OTUD7A Regulates Neurodevelopmental Phenotypes in the 15q13.3 Microdeletion Syndrome
Copy-number variations (CNVs) are strong risk factors for neurodevelopmental and psychiatric disorders. The 15q13.3 microdeletion syndrome region contains up to ten genes and is associated with numerous conditions, including autism spectrum disorder (ASD), epilepsy, schizophrenia, and intellectual disability; however, the mechanisms underlying the pathogenesis of 15q13.3 microdeletion syndrome remain unknown. We combined whole-genome sequencing, human brain gene expression (proteome and transcriptome), and a mouse model with a syntenic heterozygous deletion (Df(h15q13)/+ mice) and determined that the microdeletion results ...
Source: The American Journal of Human Genetics - February 1, 2018 Category: Genetics & Stem Cells Authors: Mohammed Uddin, Brianna K. Unda, Vickie Kwan, Nicholas T. Holzapfel, Sean H. White, Leon Chalil, Marc Woodbury-Smith, Karen S. Ho, Erin Harward, Nadeem Murtaza, Biren Dave, Giovanna Pellecchia, Lia D ’Abate, Thomas Nalpathamkalam, Sylvia Lamoureux, John Tags: Article Source Type: research

This Month in The Journal
Regulation of gene expression might be the largest driving factor in normal variation in the phenotypic differences between individuals. In genome-wide association studies, for example, SNPs associated with an array of complex traits are located in regulatory regions, supporting the idea that these variants might alter transcription factor (TF) binding and gene expression. Although there is a growing interest in variation present in these regions, it remains unclear how regulatory regions evolved and acquired their function. (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - February 1, 2018 Category: Genetics & Stem Cells Authors: Sarah Ratzel, Sara B. Cullinan Tags: Editors' Corner Source Type: research

Biallelic Variants in CNPY3, Encoding an Endoplasmic Reticulum Chaperone, Cause Early-Onset Epileptic Encephalopathy
Early-onset epileptic encephalopathies, including West syndrome (WS), are a group of neurological disorders characterized by developmental impairments and intractable seizures from early infancy. We have now identified biallelic CNPY3 variants in three individuals with WS; these include compound-heterozygous missense and frameshift variants in a family with two affected siblings (individuals 1 and 2) and a homozygous splicing variant in a consanguineous family (individual 3). All three individuals showed hippocampal malrotation. (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - January 30, 2018 Category: Genetics & Stem Cells Authors: Hiroki Mutoh, Mitsuhiro Kato, Tenpei Akita, Takuma Shibata, Hiroyuki Wakamoto, Hiroko Ikeda, Hiroki Kitaura, Kazushi Aoto, Mitsuko Nakashima, Tianying Wang, Chihiro Ohba, Satoko Miyatake, Noriko Miyake, Akiyoshi Kakita, Kensuke Miyake, Atsuo Fukuda, Naomi Tags: Report Source Type: research

Assessment of the Clinical Relevance of BRCA2 Missense Variants by Functional and Computational Approaches
Many variants of uncertain significance (VUS) have been identified in BRCA2 through clinical genetic testing. VUS pose a significant clinical challenge because the contribution of these variants to cancer risk has not been determined. We conducted a comprehensive assessment of VUS in the BRCA2 C-terminal DNA binding domain (DBD) by using a validated functional assay of BRCA2 homologous recombination (HR) DNA-repair activity and defined a classifier of variant pathogenicity. Among 139 variants evaluated, 54 had ≥99% probability of pathogenicity, and 73 had ≥95% probability of neutrality. (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - January 25, 2018 Category: Genetics & Stem Cells Authors: Lucia Guidugli, Hermela Shimelis, David L. Masica, Vernon S. Pankratz, Gary B. Lipton, Namit Singh, Chunling Hu, Alvaro N.A. Monteiro, Noralane M. Lindor, David E. Goldgar, Rachel Karchin, Edwin S. Iversen, Fergus J. Couch Tags: Article Source Type: research

