenesis imperfecta (OI) is a group of inherited disorders with increased bone fragility and wide genetic heterogeneity. We report the outcome of clinical exome sequencing validated by Sanger sequencing in clinically diagnosed 54 OI patients in Indian population. In 52 patients, we report 20 new variants involving both dominant and recessive OI‐specific genes and correlate these with phenotypes
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Detection of mosaicism for segmental and whole chromosome imbalances by targeted sequencing. Ann. Hum. Genet. (IF 1.368) Pub Date : 2020-08-06 Darine Villela,Juliana Sobral de Barros,Silvia Souza da Costa,Talita F M Aguiar,Francine Campagnari,Angela M Vianna-Morgante,Ana C V Krepischi,Carla Rosenberg
Mosaic segmental and whole chromosome copy number alterations are postzygotic variations known to be associated with several disorders. We have previously presented an efficient targeted sequencing approach to simultaneously detect point mutations and copy number variations (CNVs). In this study, we evaluated the efficiency of this approach to detect mosaic CNVs, using seven postnatal and 19 tumor
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Clinical and exome sequencing findings in seven children with Bardet-Biedl syndrome from Turkey. Ann. Hum. Genet. (IF 1.368) Pub Date : 2020-07-20 Evren Gumus,Ebru Tuncez,Ozlem Oz,Merve Saka Guvenc
Bardet–Biedl syndrome (BBS) is a very‐rare autosomal recessive genetic disorder with severe multisystem manifestations. Genetic testing plays an important role in the early diagnosis of the disease. In this study, while trying to elucidate the genetic etiology of seven individuals with clinical BBS diagnosis from six different families, we also aimed to examine the distribution of BBS variations in
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NCAPH is upregulated in endometrial cancer and associated with poor clinicopathologic characteristics. Ann. Hum. Genet. (IF 1.368) Pub Date : 2020-07-06 Xiaofeng Qiu,Zhaoying Gao,Jun Shao,Hong Li
Recently, NCAPH (non‐SMC condensin I complex subunit H), a regulatory subunit of the condensin complex, has captured our attention in various cancer studies. However, the function of NCAPH in endometrial cancer (EC) remains unclear. Our study aims to investigate the role of NCAPH in EC.
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Genomic testing and counseling: The contribution of next-generation sequencing to epilepsy genetics. Ann. Hum. Genet. (IF 1.368) Pub Date : 2020-06-13 Lamia Alsubaie,Taghrid Aloraini,Manal Amoudi,Abdulrahman Swaid,Wafaa Eyiad,Fuad Al Mutairi,Farouq Ababneh,Muhammad Talal Alrifai,Duaa Baarmah,Waleed Altwaijri,Naser Alotaibi,Ashraf Harthi,Ahmad Rumayyan,Ali Alanazi,Mohammad Qrimli,Majid Alfadhel,Ahmed Alfares
Currently, next‐generation sequencing (NGS) technology is more accessible and available to detect the genetic causation of diseases. Though NGS technology benefited some clinical phenotypes, for some clinical diagnoses such as seizures and epileptic disorders, adaptation occurred slowly. The genetic diagnosis was mainly based on epilepsy gene panels and not on whole exome and/or genome sequencing.
