Article
Neurosciences
Todd Lencz, Jin Yu, Raiyan Rashid Khan, Erin Flaherty, Shai Carmi, Max Lam, Danny Ben-Avraham, Nir Barzilai, Susan Bressman, Ariel Darvasi, Judy H. Cho, Lorraine N. Clark, Zeynep H. Gumus, Joseph Vijai, Robert J. Klein, Steven Lipkin, Kenneth Offit, Harry Ostrer, Laurie J. Ozelius, Inga Peter, Anil K. Malhotra, Tom Maniatis, Gil Atzmon, Itsik Pe'er
Summary: Identification of rare variants associated with schizophrenia is challenging due to genetic heterogeneity, but in the Ashkenazi Jewish population, cases were found to have a higher frequency of novel MisLoF URVs compared to controls. The burden of MisLoF URVs was inversely correlated with polygenic risk scores in cases. The cadherin gene set was associated with schizophrenia, with a recurrent case mutation in PCDHA3 being linked to cytoplasmic aggregation formation.
Article
Biology
May E. Montasser, Stella Aslibekyan, Vinodh Srinivasasainagendra, Hemant K. Tiwari, Amit Patki, Minoo Bagheri, Tobias Kind, Dinesh Kumar Barupal, Sili Fan, James Perry, Kathleen A. Ryan, Alan R. Shuldiner, Donna K. Arnett, Amber L. Beitelshees, Marguerite Ryan Irvin, Jeffrey R. O'Connell
Summary: This study identified lipid species associated with rare population alleles through a genome-wide association scan of a founder population. The findings highlight the power of founder populations and detailed lipidomics in discovering novel trait-associated variants.
COMMUNICATIONS BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Nikolay A. Barashkov, Fedor A. Konovalov, Tuyara V. Borisova, Fedor M. Teryutin, Aisen V. Solovyev, Vera G. Pshennikova, Nadejda V. Sapojnikova, Lyubov S. Vychuzhina, Georgii P. Romanov, Nyurgun N. Gotovtsev, Igor V. Morozov, Alexander A. Bondar, Fedor A. Platonov, Tatiana E. Burtseva, Elza K. Khusnutdinova, Olga L. Posukh, Sardana A. Fedorova
Summary: A novel pathogenic variant related to the FYCO1 gene was identified in the Yakut population of Eastern Siberia, highlighting the region as having the most extensive accumulation of this unique mutation. This finding sheds significant light on the genetic basis of congenital cataracts among the Yakut people.
EUROPEAN JOURNAL OF HUMAN GENETICS
(2021)
Article
Plant Sciences
Satish Kumar, Cecilia Hong Deng, Martin Hunt, Chris Kirk, Claudia Wiedow, Daryl Rowan, Jun Wu, Lester Brewer
Summary: ROH analysis of different varieties of pear materials revealed genomic regions associated with fruit traits and self-incompatibility traits, suggesting that systematic breeding of European pears may have started earlier than Asian pears. ROH analysis provides a new tool for managing hybrids in gene-banks of self-incompatible plant species and offers a complementary strategy to unravel the genetic architecture of complex traits.
FRONTIERS IN PLANT SCIENCE
(2021)
Article
Medicine, General & Internal
Jan-Bernd Funcke, Barbara Moepps, Julian Roos, Julia von Schnurbein, Kenneth Verstraete, Elke Froehlich-Reiterer, Katja Kohlsdorf, Adriana Nunziata, Stephanie Brandt, Alexandra Tsirigotaki, Ann Dansercoer, Elisabeth Suppan, Basma Haris, Klaus-Michael Debatin, Savvas N. Savvides, I. Sadaf Farooqi, Khalid Hussain, Peter Gierschik, Pamela Fischer-Posovszky, Martin Wabitsch
Summary: This article describes two novel homozygous leptin variants that caused intense hyperphagia, severe obesity, and high leptin levels in two unrelated children. These variants bind to the leptin receptor but have marginal signaling. In the presence of nonvariant leptin, they act as competitive antagonists. High-dose recombinant leptin treatment was initiated and gradually reduced, resulting in near-normal weight for both patients. Antidrug antibodies developed in the patients, but did not appear to affect efficacy. No severe adverse events were observed.