Functional Dysregulation of CDC42 Causes Diverse Developmental Phenotypes
Exome sequencing has markedly enhanced the discovery of genes implicated in Mendelian disorders, particularly for individuals in whom a known clinical entity could not be assigned. This has led to the recognition that phenotypic heterogeneity resulting from allelic mutations occurs more commonly than previously appreciated. Here, we report that missense variants in CDC42, a gene encoding a small GTPase functioning as an intracellular signaling node, underlie a clinically heterogeneous group of phenotypes characterized by variable growth dysregulation, facial dysmorphism, and neurodevelopmental, immunological, and hematolog...
Source: The American Journal of Human Genetics - January 25, 2018 Category: Genetics & Stem Cells Authors: Simone Martinelli, Oliver H.F. Krumbach, Francesca Pantaleoni, Simona Coppola, Ehsan Amin, Luca Pannone, Kazem Nouri, Luciapia Farina, Radovan Dvorsky, Francesca Lepri, Marcel Buchholzer, Raphael Konopatzki, Laurence Walsh, Katelyn Payne, Mary Ella Pierpo Tags: Report Source Type: research

Reccurrent F8 Intronic Deletion Found in Mild Hemophilia A Causes Alu Exonization
This study describes an original pathological mechanism by which a small intronic deletion leads to Alu exonization. We identified an intronic deletion, c.2113+461_2113+473del, in the F8 intron 13, in two individuals with mild hemophilia A. In  vivo and in vitro transcript analysis found an aberrant transcript, with an insertion of a 122-bp intronic fragment (c.2113_2114ins2113+477_2113+598) at the exon 13–14 junction. (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - January 18, 2018 Category: Genetics & Stem Cells Authors: Yohann Jourdy, Alexandre Janin, Mathilde Fretigny, Anne Lienhart, Claude N égrier, Dominique Bozon, Christine Vinciguerra Tags: Article Source Type: research

Evolutionary Rewiring of Human Regulatory Networks by Waves of Genome Expansion
Genome expansion is believed to be an important driver of the evolution of gene regulation. To investigate the role of a newly arising sequence in rewiring regulatory networks, we estimated the age of each region of the human genome by applying maximum parsimony to genome-wide alignments with 100 vertebrates. We then studied the age distribution of several types of functional regions, with a focus on regulatory elements. The age distribution of regulatory elements reveals the extensive use of newly formed genomic sequence in the evolution of regulatory interactions. (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - January 18, 2018 Category: Genetics & Stem Cells Authors: Davide Marnetto, Federica Mantica, Ivan Molineris, Elena Grassi, Igor Pesando, Paolo Provero Tags: Article Source Type: research

Loss of GPNMB Causes Autosomal-Recessive Amyloidosis Cutis Dyschromica in Humans
We report here that the compound heterozygosity or homozygosity of GPNMB truncating alleles is the cause of autosomal-recessive ACD. (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - January 11, 2018 Category: Genetics & Stem Cells Authors: Chi-Fan Yang, Shuan-Pei Lin, Chien-Ping Chiang, Yu-Hung Wu, Weng Siong H ’ng, Chun-Ping Chang, Yuan-Tsong Chen, Jer-Yuarn Wu Tags: Article Source Type: research

The Expanding Landscape of Alternative Splicing Variation in Human Populations
Alternative splicing is a tightly regulated biological process by which the number of gene products for any given gene can be greatly expanded. Genomic variants in splicing regulatory sequences can disrupt splicing and cause disease. Recent developments in sequencing technologies and computational biology have allowed researchers to investigate alternative splicing at an unprecedented scale and resolution. Population-scale transcriptome studies have revealed many naturally occurring genetic variants that modulate alternative splicing and consequently influence phenotypic variability and disease susceptibility in human popu...
Source: The American Journal of Human Genetics - January 4, 2018 Category: Genetics & Stem Cells Authors: Eddie Park, Zhicheng Pan, Zijun Zhang, Lan Lin, Yi Xing Tags: Review Source Type: research