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Carrier frequency of CFTR variants in the non-Caucasian populations by genome aggregation database (gnomAD)-based analysis. Ann. Hum. Genet. (IF 1.368) Pub Date : 2020-06-02 Stefania Nappo,Liliana Mannucci,Giuseppe Novelli,Federica Sangiuolo,Maria Rosaria D'Apice,Annalisa Botta
The complexity in the molecular diagnosis of Cystic Fibrosis (CF) also depends on the variable prevalence/incidence of the disease associated with the wide CFTR allelic heterogeneity among different populations. In fact, CF incidence in Asian and African countries is underestimated and the few patients reported so far have rare or unique CFTR pathogenic variants. To obtain insights into CF variants
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Genotype concordance and polygenic risk score estimation across consumer genetic testing data. Ann. Hum. Genet. (IF 1.368) Pub Date : 2020-05-21 Prag Batra,Kuan-Lin Huang
The consumer genomics industry is steadily growing and delivering genetic information to over 10 million individuals. Yet, the implications of using data from different services remain unclear. We investigated the genotyped sites, concordance, and genetic risk estimation using data from three consumer services—two single nucleotide polymorphism (SNP)‐array based and one sequencing based. In an N‐of‐one
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Expanding the phenotype spectrum associated with pathogenic variants in the COL2A1 and COL11A1 genes. Ann. Hum. Genet. (IF 1.368) Pub Date : 2020-05-19 Jana Čopíková,Jana Paděrová,Věra Románková,Markéta Havlovicová,Miroslava Balaščáková,Michaela Zelinová,Šárka Vejvalková,Martina Simandlová,Jana Štěpánková,Věra Hořínová,Eva Kantorová,Gabriela Křečková,Jana Pospíšilová,Arpád Boday,Anna Uhrová Meszarosová,Marek Turnovec,Pavel Votýpka,Petra Lišková,Radka Kremlíková Pourová
We report the clinical findings of 26 individuals from 16 unrelated families carrying variants in the COL2A1 or COL11A1 genes. Using Sanger and next‐generation sequencing, 11 different COL2A1 variants (seven novel), were identified in 13 families (19 affected individuals), all diagnosed with Stickler syndrome (STL) type 1. In nine families, the COL2A1 disease‐causing variant arose de novo. Phenotypically
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MEFV c.2230G>T p.(Ala744Ser) rs61732874 previously misclassified as pathogenic variant due to lack of a population specific database. Ann. Hum. Genet. (IF 1.368) Pub Date : 2020-05-13 Lamia Alsubaie,Randa Alkhalaf,Taghrid Aloraini,Manal Amoudi,Abdulrahman Swaid,Fuad Al Mutairi,Majid Alfadhel,Wafaa Eyaid,Wafaa Sewairi,Ahmed Alfares
Familial Mediterranean fever is a hereditary inflammatory disorder caused by variants in MEFV . c.2230G>T p.(Ala744Ser) rs61732874 is considered to be an established pathogenic variant in MEFV , but in this study we provide a complete evaluation that suggests this variant is likely benign.
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Identification and functional characterization of CYP4V2 genetic variants exhibiting decreased activity of lauric acid metabolism. Ann. Hum. Genet. (IF 1.368) Pub Date : 2020-05-12 Yazun Bashir Jarrar,Jae-Gook Shin,Su-Jun Lee
The objectives of the present study were to identify CYP4V2 genetic variants and characterize their functional consequences. A total of 26CYP4V2 genetic variants were identified, including seven novel variants in 60 randomly selected healthy subjects. Six protein‐coding variants were studied, including three novel variants (L22V, R287T, and G410C) and three previously reported variants (R36S, Q259K
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Lack of association between the GNB3 rs5443, HIF1A rs11549465 polymorphisms, physiological and functional characteristics. Ann. Hum. Genet. (IF 1.368) Pub Date : 2020-05-11 Edit Bosnyák,Emese Trájer,Gabriella Alszászi,Ákos Móra,István Györe,Anna Udvardy,Miklós Tóth,Márta Szmodis
The aim was to examine the association between the hypoxia‐inducible factor‐1α (HIF1A) gene and the guanine nucleotide binding protein beta polypeptide 3 (GNB3) gene polymorphisms and the endurance/power athlete status and relative aerobic capacity. Another goal of this study was to reveal the connection between GNB3, blood pressure (BP), body composition and body mass index (BMI). Two hundred thirty‐eight
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Recent advances in the genetics of preterm birth. Ann. Hum. Genet. (IF 1.368) Pub Date : 2019-12-19 Megan Wadon,Neena Modi,Hilary S Wong,Anita Thapar,Michael C O'Donovan