NEW ENGLAND JOURNAL OF MEDICINE
(2023)
Review
Genetics & Heredity
Sanna Gudmundsson, Colleen M. Carlston, Anne O'Donnell-Luria
Summary: Reference population databases such as gnomAD have improved our ability to interpret the human genome, but clonal hematopoiesis (CH) poses challenges in variant interpretation. Somatic variants associated with CH can affect variant frequencies and downstream filtering. Filtering variants or genes associated with CH may inadvertently exclude true germline variants and cause Mendelian conditions. Here, we provide insights and recommendations for interpreting population variant data in genes affected by CH, specifically focusing on 36 established CH genes associated with neurodevelopmental conditions.
Article
Genetics & Heredity
Fei Xie, Shuqi Chen, Peng Liu, Xinhui Chen, Wei Luo
Summary: Heterozygous mutations in SPTAN1 can lead to a wide range of phenotypes, while biallelic mutations may cause autosomal recessive pure hereditary spastic paraplegia. This study reports a patient with complicated HSP likely caused by a novel homozygous SPTAN1 mutation, emphasizing the importance of genetic screening in HSP patients.
JOURNAL OF HUMAN GENETICS
(2022)
Article
Genetics & Heredity
Qingyang Xiao, Volker M. Lauschke
Summary: This study analyzed the genetic variability of genes associated with autosomal recessive disorders across seven ethnogeographic groups, revealing population-specific disease prevalence differences and founder mutations. The research provides valuable insights into epidemiology, complexity, and population-specific effects of autosomal recessive diseases, serving as a useful resource for informing genetic screening programs for clinical geneticists.
NPJ GENOMIC MEDICINE
(2021)
Article
Genetics & Heredity
Yingzhou Wu, Roujia Li, Song Sun, Jochen Weile, Frederick P. Roth
Summary: The study introduces a new method called VARITY, which uses a larger training example pool to improve the accuracy of computational systems in assessing pathogenicity of rare human variants, and excludes features informed by variant annotation and protein identity to reduce bias. VARITY outperformed previous computational methods in identifying pathogenic variants.
AMERICAN JOURNAL OF HUMAN GENETICS
(2021)
Article
Genetics & Heredity
Rui Han, Manman Chu, Jinshuang Gao, Junling Wang, Mengyue Wang, Yichao Ma, Tianming Jia, Xiaoli Zhang
Summary: The mitochondrial protein THG1L plays a crucial role in tRNA maturation process and its malfunction leads to abnormal mitochondrial tRNA modification and neurodevelopmental disorders. A study revealed compound heterozygous variants in THG1L in a 6-year-old boy with cerebellar ataxia, expanding the gene variation and clinical spectrum of THG1L-related cerebellar ataxia. The identified variants impacted the RNA and protein expression of THG1L.
JOURNAL OF HUMAN GENETICS
(2023)
Article
Genetics & Heredity
Michal Levy, Lily Bazak, Noa Lev-El, Rotem Greenberg, Nesia Kropach, Lina Basel-Salmon, Idit Maya
Summary: This study identifies three novel disease-causing variants in the COL4A4 gene that are recurrent among Jews of Bukharian ancestry and cause Alport syndrome in both dominant and recessive autosomal inheritance patterns.
Article
Biochemical Research Methods
Lucas Prates, Renan B. Lemes, Tabita Hunemeier, Florencia Leonardi
Summary: This study aims to solve the problem of identifying homozygosity islands in the genome of individuals in a population. The researchers propose regularized offline change-point methods to detect changes in the parameters of a multidimensional distribution and provide a new methodology for the selection of the regularization constant. The results show good performance in simulations.
Letter
Oncology
Mark D. Ludman, Shira Litz Philipsborn, Shulamit Hartmajer, Nitzan Sharon Shwartzman, Eyal Reinstein
Summary: Mutations in BRCA1 and BRCA2 genes increase the risk of cancers. Recurring BRCA2 mutations were found in the Ethiopian Jewish population in Israel, leading to the decision to expand founder mutation panel to include these mutations. This new panel will enhance genetic testing for at-risk populations.