This Month in The Journal
Robinow syndrome, a rare skeletal dysplasia, has proven an especially difficult disorder to diagnose molecularly. Much of this challenge stems from locus heterogeneity that leads to an incomplete understanding of disease pathomechanism. In this issue, White et  al. use a combination of whole-exome and Sanger sequencing to explore the genetic cause of clinically suspected Robinow syndrome in over 20 individuals. The authors identify causative mutations in NXN and FZD2 in addition to those in previously reported genes DVL1, DVL3, and WNT5A. (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - January 4, 2018 Category: Genetics & Stem Cells Authors: Sarah Ratzel, Sara B. Cullinan Tags: Editors' Corner Source Type: research

The Comoros Show the Earliest Austronesian Gene Flow into the Swahili Corridor
At the dawn of the second millennium, the expansion of the Indian Ocean trading network aligned with the emergence of an outward-oriented community along the East African coast to create a cosmopolitan cultural and trading zone known as the Swahili Corridor. On the basis of analyses of new genome-wide genotyping data and uniparental data in 276 individuals from coastal Kenya and the Comoros islands, along with large-scale genetic datasets from the Indian Ocean rim, we reconstruct historical population dynamics to show that the Swahili Corridor is largely an eastern Bantu genetic continuum. (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - January 4, 2018 Category: Genetics & Stem Cells Authors: Nicolas Brucato, Veronica Fernandes, St éphane Mazières, Pradiptajati Kusuma, Murray P. Cox, Joseph Wainaina Ng’ang’a, Mohammed Omar, Marie-Claude Simeone-Senelle, Coralie Frassati, Farida Alshamali, Bertrand Fin, Anne Boland, Jean-Francois Deleuze, Tags: Article Source Type: research

HIPAA ’s Individual Right of Access to Genomic Data: Reconciling Safety and Civil Rights
In 2014, the United States granted individuals a right of access to their own laboratory test results, including genomic data. Many observers feel that this right is in tension with regulatory and bioethical standards designed to protect the safety of people who undergo genomic testing. This commentary attributes this tension to growing pains within an expanding federal regulatory program for genetic and genomic testing. The Genetic Information Nondiscrimination Act of 2008 expanded the regulatory agenda to encompass civil rights and consumer safety. (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - January 4, 2018 Category: Genetics & Stem Cells Authors: Barbara J. Evans Tags: Commentary Source Type: research

Life-Course Genome-wide Association Study Meta-analysis of Total Body BMD and Assessment of Age-Specific Effects
Bone mineral density (BMD) assessed by DXA is used to evaluate bone health. In children, total body (TB) measurements are commonly used; in older individuals, BMD at the lumbar spine (LS) and femoral neck (FN) is used to diagnose osteoporosis. To date, genetic variants in more than 60 loci have been identified as associated with BMD. To investigate the genetic determinants of TB-BMD variation along the life course and test for age-specific effects, we performed a meta-analysis of 30 genome-wide association studies (GWASs) of TB-BMD including 66,628 individuals overall and divided across five age strata, each spanning 15 ye...
Source: The American Journal of Human Genetics - January 4, 2018 Category: Genetics & Stem Cells Authors: Carolina Medina-Gomez, John P. Kemp, Katerina Trajanoska, Jian ’an Luan, Alessandra Chesi, Tarunveer S. Ahluwalia, Dennis O. Mook-Kanamori, Annelies Ham, Fernando P. Hartwig, Daniel S. Evans, Raimo Joro, Ivana Nedeljkovic, Hou-Feng Zheng, Kun Zhu, Musta Tags: Article Source Type: research

Rare Coding Variants in ANGPTL6 Are Associated with Familial Forms of Intracranial Aneurysm
Intracranial aneurysms (IAs) are acquired cerebrovascular abnormalities characterized by localized dilation and wall thinning in intracranial arteries, possibly leading to subarachnoid hemorrhage and severe outcome in case of rupture. Here, we identified one rare nonsense variant (c.1378A>T) in the last exon of ANGPTL6 (Angiopoietin-Like 6) —which encodes a circulating pro-angiogenic factor mainly secreted from the liver—shared by the four tested affected members of a large pedigree with multiple IA-affected case subjects. (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - January 4, 2018 Category: Genetics & Stem Cells Authors: Romain Bourcier, Solena Le Scouarnec, St éphanie Bonnaud, Matilde Karakachoff, Emmanuelle Bourcereau, Sandrine Heurtebise-Chrétien, Céline Menguy, Christian Dina, Floriane Simonet, Alexis Moles, Cédric Lenoble, Pierre Lindenbaum, Stéphanie Chatel, Be Tags: Article Source Type: research