Preterm birth is associated with short- and long-term impairments affecting physical, cognitive, and neuropsychiatric health. These sequelae, together with a rising preterm birth rate and increased survival, make prematurity a growing public health issue because of the increased number of individuals with impaired health throughout the life span. Although a major contribution to preterm birth comes
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Thousands of missing variants in the UK Biobank are recoverable by genome realignment. Ann. Hum. Genet. (IF 1.368) Pub Date : 2020-03-31 Tongqiu Jia,Brenton Munson,Hana Lango Allen,Trey Ideker,Amit R Majithia
The UK Biobank is an unprecedented resource for human disease research. In March 2019, 49,997 exomes were made publicly available to investigators. Here we note that thousands of variant calls are unexpectedly absent from this dataset, with 641 genes showing zero variation. We show that the reason for this was an erroneous read alignment to the GRCh38 reference. The missing variants can be recovered
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The association of the UHRF1BP1 gene with systemic lupus erythematosus was replicated in a Han Chinese population from mainland China. Ann. Hum. Genet. (IF 1.368) Pub Date : 2019-11-05 Leilei Wen,Lu Liu,Xue Shen,Hui Li,Zhengwei Zhu,He Huang,Minglong Cai,Danfeng Qian,Songke Shen,Ying Qiu,Yong Cui,Yujun Sheng
Single-nucleotide polymorphisms (SNPs) in the UHRF gene have been shown to be associated with systemic lupus erythematosus (SLE) in European and Hong Kong Chinese, but statistically significant evidence for association has not been found in a mainland Han Chinese population. Therefore, we selected SNP rs13205210 located in UHRF1BP1 as a candidate association from our previously published genome-wide
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Chorionic villus sampling experience of a reference perinatal medicine center. Ann. Hum. Genet. (IF 1.368) Pub Date : 2019-12-04 M Sinan Beksaç,Canan Unal,Atakan Tanacan,Erdem Fadiloglu,Ayşe Nur Çakar
To share the chorionic villus sampling (CVS) experience of a single surgeon in our institution.
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Association study of the single-nucleotide polymorphisms -3971G/A and +276G/T in the adiponectin gene with type 2 diabetes in a North Indian Punjabi population. Ann. Hum. Genet. (IF 1.368) Pub Date : 2019-11-21 Veena Bains,Harjit Kaur,Badaruddoza
OBJECTIVE To investigate the role of ADIPOQ gene variants (-3971G/A rs822396 and +276G/T rs1501299) with type 2 diabetes risk in a North Indian Punjabi population. METHODS Adiponectin is one of the most abundant circulating adipocytokines in the human body that plays an important role in the metabolic processes and positively regulates energy homeostasis and insulin secretion. Several studies have
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Molecular and geographical heterogeneity of hemoglobinopathy mutations in Azerbaijanian populations. Ann. Hum. Genet. (IF 1.368) Pub Date : 2019-11-21 Gunay Aliyeva,Chingiz Asadov,Tahira Mammadova,Surmaya Gafarova,Yegana Guliyeva,Eldar Abdulalimov
With the carrier rate of 4%-8.6%, β-thalassemia is one of the most prevalent hereditary disorders in Azerbaijan. Taking into consideration the high frequency of β-thalassemia as well as the occurrences of several other hemoglobinopathies, we conducted a large genotyping study to investigate the mutational background of common hemoglobinopathies in the country. Α- and β-globin genes were evaluated in
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FAAH levels and its genetic polymorphism association with susceptibility to methamphetamine dependence. Ann. Hum. Genet. (IF 1.368) Pub Date : 2019-12-02 Wei Zhang,Huan Liu,Xiao-Dong Deng,Ying Ma,Yun Liu
The fatty acid amide hydrolase (FAAH) gene was involved in the modulation of reward and addiction pathophysiology of illicit drugs abuse, and its polymorphisms might be associated with risk of methamphetamine (METH) dependence. This study aimed to investigate the FAAH mRNA levels in peripheral blood mononuclear cells and plasma protein levels and to analyze the 385C/A polymorphism (rs324420) between
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DNAH17 is associated with asthenozoospermia and multiple morphological abnormalities of sperm flagella. Ann. Hum. Genet. (IF 1.368) Pub Date : 2019-12-16 Yanwei Sha,Xiaoli Wei,Lu Ding,Libin Mei,Xianjing Huang,Shaobin Lin,Zhiying Su,Lingyuan Kong,Yi Zhang,Zhiyong Ji
Multiple morphological abnormalities of the sperm flagella (MMAF) is one kind of severe asthenozoospermia, which is caused by dysplastic development of sperm flagella. In our study, we sought to investigate the novel gene mutations leading to severe asthenozoospermia and MMAF.
