Rachel Z Blumhagen, David A Schwartz, Carl D Langefeld, Tasha E Fingerlin
Aggregate tests of rare variants are often employed to identify associated regions compared to sequentially testing each individual variant. When an aggregate test is significant, it is of interest to identify which rare variants are "driving" the association. We recently developed the rare variant influential filtering tool (RIFT) to identify influential rare variants and showed RIFT had higher true positive rates compared to other published methods. Here we use importance measures from the standard random forest (RF) and variable importance weighted RF (vi-RF) to identify influential variants...
May 23, 2023: Annals of Human Genetics
Ayesha Siddique, Warda Fatima, Naeem Shahid
BRCA1 variants are extensively associated with increased risk of breast cancer. Early detection and screening of variants is still rare in developing countries. Here, we investigated six BRCA1 variants in 300 subjects from Pakistani population using tetra amplification-refractory mutation system (T-ARMS) PCR. Our results indicate significant association of BRCA1 variants rs8176237 (AA; OR 8.2, 95% CI 3.02-22.64, p < 0.0001), rs1060915 (CC; OR 4.29, 95% CI 1.94-9.48, p = 0.0003), and rs799912 (TT; OR 3...
May 16, 2023: Annals of Human Genetics
José R Sandoval, Susana Revollo, Cinthia Cuellar, Daniela R Lacerda, Marilza S Jota, Ricardo Fujita, Fabricio R Santos
During the colonial period in South America, many autochthonous populations were affected by relocation by European missionary reductions and other factors that impacted and reconfigured their genetic makeup. Presently, the descendants of some "reduced" and other isolated groups are distributed in the Amazonian areas of Peru, Bolivia, and Brazil, and among them, speakers of Takanan and Panoan languages. Based on linguistics, these peoples should be closely related, but so far no DNA comparison studies have been conducted to corroborate a genetic relationship...
May 10, 2023: Annals of Human Genetics
Sarah Orr, Eric Olinger, Sotia Iosifidou, Miguel Barroso-Gil, Ruxandra Neatu, Katrina Wood, Ian Wilson, John Andrew Sayer
INTRODUCTION: Massively parallel sequencing (MPS) techniques have made a major impact on the identification of the genetic basis of inherited kidney diseases such as the ciliopathy autosomal dominant polycystic kidney disease (ADPKD). Great care must be taken when analysing MPS data in isolation from accurate phenotypic information, as this can cause misdiagnosis. METHODS: Here, we describe a family trio, recruited to the Genomics England 100,000 Genomes Project, labelled as having cystic kidney disease, who were genetically unsolved following routine data analysis pipelines...
April 12, 2023: Annals of Human Genetics
Jiayan Liu, Hanfei Xu, L Adrienne Cupples, George T O' Connor, Ching-Ti Liu
INTRODUCTION: Observational studies have shown that body mass index (BMI) and waist-to-hip ratio (WHR) are both inversely associated with lung function, as assessed by forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1). However, observational data are susceptible to confounding and reverse causation. METHODS: We selected genetic instruments based on their relevant large-scale genome-wide association studies. Summary statistics of lung function and asthma came from the UK Biobank and SpiroMeta Consortium meta-analysis (n = 400,102)...
April 3, 2023: Annals of Human Genetics
Sachiko Miyamoto, Kazuyuki Nakamura, Mitsuhiro Kato, Mitsuko Nakashima, Hirotomo Saitsu
Biallelic CC2D2A variants are associated with a wide range of neurodevelopmental disorders including Meckel syndrome. Here we report a Japanese girl with Meckel syndrome harboring a pathogenic deep intronic variant (NM_001378615.1:c.1149+3569A>G) and an exonic LINE-1 insertion, which was predicted to cause aberrant splicing by SpliceAI and was detected by TEMP2 program, respectively. RNA analysis using urine-derived cells (UDCs) showed retention of 149-bp intronic sequences, leading to frameshift. Immunoblotting showed marked reduction of CC2D2A protein in the patient...
March 27, 2023: Annals of Human Genetics
Mai Abd El Salam, Khaled Salama, Yasmeen M M Selim, Mariam Saad, Rasha Rady, Salem Alawbathani, Sabine Schroeder, Mohamed A Elmonem, Nour Elkhateeb
INTRODUCTION: Congenital sideroblastic anemias (CSAs) are a group of inherited bone-marrow disorders manifesting with erythroid hyperplasia and ineffective erythropoiesis. METHODS: We describe a detailed clinical and genetic characterization of three siblings with CSA. RESULTS: Two of them had limb-girdle myopathy and global developmental delay. The two elder siblings performed allogenic hematopoietic stem-cell transplantation 5 and 3 years prior with stabilization of the hematological features...