A Comprehensive Workflow for Read Depth-Based Identification of Copy-Number Variation from Whole-Genome Sequence Data
A remaining hurdle to whole-genome sequencing (WGS) becoming a first-tier genetic test has been accurate detection of copy-number variations (CNVs). Here, we used several datasets to empirically develop a detailed workflow for identifying germline CNVs>1 kb from  short-read WGS data using read depth-based algorithms. Our workflow is comprehensive in that it addresses all stages of the CNV-detection process, including DNA library preparation, sequencing, quality control, reference mapping, and computational CNV identification. (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - January 4, 2018 Category: Genetics & Stem Cells Authors: Brett Trost, Susan Walker, Zhuozhi Wang, Bhooma Thiruvahindrapuram, Jeffrey R. MacDonald, Wilson W.L. Sung, Sergio L. Pereira, Joe Whitney, Ada J.S. Chan, Giovanna Pellecchia, Miriam S. Reuter, Si Lok, Ryan K.C. Yuen, Christian R. Marshall, Daniele Merico Tags: Article Source Type: research

Genomic DNA Methylation Signatures Enable Concurrent Diagnosis and Clinical Genetic Variant Classification in Neurodevelopmental Syndromes
Pediatric developmental syndromes present with systemic, complex, and often overlapping clinical features that are not infrequently a consequence of Mendelian inheritance of mutations in genes involved in DNA methylation, establishment of histone modifications, and chromatin remodeling (the “epigenetic machinery”). The mechanistic cross-talk between histone modification and DNA methylation suggests that these syndromes might be expected to display specific DNA methylation signatures that are a reflection of those primary errors associated with chromatin dysregulation. (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - January 4, 2018 Category: Genetics & Stem Cells Authors: Erfan Aref-Eshghi, David I. Rodenhiser, Laila C. Schenkel, Hanxin Lin, Cindy Skinner, Peter Ainsworth, Guillaume Par é, Rebecca L. Hood, Dennis E. Bulman, Kristin D. Kernohan, Care4Rare Canada Consortium, Kym M. Boycott, Philippe M. Campeau, Charles Schw Tags: Article Source Type: research

Biallelic Mutations in FUT8 Cause a Congenital Disorder of Glycosylation with Defective Fucosylation
Fucosyltransferase 8 (FUT8) encodes a Golgi-localized α1,6 fucosyltransferase that is essential for transferring the monosaccharide fucose into N-linked glycoproteins, a process known as “core fucosylation.” Here we describe three unrelated individuals, who presented with intrauterine growth retardation, severe developmental and growth delays with shortened limbs, neurological impairments, and respiratory complications. Each underwent whole-exome sequencing and was found to carry pathogenic variants in FUT8. (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - January 4, 2018 Category: Genetics & Stem Cells Authors: Bobby G. Ng, Gege Xu, Nandini Chandy, Joan Steyermark, Deepali N. Shinde, Kelly Radtke, Kimiyo Raymond, Carlito B. Lebrilla, Ali AlAsmari, Sharon F. Suchy, Z öe Powis, Eissa Ali Faqeih, Susan A. Berry, David F. Kronn, Hudson H. Freeze Tags: Report Source Type: research

Transitions in an Era of Disruptive Change
I attended my first American Society of Human Genetics meeting, the 25th anniversary meeting, in Atlanta, GA in  1973. I was an undergraduate presenting a study of chromosome banding I helped to complete as a summer student at a community hospital near where I grew up. I had been exposed to genetics a couple of summers before, as a high school junior working in a program sponsored by the National Science Fo undation. My interests at that time were evolving toward medicine, but this experience exposed me to scientific research. (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - January 4, 2018 Category: Genetics & Stem Cells Authors: Bruce R. Korf Tags: Editors' Corner Source Type: research