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General regression model: A "model-free" association test for quantitative traits allowing to test for the underlying genetic model. Ann. Hum. Genet. (IF 1.368) Pub Date : 2019-12-13 Emilie Gloaguen,Marie-Hélène Dizier,Mathilde Boissel,Ghislain Rocheleau,Mickaël Canouil,Philippe Froguel,Jean Tichet,Ronan Roussel,,Cécile Julier,Beverley Balkau,Flavie Mathieu
Most genome‐wide association studies used genetic‐model‐based tests assuming an additive mode of inheritance, leading to underpowered association tests in case of departure from additivity. The general regression model (GRM) association test proposed by Fisher and Wilson in 1980 makes no assumption on the genetic model. Interestingly, it also allows formal testing of the underlying genetic model. We
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Weighted burden analysis of exome-sequenced late-onset Alzheimer's cases and controls provides further evidence for a role for PSEN1 and suggests involvement of the PI3K/Akt/GSK-3β and WNT signalling pathways. Ann. Hum. Genet. (IF 1.368) Pub Date : 2020-02-05 David Curtis,Kaushiki Bakaya,Leona Sharma,Sreejan Bandyopadhyay
Previous studies have implicated common and rare genetic variants as risk factors for late-onset Alzheimer's disease (LOAD). Here, weighted burden analysis was applied to over 10,000 exome-sequenced subjects from the Alzheimer's Disease Sequencing Project. Analyses were carried out to investigate whether rare variants predicted to have a functional effect within a gene were more commonly seen in cases
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Mapping the TYR gene reveals novel and previously reported variants in Eastern Indian patients highlighting preponderance of the same changes in multiple unrelated ethnicities. Ann. Hum. Genet. (IF 1.368) Pub Date : 2020-03-02 Kausik Ganguly,Tithi Dutta,Arpan Saha,Devroop Sarkar,Asim Sil,Kunal Ray,Mainak Sengupta
Oculocutaneous albinism (OCA) is a group of congenital autosomal recessive disorders with seven known subtypes (OCA1-OCA7) characterized by loss or absence of pigmentation in the skin, hair, and eyes. OCA1, caused by pathogenic variations in the tyrosinase (TYR) gene, has been documented to be the most prevalent subtype across the world including India. In the present study, we recruited 53 OCA-affected
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Inhibition of miR-499-5p expression improves nonalcoholic fatty liver disease. Ann. Hum. Genet. (IF 1.368) Pub Date : 2020-01-20 Hanyun Liu,Ting Wang,Xi Chen,Jing Jiang,Nianhua Song,Ran Li,Yongning Xin,Shiying Xuan
OBJECTIVE Nonalcoholic fatty liver disease (NAFLD) is one of the leading causes of chronic liver diseases. However, the pathogenesis of NAFLD is largely unknown. Here, we investigated the specific role of miR-499-5p in NAFLD. METHODS Free fatty acid was used to induce HL-7702 cell line to establish a NAFLD cell model, and animal models of NAFLD were constructed by feeding C57BL/6 mice with a high-fat
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A novel mutation of Twinkle in Perrault syndrome: A not rare diagnosis? Ann. Hum. Genet. (IF 1.368) Pub Date : 2020-04-12 Fabio Gotta,Merit Lamp,Alessandro Geroldi,Lucia Trevisan,Paola Origone,Giuseppina Fugazza,Sabrina Fabbri,Claudia Nesti,Anna Rubegni,Federica Morani,Filippo Maria Santorelli,Emilia Bellone,Paola Mandich
Perrault syndrome is a rare disorder characterized by ovarian dysgenesis, bilateral sensorineural hearing loss and associated with mutations in six mitochondrial proteins. Additional neurological features were also described. Herein, we report on a 27‐year‐old woman with Perrault syndrome (PS), moderate ataxia and axonal sensory‐motor peripheral neuropathy in whom we identified compound heterozygous
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Clinical and molecular aspects of PTEN mutations in 10 pediatric patients. Ann. Hum. Genet. (IF 1.368) Pub Date : 2020-03-12 Esra Isik,Ozguc Semih Simsir,Asli Ece Solmaz,Huseyin Onay,Tahir Atik,Ayca Aykut,Asude Durmaz,Ozgur Cogulu,Ferda Ozkinay
PTEN gene mutations are responsible for the PTEN hamartoma tumor syndrome (PHTS). In this study, clinical and molecular findings of patients carrying PTEN mutations are presented. Our aim is to contribute to genotype–phenotype correlation and define the most common findings of the syndrome in pediatric patients.