Article
Biochemistry & Molecular Biology
Ananthapadmanabha Kotambail, Pavalan Selvam, Karthik Muthusamy, Maya Thomas, Sniya Valsa Sudhakar, Chetan Ghati, Sumita Danda, Gautham Arunachal
Summary: This study provides a comprehensive investigation into the pathogenetic mechanism of a novel variant in M/JCD. It shows that the pathogenic variant causes a non-classical splicing defect, which explains the milder phenotype of the disease. The study also suggests the presence of a founder event in the Telugu Devanga Chettiar community, highlighting the importance of carrier screening programs and future therapeutic studies.
EUROPEAN JOURNAL OF HUMAN GENETICS
(2023)
Article
Genetics & Heredity
Michael N. Weedon, Samuel E. Jones, Jacqueline M. Lane, Jiwon Lee, Hanna M. Ollila, Amy Dawes, Jess Tyrrell, Robin N. Beaumont, Timo Partonen, Ilona Merikanto, Stephen S. Rich, Jerome Rotter, Timothy M. Frayling, Martin K. Rutter, Susan Redline, Tamar Sofer, Richa Saxena, Andrew R. Wood
Summary: The effects of previously reported rare genetic variants on extreme sleep conditions and circadian phenotypes are generally less penetrant in the general population, with few highly penetrant associations observed.
Article
Immunology
Evangelos Andreakos, Laurent Abel, Donald C. Vinh, Elzbieta Kaja, Beth A. Drolet, Qian Zhang, Cliona O'Farrelly, Giuseppe Novelli, Carlos Rodriguez-Gallego, Filomeen Haerynck, Carolina Prando, Aurora Pujol, Helen C. Su, Jean-Laurent Casanova, Andras N. Spaan, Paul Bastard, Catherine M. Biggs, Benedetta Bigio, Bertrand Boisson, Alexandre Bolze, Anastasiia Bondarenko, Petter Brodin, Samya Chakravorty, John Christodoulou, Aurelie Cobat, Antonio Condino-Neto, Stefan N. Constantinescu, Hagit Baris Feldman, Jacques Fellay, Rabih Halwani, Emmanuelle Jouanguy, Yu-Lung Lau, Isabelle Meyts, Trine H. Mogensen, Satoshi Okada, Keisuke Okamoto, Tayfun Ozcelik, Qiang Pan-Hammarstrom, Anna M. Planas, Anne Puel, Lluis Quintana-Murci, Laurent Renia, Igor Resnick, Anna Sediva, Anna Shcherbina, Ondrej Slaby, Ivan Tancevski, Stuart E. Turvey, K. M. Furkan Uddin, Diederik van de Beek, Mayana Zatz, Pawel Zawadzki, Shen-Ying Zhang
Summary: SARS-CoV-2 infections can vary greatly between individuals, with some being asymptomatic while others experience life-threatening disease. While 20% of critical COVID-19 cases are due to inborn errors or autoantibodies, the genetic and immunological factors for resistance to infection itself remain unknown. Studies have shown that autosomal recessive deficiencies in certain genes or enzymes can confer resistance to diseases, suggesting a potential strategy for identifying individuals naturally resistant to SARS-CoV-2 infection.
Correction
Immunology
Evangelos Andreakos, Laurent Abel, Donald C. Vinh, Elzbieta Kaja, Beth A. Drolet, Qian Zhang, Cliona O'Farrelly, Giuseppe Novelli, Carlos Rodriguez-Gallego, Filomeen Haerynck, Carolina Prando, Aurora Pujol, Helen C. Su, Jean-Laurent Casanova, Andras N. Spaan
Article
Biochemistry & Molecular Biology
Lin Jiang, Hui Jiang, Sheng Dai, Ying Chen, Youqiang Song, Clara Sze-Man Tang, Shirley Yin-Yu Pang, Shu-Leong Ho, Binbin Wang, Maria-Mercedes Garcia-Barcelo, Paul Kwong-Hang Tam, Stacey S. Cherny, Mulin Jun Li, Pak Chung Sham, Miaoxin Li
Summary: The existing methods for studying rare variants in complex diseases have statistical limitations, but the RUNNER method proposed in this study utilizes genomic features from public data to accurately identify susceptibility genes with rare risk variants for complex diseases.