De Novo Missense Mutations in DHX30 Impair Global Translation and Cause a Neurodevelopmental Disorder
(The American Journal of Human Genetics 101, 716 –724; November 2, 2017) (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - January 4, 2018 Category: Genetics & Stem Cells Authors: Davor Lessel, Claudia Schob, S ébastien Küry, Margot R.F. Reijnders, Tamar Harel, Mohammad K. Eldomery, Zeynep Coban-Akdemir, Jonas Denecke, Shimon Edvardson, Estelle Colin, Alexander P.A. Stegmann, Erica H. Gerkes, Marine Tessarech, Dominique Bonneau, Tags: Correction Source Type: research

Genotype-Phenotype Correlation in NF1: Evidence for a More Severe Phenotype Associated with Missense Mutations Affecting NF1 Codons 844 –848
Neurofibromatosis type 1 (NF1), a common genetic disorder with a birth incidence of 1:2,000 –3,000, is characterized by a highly variable clinical presentation. To date, only two clinically relevant intragenic genotype-phenotype correlations have been reported for NF1 missense mutations affecting p.Arg1809 and a single amino acid deletion p.Met922del. Both variants predispose to a distin ct mild NF1 phenotype with neither externally visible cutaneous/plexiform neurofibromas nor other tumors. Here, we report 162 individuals (129 unrelated probands and 33 affected relatives) heterozygous for a constitutional missense m...
Source: The American Journal of Human Genetics - December 28, 2017 Category: Genetics & Stem Cells Authors: Magdalena Koczkowska, Yunjia Chen, Tom Callens, Alicia Gomes, Angela Sharp, Sherrell Johnson, Meng-Chang Hsiao, Zhenbin Chen, Meena Balasubramanian, Christopher P. Barnett, Troy A. Becker, Shay Ben-Shachar, Debora R. Bertola, Jaishri O. Blakeley, Emma M.M Tags: Article Source Type: research

KIAA1109 Variants Are Associated with a Severe Disorder of Brain Development and Arthrogryposis
Whole-exome and targeted sequencing of 13 individuals from 10 unrelated families with overlapping clinical manifestations identified loss-of-function and missense variants in KIAA1109 allowing delineation of an autosomal-recessive multi-system syndrome, which we suggest to name Alkuraya-Ku činskas syndrome (MIM 617822). Shared phenotypic features representing the cardinal characteristics of this syndrome combine brain atrophy with clubfoot and arthrogryposis. Affected individuals present with cerebral parenchymal underdevelopment, ranging from major cerebral parenchymal thinning with lissencephalic aspect to moderate pare...
Source: The American Journal of Human Genetics - December 28, 2017 Category: Genetics & Stem Cells Authors: Lucie Gueneau, Richard J. Fish, Hanan E. Shamseldin, Norine Voisin, Fr édéric Tran Mau-Them, Egle Preiksaitiene, Glen R. Monroe, Angeline Lai, Audrey Putoux, Fabienne Allias, Qamariya Ambusaidi, Laima Ambrozaityte, Loreta Cimbalistienė, Julien Delafont Tags: Article Source Type: research

Genome-wide Study of Atrial Fibrillation Identifies Seven Risk Loci and Highlights Biological Pathways and Regulatory Elements Involved in Cardiac Development
Atrial fibrillation (AF) is a common cardiac arrhythmia and a major risk factor for stroke, heart failure, and premature death. The pathogenesis of AF remains poorly understood, which contributes to the current lack of highly effective treatments. To understand the genetic variation and biology underlying AF, we undertook a genome-wide association study (GWAS) of 6,337 AF individuals and 61,607 AF-free individuals from Norway, including replication in an additional 30,679 AF individuals and 278,895 AF-free individuals. (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - December 28, 2017 Category: Genetics & Stem Cells Authors: Jonas B. Nielsen, Lars G. Fritsche, Wei Zhou, Tanya M. Teslovich, Oddgeir L. Holmen, Stefan Gustafsson, Maiken E. Gabrielsen, Ellen M. Schmidt, Robin Beaumont, Brooke N. Wolford, Maoxuan Lin, Chad M. Brummett, Michael H. Preuss, Lena Refsgaard, Erwin P. B Tags: Article Source Type: research