March 14, 2023: Annals of Human Genetics
Mengyuan Liu, Bing Li, Xiaona Wang, Dongxiao Li, Zhenhua Xie, Yuke Li, Yang Gao, Baiyun Chen, Huichun Zhang, Yanli Wang, Chao Gao
OBJECTIVE: The objective of this study was to investigate the pathogenesis and inheritance pattern of a Chinese Han family with hereditary spastic paraplegia and to retrospectively analyze the characteristics of KIF1A gene variants and related clinical manifestations. METHODS: High-throughput whole-exome sequencing was performed on members of a Chinese Han family with a clinical diagnosis of hereditary spastic paraplegia, and the sequencing results were validated by Sanger sequencing...
March 10, 2023: Annals of Human Genetics
Oscar Alonso-Luna, Gabriela E Mercado-Celis, Jorge Melendez-Zajgla, Marta Zapata-Tarres, Elvia Mendoza-Caamal
Childhood cancer is a leading cause of death by disease in children ages 5-14, for which there are no preventive strategies. Due to early-age of diagnosis and short period of exposure to environmental factors, increasing evidence suggests childhood cancer could have strong association with germline alterations in predisposition cancer genes but, their frequency and distribution are largely unknown. Several efforts have been made to develop tools to identify children with increased risk of cancer who may benefit from genetic testing but their validation and application on a large scale is necessary...
March 10, 2023: Annals of Human Genetics
Feyzanur Yildirimtepe Caldiran, Koksal Deveci, Ercan Cacan
Familial Mediterranean fever (FMF) is an autoinflammatory disease caused by variations in the MEFV gene, which encodes the pyrin protein, a member of the inflammasomes. Despite the complex pathogenesis of FMF, epigenetic changes also play roles in the disease progression. In our previous study, we observed a relationship between NLRP13, which is one of the members of the inflammasome complex and has a pyrin domain in its structure, and the MEFV gene using the STRING database. In this study, we examined NLRP13 expression and methylation status in 40 patients with FMF attack and 20 healthy individuals...
May 2023: Annals of Human Genetics
(no author information available yet)
No abstract text is available yet for this article.
March 2023: Annals of Human Genetics
Sanaz Mohammadi, Hossein Jafari Khamirani, Maryam Baneshi, Neda Kamal, Jamal Manoocheri, Mahsa Saffar, Mehdi Dianatpour, Seyed Mohammad Bagher Tabei, Seyed Alireza Dastgheib
Introduction Hereditary sensory neuropathy (HSN) describes as a heterogeneous group of peripheral neuropathies. HSN type 1 (HSN1) is one subtype characterized by distal sensory impairment that occurs in the form of numbness, tingling, or pain. To date, only two variants in the atlastin GTPase 3 (ATL3) gene have been identified that result in hereditary sensory neuropathy type 1F (HSN1F) with autosomal dominantinheritance. Methods We sudied and examined who present with sensory disturbances and muscle weakness in their lower limb...
March 1, 2023: Annals of Human Genetics
Pinyaphat Khamphikham, Oravee Hanmanoviriya, Somsakul Pop Wongpalee, Thongperm Munkongdee, Kittiphong Paiboonsukwong, Yupin Jopang, Chaowanee Wangchauy, Charan Sancharernsook, Nathawat Jinorose, Sakorn Pornprasert
INTRODUCTION: The α0 -thalassemia 44.6 kb or Chiang Rai (--CR ) deletion has been reported in northern Thailand and is capable of causing hemoglobin (Hb) H disease and a lethal α-thalassemia genotype, Hb Bart's hydrops fetalis, in this region. However, there are no current data regarding the frequency of --CR nationwide due to a lack of effective diagnostic assay. Therefore, this study aimed to develop a reliable platform for simultaneous genotyping of --CR and two common α0 -thalassemias in Thailand (--SEA and --THAI ) and investigate the frequency of --CR across Thailand...
January 29, 2023: Annals of Human Genetics
Massimo Mezzavilla, Massimiliano Cocca
BACKGROUND: How much are natural selection and gene characteristics, such as the number of protein-protein interactions (PPIs), tissue specificity (𝞽), and expression level, connected? METHODS: In order to investigate these relationships, we combined different metrics linked to genetic constraints and analyzed their distribution concerning PPIs, 𝞽 and expression levels. RESULTS: We discovered a positive correlation between genetic constraints, PPIs, and expression levels in all tissues...