NUCLEIC ACIDS RESEARCH
(2022)
Letter
Allergy
Jaime S. Rosa Duque, Daniel Leung, Elaine Y. L. Au, Yu-Lung Lau
PEDIATRIC ALLERGY AND IMMUNOLOGY
(2022)
Article
Clinical Neurology
Nader Tarabeih, Alexander Kalinkovich, Adel Shalata, Stacey S. Cherny, Gregory Livshits
Summary: This study found a complex relationship between low back pain (LBP) and mental and metabolic disorders, inflammation-related soluble markers, and body composition parameters. Age, sex, GDF-15, and extracellular water directly influence LBP disability, while mental and metabolic disorders, waist-hip ratio, and follistatin indirectly affect LBP disability.
JOURNAL OF PAIN RESEARCH
(2022)
Article
Genetics & Heredity
Stacey S. Cherny, Frances M. K. Williams, Gregory Livshits
Summary: The present study examines the genetic overlap of metabolic syndrome (MetS) components using quantitative genetic modeling and GWAS analysis. The results demonstrate a modest but significant genetic overlap, suggesting that treating each component individually may be important in the clinical treatment of MetS.
ANNALS OF HUMAN GENETICS
(2022)
Article
Biochemistry & Molecular Biology
Melody Kasher, Frances M. K. Williams, Maxim B. Freidin, Ida Malkin, Stacey S. Cherny, Gregory Livshits
Summary: Rheumatoid arthritis and osteoporosis are two complex inflammatory conditions with shared genetic background and causal relationships. This study aimed to clarify the genetic architecture underlying these conditions and their relationship with C-reactive protein. The findings suggest that RA is a causal risk factor for CRP and there is evidence of shared genetic regions between CRP and OP.
HUMAN MOLECULAR GENETICS
(2022)
Article
Pediatrics
Ming Hin Chung, Gilbert T. Chua, Daniel Leung, Koon Wing Chan, John Nicholls, Yu Lung Lau
Summary: X-linked lymphoproliferative disease (XLP1) is a genetic disorder causing severe immune dysregulation due to a mutation in the SH2D1A gene. A 5-year-old Nepalese boy with XLP1 and probable SARS died from diffuse alveolar damage during the SARS outbreak. Most children with COVID-19 have mild symptoms, but severe cases may be associated with underlying genetic immune disorders.
FRONTIERS IN PEDIATRICS
(2022)
Article
Genetics & Heredity
Jeffrey Fong Ting Chau, Mullin Ho Chung Yu, Martin Man Chun Chui, Cyrus Chun Wing Yeung, Aaron Wing Cheung Kwok, Xuehan Zhuang, Ryan Lee, Jasmine Lee Fong Fung, Mianne Lee, Christopher Chun Yu Mak, Nicole Ying Ting Ng, Claudia Ching Yan Chung, Marcus Chun Yin Chan, Mandy Ho Yin Tsang, Joshua Chun Ki Chan, Kelvin Yuen Kwong Chan, Anita Sik Yau Kan, Patrick Ho Yu Chung, Wanling Yang, So Lun Lee, Godfrey Chi Fung Chan, Paul Kwong Hang Tam, Yu Lung Lau, Kit San Yeung, Brian Hon Yin Chung, Clara Sze Man Tang
Summary: This study analyzed genetic sequencing data from the Southern Chinese population and found that approximately half of the population are carriers of one or more recessive genetic disorders, with a portion of carriers having treatable inherited conditions. The findings can inform carrier screening recommendations for the Southern Chinese population.