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Three patients with 46,X,inv(Y)(p11.2q11.2)pat/45,X and their pedigree analysis. Ann. Hum. Genet. (IF 1.368) Pub Date : 2020-03-12 Yunchun Chen,Yuni Xu,Xiaoqiang Cao,Chunqiao Zheng,Liying Lin,Zhongyuan Zhu,Jiandong Hu
The present study aimed to perform chromosome examination and pedigree analysis on three patients with semen abnormality who had undergone in vitro fertilization–embryo transfer (IVF‐ET). Peripheral blood cell culture and chromosome karyotyping were performed on 4,200 individuals who had undergone chromosome examination. Among them, 155 pregnant women who had successfully conceived were subjected to
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Novel variant p.(Ala102Thr) in SDHB causes mitochondrial complex II deficiency: Case report and review of the literature. Ann. Hum. Genet. (IF 1.368) Pub Date : 2020-03-02 Parneet Kaur,Suvasini Sharma,Rajagopal Kadavigere,Katta Mohan Girisha,Anju Shukla
Leigh syndrome is a clinically and radiologically heterogeneous condition with approximately 75 genes, nuclear and mitochondrial, known to be implicated in its pathogenesis. Leigh syndrome due to complex II deficiency constitutes 2% to 7% of these cases. Previously, nine individuals with Leigh syndrome have been reported with pathogenic variants in SDHB , which encodes for the iron–sulfur cluster subunit
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Genetic structure of the ethnic Lao groups from mainland Southeast Asia revealed by forensic microsatellites. Ann. Hum. Genet. (IF 1.368) Pub Date : 2020-03-02 Suparat Srithawong,Kanha Muisuk,Metawee Srikummool,Narongdet Mahasirikul,Saksuriya Triyarach,Kamnikone Sriprasert,Wibhu Kutanan
Laotians and Lao Isan are widely spread Lao groups who live in Laos and northeastern Thailand, respectively. We explored the genetic structure between them and other ethnic groups from Thailand to clarify historical patterns of admixture between Tai‐Kadai and Austroasiatic speakers, and to expand the forensic reference database for the region.
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Editorial: Topical ethical issues in the publication of human genetics research. Ann. Hum. Genet. (IF 1.368) Pub Date : 2020-02-24 David Curtis,François Balloux
The original name of the Annals of Human Genetics was the Annals of Eugenics and the early contributors to the journal had a historical involvement with what was to become the eugenics movement. In this context, the Annals bears a special responsibility to promote the highest ethical standards and to look closely at its own role as a publisher of genetics research. This may extend beyond complying
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Homozygous in-frame variant of SCL6A3 causes dopamine transporter deficiency syndrome in a consanguineous family. Ann. Hum. Genet. (IF 1.368) Pub Date : 2020-02-20 Erfan Heidari,Ehsan Razmara,Sareh Hosseinpour,Ali Reza Tavasoli,Masoud Garshasbi
The human dopamine transporter (hDAT) participates in dopamine homeostasis by clearing dopamine from the extracellular space using secondary active transport. Dysregulation of hDAT has been reported to be associated with different neuropsychiatric disorders. Dopamine transporter deficiency syndrome (DTDS) is a complex disease caused by defects in dopamine uptake within the synaptic cleft and patients
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LD scores are associated with differences in allele frequencies between populations but LD score regression can still distinguish confounding from polygenicity. Ann. Hum. Genet. (IF 1.368) Pub Date : 2020-01-11 Mason Alexander,David Curtis
The linkage disequilibrium (LD) score regression method tests whether there is an association between the LD score and allele frequency differences between cases and controls. It makes the assumption that there is no association between LD score and allele frequency differences among populations and hence that any observed association is the result of a polygenic effect rather than population stratification
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A novel mutation combining with rs66612022 in a Chinese pedigree suggests a new pathogenesis to osteogenesis imperfecta via whole genome sequencing. Ann. Hum. Genet. (IF 1.368) Pub Date : 2019-12-18 Yanjiao Li,Hongsuo Liang,Dekai Yuan,Baoling Liu,Ling Liu,Yongfa Zhang,Kaiyu Hou,Yunchao Zhang,Bin Chen,Jing Ding,Yunxia Li,Qilin Wang,Haiying Wu,Hong Shi,Min Hu