January 27, 2023: Annals of Human Genetics
Angela M Zigarelli, Hanna M Venera, Brody A Receveur, Jack M Wolf, Jason Westra, Nathan L Tintle
As biobanks become increasingly popular, access to genotypic and phenotypic data continues to increase in the form of precomputed summary statistics (PCSS). Widespread accessibility of PCSS alleviates many issues related to biobank data, including that of data privacy and confidentiality, as well as high computational costs. However, questions remain about how to maximally leverage PCSS for downstream statistical analyses. Here we present a novel method for testing the association of an arbitrary number of single nucleotide variants (SNVs) on a linear combination of phenotypes after adjusting for covariates for common multimarker tests (e...
January 22, 2023: Annals of Human Genetics
Büşranur Çavdarlı, Özlem Yayici Köken, Saide Betül Arslan Satılmış, Şule Bilen, Didem Ardıçlı, Ahmet Cevdet Ceylan, Cavidan Nur Semerci Gündüz, Haluk Topaloğlu
Muscular dystrophies are a heterogeneous group of neuromuscular disorders with a wide range of the clinical and genetic spectrum. Whole-exome sequencing (WES) has been on the rise to become the usual method of choice for molecular diagnosis in patients presenting with muscular dystrophy or congenital or metabolic myopathy phenotype. Here, we used a panel with 47 genes including not only muscular dystrophy but also myopathy-associated genes that had been used as a first-tier approach. A total of 146 patients who were referred to our clinic with the prediagnosis of muscular dystrophy and/or myopathy were included in the study...
December 27, 2022: Annals of Human Genetics
Die Hu, Shuyue Chen, Hong Zhang
It is of great interest to detect missing heritability for human complex traits. Additive genetic effects (ADD), maternal genetic effects (MGE), and parent-of-origin effects (POE) play important roles in genetic mechanisms. Methods have been developed in the literature to analyze heritabilities due to ADD, POE, and MGE separately but not simultaneously. In this paper, a new model termed APM is proposed based on mother-child duos genetic data, which orthogonally decomposes heritabilities due to ADD, POE, and MGE...
December 23, 2022: Annals of Human Genetics
Yanjiao Li, Qi Liu, Qiuye Ma, Zhaoxia Ma, Juan Chen, An Yu, Changguo Ma, Lihua Qiu, Hong Shi, Hongsuo Liang, Min Hu
BACKGROUND: Primary osteoporosis is a systemic skeletal disease characterized by reduced bone mass and vulnerability to fractures. The genetics of osteoporosis in the Chinese population remain unclear, which hinders the prevention and treatment of osteoporosis in China. This study aimed to explore the susceptibility genes and the roles played by their variants in osteoporosis. METHODS: Blood samples were collected from 45 osteoporosis patients and 30 healthy individuals, and genome-wide association study was performed on array data...
December 8, 2022: Annals of Human Genetics
Naci Cine, Cansu Ugurtas, Merve Gokbayrak, Duygu Aydin, Gulhan Demir, Seda Kuru, Deniz Sunnetci-Akkoyunlu, Seda Eren-Keskin, Turgay Simsek, Devrim Cabuk, Maksut Gorkem Aksu, Nuh Zafer Canturk, Hakan Savli
INTRODUCTION: Breast cancer is the most prevalent malignancy in women worldwide. Although pathogenic variants in the BRCA1/2 genes are responsible for the majority of hereditary breast cancer cases, a substantial proportion of patients are negative for pathogenic variations in these genes. In cancers, the signal transduction pathways of the cell are usually affected first. Therefore, this study aimed to detect and classified genetic variations in non-BRCA signaling genes and investigate the underlying genetic causes of susceptibility to breast cancer...
December 7, 2022: Annals of Human Genetics
Bin Li, Libing Xiao, Danhong Ye, Siyi Zhong, Qiaoyu Yan
INTRODUCTION: After years of development, digital replantation has become a mature treatment. METHODS: Although the NOTUM gene has been shown to be involved in the formation of vertebrate nerves, whether it contributes to the osteogenic mechanism of severed finger replantation remains unknown. In response to this, this study investigates the specific details of NOTUM involvement in replantation of severed fingers. RESULTS: The experimental subjects are patients with replantation of severed fingers from Shulan International Medical College of Shulan (Hangzhou) Hospital affiliated to Zhejiang Shuren University...
December 5, 2022: Annals of Human Genetics
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