NPJ GENOMIC MEDICINE
(2022)
Article
Multidisciplinary Sciences
Wilfred Hing-Sang Wong, Daniel Leung, Gilbert T. Chua, Jaime Sou Da Rosa Duque, Sinead Peare, Hung Kwan So, Sau Man Chan, Mike Yat-Wah Kwan, Patrick Ip, Yu Lung Lau
Summary: This study presents a novel data set on Hong Kong's adolescents' attitude towards the COVID-19 vaccination, excluding their parental opinions. Using a cross-sectional questionnaire survey, the research collected 2609 surveys that fit the criteria and identified factors that affect vaccine hesitancy. The government can utilize this data to choose effective ways to promote the COVID-19 vaccination and educate the general population.
Article
Anesthesiology
Melody Kasher, Frances M. K. Williams, Maxim B. Freidin, Stacey S. Cherny, Ida Malkin, Gregory Livshits
Summary: The mechanisms underlying the relationships between chronic back pain (CBP) and other musculoskeletal (MSK) conditions are controversial and limited. This study used UK Biobank data to analyze genetic-epidemiological relationships, and found that C-reactive protein (CRP) only causally predicts CBP. Colocalization analysis identified shared genetic influences between CBP and its proposed risk factors. It is speculated that common inflammatory mechanisms contribute to CBP and its MSK comorbidities.
Article
Biochemical Research Methods
Zhenmiao Zhang, Chao Yang, Werner Pieter Veldsman, Xiaodong Fang, Lu Zhang
Summary: This paper comprehensively evaluates 19 commonly used assembly tools on metagenomic sequencing datasets from simulation, mock communities, and human gut microbiomes. It finds that long-read assemblers generate high contig contiguity but fail to reveal some medium- and high-quality metagenome-assembled genomes (MAGs). Linked-read assemblers obtain the highest number of overall near-complete MAGs from the human gut microbiomes. Hybrid assemblers using both short- and long-read sequencing are promising methods to improve both total assembly length and the number of near-complete MAGs. The paper also discusses the running time and memory consumption of these assembly tools and provides practical guidance for selecting them.
BRIEFINGS IN BIOINFORMATICS
(2023)
Article
Biochemical Research Methods
Ke Xu, ChinWang Cheong, Werner P. Veldsman, Aiping Lyu, William K. Cheung, Lu Zhang
Summary: Single-cell ribonucleic acid sequencing (scRNA-seq) is used to quantify gene expression at the transcriptomic level with single-cell resolution, but excessive missing values in scRNA-seq data impede analysis. IGSimpute is an accurate and interpretable imputation method that outperforms 12 other methods in recovering missing values in scRNA-seq data. It also has applications in denoising gene expression profiles and indicating cellular age.
BRIEFINGS IN BIOINFORMATICS
(2023)
Review
Biochemical Research Methods
Jingjing Wang, Werner Pieter Veldsman, Xiaodong Fang, Yufen Huang, Xuefeng Xie, Aiping Lyu, Lu Zhang
Summary: Genome assembly is a computational technique used to create a comprehensive and precise representation of the entire genome by piecing together DNA fragments generated by sequencing technologies. Generating a high-quality human reference genome is crucial for understanding human biology and downstream genomic variation analysis. This paper benchmarks various strategies for human genome assembly using different sequencing technologies and tools, and compares their performances in terms of continuity, accuracy, completeness, variant calling, and phasing. It recommends the use of PacBio HiFi long-reads for low base errors, Oxford Nanopore long-reads for continuous contigs (with further polishing for quality improvement), and Hi-C for chromosome-level scaffolding. Combining multiple technologies can further enhance the quality and completeness of genome assembly, and for diploid assembly, hifiasm is recommended as the best tool for human diploid genome assembly using PacBio HiFi and Hi-C data. Advances in human diploid assemblers using PacBio HiFi reads and other technologies are expected to enable high-quality, chromosome-level, and haplotype-resolved human genome assemblies in the future.
BRIEFINGS IN BIOINFORMATICS
(2023)
Article
Medicine, Research & Experimental
Stacey S. Cherny, Michal Chowers, Uri Obolski
Summary: The study found that patterns of cross-resistance to antibiotics differ across sample sources, emphasizing the importance of considering the sample source when assessing the likelihood of bacteria resistance to multiple antibiotics.
COMMUNICATIONS MEDICINE
(2023)