Osteogenesis imperfecta (OI) is a rare heritable disease with systemic connective tissue disorder. Most of the patients represent autosomal dominant form of OI, and are usually resulting from the mutations in type I collagen genes. However, the gene mutations reported previously only account for ∼70% of the OI cases. Here, in a Chinese OI family, we examined seven patients and nine normal individuals
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Improved assembly and variant detection of a haploid human genome using single-molecule, high-fidelity long reads. Ann. Hum. Genet. (IF 1.368) Pub Date : 2019-11-11 Mitchell R Vollger,Glennis A Logsdon,Peter A Audano,Arvis Sulovari,David Porubsky,Paul Peluso,Aaron M Wenger,Gregory T Concepcion,Zev N Kronenberg,Katherine M Munson,Carl Baker,Ashley D Sanders,Diana C J Spierings,Peter M Lansdorp,Urvashi Surti,Michael W Hunkapiller,Evan E Eichler
The sequence and assembly of human genomes using long-read sequencing technologies has revolutionized our understanding of structural variation and genome organization. We compared the accuracy, continuity, and gene annotation of genome assemblies generated from either high-fidelity (HiFi) or continuous long-read (CLR) datasets from the same complete hydatidiform mole human genome. We find that the
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Intrauterine phenotype features of fetuses with Williams-Beuren syndrome and literature review. Ann. Hum. Genet. (IF 1.368) Pub Date : 2019-11-11 Meizhen Yuan,Linbei Deng,Yingjun Yang,Luming Sun
Williams-Beuren syndrome (WBS) is a well-defined multisystem chromosomal disorder that is caused by a chromosome 7q11.23 region heterozygous deletion. We explored prenatal diagnosis of WBS by ultrasound as well as multiple genetic methods to characterize the structural variants of WBS prenatally. Expanded noninvasive prenatal testing (NIPT-plus) was elected as a regular prenatal advanced screen for
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Variant frequencies of KCNQ1, KCNH2, and SCN5A in a Chinese inherited arrhythmia cohort and other disease cohorts undergoing genetic testing. Ann. Hum. Genet. (IF 1.368) Pub Date : 2019-11-07 Xin Li,Nian Liu,Rong Bai
KCNQ1, KCNH2, and SCN5A are the most common genes responsible for long QT syndrome and Brugada syndrome. However, the genetic variant frequencies of the three genes in different Chinese disease cohorts are largely unknown. In this study, we analyzed the genetic variants of KCNQ1, KCNH2, and SCN5A in patients from seven cohorts (total N = 11945, including patients clinically suspected to have inherited
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Application of targeted exome and whole-exome sequencing for Chinese families with Stargardt disease. Ann. Hum. Genet. (IF 1.368) Pub Date : 2019-11-01 Handong Dan,Xin Huang,Yiqiao Xing,Yin Shen
OBJECTIVE The aim of this study was to investigate pathogenic variants and molecular etiologies of Stargardt disease (STGD) in a cohort of Chinese families. MATERIALS AND METHODS A cohort of 12 unrelated STGD families diagnosed on the basis of clinical manifestations underwent analysis by targeted exome or whole-exome sequencing. Bioinformatics analysis, Sanger sequencing, and cosegregation analysis
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5α-Reductase type 2 deficiency in families from an isolated Andean population in Venezuela. Ann. Hum. Genet. (IF 1.368) Pub Date : 2019-10-15 Andrea Avendaño,Mercedes González-Coira,Irene Paradisi,Ascanio Rojas,Gloria Da Silva,Roald Gómez-Pérez,Jesús Osuna Ceballos
5α-Reductase type 2 deficiency causes a 46,XY disorder of sex development (DSD) characterized by ambiguous external genitalia, rudimentary prostate, and normal internal genitalia. The disease prevalence worldwide is low, but in a small and isolated village of the Venezuelan Andes, a higher incidence has been found. DNA analysis of the SRD5A2 gene was performed in three inbred affected individuals clinically
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MTF1 binds to metal-responsive element e within the ATP7B promoter and is a strong candidate in regulating the ATP7B expression. Ann. Hum. Genet. (IF 1.368) Pub Date : 2019-10-09 Amelie Stalke,Eva-Doreen Pfister,Ulrich Baumann,Thomas Illig,Eva Reischl,Maria Sandbothe,Beate Vajen,Nicole Huge,Brigitte Schlegelberger,Nils von Neuhoff,Britta Skawran
Wilson's disease is an autosomal recessive disorder resulting from copper excess. Some patients with clinical Wilson's disease symptoms exhibit no or only heterozygous pathogenic variants in the coding region of the disease-causing ATP7B gene. Therefore, the ATP7B promoter region is of special interest. Metal-responsive elements (MREs) located in the ATP7B promoter are promising motifs in modulating
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In silico analysis of nonsynonymous single-nucleotide polymorphisms (nsSNPs) of the SMPX gene. Ann. Hum. Genet. (IF 1.368) Pub Date : 2019-10-03 Md Arifuzzaman,Sarmistha Mitra,Raju Das,Amir Hamza,Nurul Absar,Raju Dash
Mutations in the SMPX gene can disrupt the regular activity of the SMPX protein, which is involved in the hearing process. Recent reports showing a link between nonsynonymous single-nucleotide polymorphisms (nsSNPs) in SMPX and hearing loss, thus classifying deleterious SNPs in SMPX will be an uphill task before designing a more extensive population study. In this study, damaging nsSNPs of SMPX from
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Xq26 duplications lead to undergrowth or overgrowth via competing pathways including GPC3/GPC4. Ann. Hum. Genet. (IF 1.368) Pub Date : 2019-10-03 Gaurav K Karna,Kenneth A Myers
The Xq26 locus has importance in human growth with multiple genes and regions playing important roles, which potentially leads to macrosomia or microsomia if disrupted. One region of Xq26.2 comprises the genes GPC3 and GPC4; deletion or duplication of this region has been recently been shown to result in overgrowth, specifically Simpson-Golabi-Behmel syndrome. We describe a male patient with two maternally
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The role of genetics and epigenetics in the pathogenesis of gestational diabetes mellitus. Ann. Hum. Genet. (IF 1.368) Pub Date : 2019-10-01 Jakub Rosik,Bartosz Szostak,Filip Machaj,Andrzej Pawlik
Diabetes mellitus (DM) is a heterogeneous group of disorders whose common trait is chronic hyperglycemia. Gestational diabetes mellitus (GDM) is one of the subtypes of DM that manifests during pregnancy. It is believed that 2%-5% of pregnancies worldwide are complicated with GDM, with the prevalence having significantly increased over the last decade. While the pathogenesis of the disease remains largely
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Total genotype score and athletic status: An exploratory cross-sectional study of a Brazilian athlete cohort. Ann. Hum. Genet. (IF 1.368) Pub Date : 2019-10-01 João Paulo Limongi França Guilherme,Antonio Herbert Lancha
The purpose of the present study was to explore the ability of the total genotype score (TGS) for evaluation of the polygenic profile of elite athletes. Data from a Brazilian athlete cohort were used in this study, which included 368 athletes and 818 nonathletes. The TGS targeted to power athletes was computed using from two to 10 associated polymorphisms. In all models, the power group showed a higher
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A novel homozygous LRRK1 stop gain mutation in a patient suspected with osteosclerotic metaphyseal dysplasia. Ann. Hum. Genet. (IF 1.368) Pub Date : 2019-09-30 Mohammad Miryounesi,Ali Nikfar,Majid Changi-Ashtiani,Mohammad Shahrooei,Hossein Dinmohammadi,Tina Shahani,Samira Zarvandi,Tahereh Bahrami,Mana Momenilandi,Hassan Rokni-Zadeh
Osteosclerotic metaphyseal dysplasia (OSMD) is a very rare autosomal-recessive disorder and a distinctive type of osteopetrosis, characterized mainly by skeletal fractures and deformity, osteosclerosis, and sometimes hypotonia, developmental delay, and seizures. Sequence variants in the leucine-rich repeat kinase 1 (LRRK1) gene underlying OSMD have been reported previously. In the present study, we
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Mediterranean fever (MEFV) gene profile and a novel missense mutation (P313H) in Iranian Azari-Turkish patients. Ann. Hum. Genet. (IF 1.368) Pub Date : 2019-09-11 Leila Rostamizadeh,Leila Vahedi,Seied Rafi Bahavarnia,Shahriar Alipour,Somayeh Abolhasani,Alireza Khabazi,Ebrahim Sakhinia
BACKGROUND Familial Mediterranean fever (FMF) is common in Azari-Turkish people, one of the biggest ethnic groups in Iran. In this study, we sought to investigate the mutation spectrum of the MEFV gene and any genotype-phenotype correlations. METHODS AND MATERIALS 400 unrelated Azari-Turkish FMF patients were analyzed in this study. Mutations in exons 2, 3, 5, and 10 of the MEFV gene were investigated
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GJB2-related hearing loss in central Iran: Review of the spectrum and frequency of gene mutations. Ann. Hum. Genet. (IF 1.368) Pub Date : 2019-09-11 Mahbobeh Koohiyan,Farideh Koohian,Fatemeh Azadegan-Dehkordi
Mutations in the GJB2 gene are a main cause of autosomal-recessive nonsyndromic hearing loss (ARNSHL) in many populations. Previous studies have estimated the average frequency of GJB2 mutations to be ∼16% in Iran, but would vary among different ethnic groups. Here, we have taken together and reviewed results from our two previous publications and data from searching other published mutation reports
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A homozygous mutation in CMAS causes autosomal recessive intellectual disability in a Kazakh family. Ann. Hum. Genet. (IF 1.368) Pub Date : 2019-09-08 Ronggui Qu,Qing Sang,Xueqian Wang,Yao Xu,Biaobang Chen,Jian Mu,Zhihua Zhang,Li Jin,Lin He,Lei Wang
Intellectual disability (ID) describes a wide range of serious human diseases caused by defects in central nervous system development and function. Some mutant genes have been found to be associated with these diseases, but not all cases can be explained, thus suggesting that other disease-causing genes have not yet been discovered. Sialic acid is involved in a number of key biological processes, including
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Integrative analysis of genome-wide association study and expression quantitative trait loci datasets identified various immune cell-related pathways for rheumatoid arthritis. Ann. Hum. Genet. (IF 1.368) Pub Date : 2019-09-04 Ping Li,Xi Wang,Xiong Guo,Yan Wen,Li Liu,Xiao Liang,Yanan Du,Cuiyan Wu,Sen Wang,Feng Zhang
Rheumatoid arthritis (RA) is an autoimmune chronic disorder manifesting as warm, swollen, and painful joints. Multiple immune cells are implicated in the development of RA. Previous studies demonstrated that integrating the genetic information of genome-wide association studies (GWAS) and expression quantitative trait loci (eQTLs) is capable of identifying new disease-risk loci and providing novel
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A novel mutation of MSX1 inherited from maternal mosaicism causes a severely affected child with nonsyndromic oligodontia. Ann. Hum. Genet. (IF 1.368) Pub Date : 2019-08-30 Tengfei Ma,Yi Liu,Xiaoxue Zhao,Jing Wu,Huijuan Wang,Jing Chen,Peiwen Liu,Xu Zhang,Xiangyu Zhang
Mutations of MSX1 have been associated with nonsyndromic hypodontia. To seek the causal gene mutation sites in a family with nonsyndromic oligodontia, whole-exome sequencing (WES) was performed to seek the causative locus of the family. The candidate mutation was further identified by Sanger sequencing afterward. Two mutations of MSX1 were found both in the proband and her mother. One novel heterozygous
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Argentinian clinical genomics in a leukodystrophies and genetic leukoencephalopathies cohort: Diagnostic yield in our first 9 years. Ann. Hum. Genet. (IF 1.368) Pub Date : 2019-08-16 Leila Cohen,Analisa Manín,Nancy Medina,Sergio Rodríguez-Quiroga,Dolores González-Morón,Julieta Rosales,Hernan Amartino,Norma Specola,Marta Córdoba,Marcelo Kauffman,Patricia Vega
INTRODUCTION AND OBJECTIVES Leukodystrophies and genetic leukoencephalopathies constitute a vast group of pathologies of the cerebral white matter. The large number of etiopathogenic genes and the frequent unspecificity on the clinical-radiological presentation generate remarkable difficulties in the diagnosis approach. Despite recent and significant developments, molecular diagnostic yield is still
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