WNT Signaling Perturbations Underlie the Genetic Heterogeneity of Robinow Syndrome
Locus heterogeneity characterizes a variety of skeletal dysplasias often due to interacting or overlapping signaling pathways. Robinow syndrome is a skeletal disorder historically refractory to molecular diagnosis, potentially stemming from substantial genetic heterogeneity. All current known pathogenic variants reside in genes within the noncanonical Wnt signaling pathway including ROR2, WNT5A, and more recently, DVL1 and DVL3. However, ∼70% of autosomal-dominant Robinow syndrome cases remain molecularly unsolved. (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - December 21, 2017 Category: Genetics & Stem Cells Authors: Janson J. White, Juliana F. Mazzeu, Zeynep Coban-Akdemir, Yavuz Bayram, Vahid Bahrambeigi, Alexander Hoischen, Bregje W.M. van Bon, Alper Gezdirici, Elif Yilmaz Gulec, Francis Ramond, Renaud Touraine, Julien Thevenon, Marwan Shinawi, Erin Beaver, Jennifer Tags: Article Source Type: research

Missense Variants in RHOBTB2 Cause a Developmental and Epileptic Encephalopathy in Humans, and Altered Levels Cause Neurological Defects in Drosophila
Although the role of typical Rho GTPases and other Rho-linked proteins in synaptic plasticity and cognitive function and dysfunction is widely acknowledged, the role of atypical Rho GTPases (such as RHOBTB2) in neurodevelopment has barely been characterized. We have now identified de novo missense variants clustering in the BTB-domain-encoding region of RHOBTB2 in ten individuals with a similar phenotype, including early-onset epilepsy, severe intellectual disability, postnatal microcephaly, and movement disorders. (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - December 21, 2017 Category: Genetics & Stem Cells Authors: Jonas Straub, Enrico D.H. Konrad, Johanna Gr üner, Annick Toutain, Levinus A. Bok, Megan T. Cho, Heather P. Crawford, Holly Dubbs, Ganka Douglas, Rebekah Jobling, Diana Johnson, Bryan Krock, Mohamad A. Mikati, Addie Nesbitt, Joost Nicolai, Meredith Phill Tags: Article Source Type: research

Histone Lysine Methylases and Demethylases in the Landscape of Human Developmental Disorders
Histone lysine methyltransferases (KMTs) and demethylases (KDMs) underpin gene regulation. Here we demonstrate that variants causing haploinsufficiency of KMTs and KDMs are frequently encountered in individuals with developmental disorders. Using a combination of human variation databases and existing animal models, we determine 22 KMTs and KDMs as additional candidates for dominantly inherited developmental disorders. We show that KMTs and KDMs that are associated with, or are candidates for, dominant developmental disorders tend to have a higher level of transcription, longer canonical transcripts, more interactors, and ...
Source: The American Journal of Human Genetics - December 21, 2017 Category: Genetics & Stem Cells Authors: V íctor Faundes, William G. Newman, Laura Bernardini, Natalie Canham, Jill Clayton-Smith, Bruno Dallapiccola, Sally J. Davies, Michelle K. Demos, Amy Goldman, Harinder Gill, Rachel Horton, Bronwyn Kerr, Dhavendra Kumar, Anna Lehman, Shane McKee, Jenny Mo Tags: Report Source Type: research

Penetrance of Polygenic Obesity Susceptibility Loci across the Body Mass Index Distribution
A growing number of single-nucleotide polymorphisms (SNPs) have been associated with body mass index (BMI) and obesity, but whether the effects of these obesity-susceptibility loci are uniform across the BMI distribution remains unclear. We studied the effects of 37 BMI-associated SNPs in 75,230 adults of European ancestry across BMI percentiles by using conditional quantile regression (CQR) and meta-regression (MR) models. The effects of nine SNPs (24%) —rs1421085 (FTO; p = 8.69 × 10−15), rs6235 (PCSK1; p = 7.11 × 10−6), rs7903146 (TCF7L2; p = 9.60 × 10−6)...
Source: The American Journal of Human Genetics - December 7, 2017 Category: Genetics & Stem Cells Authors: Arkan Abadi, Akram Alyass, Sebastien Robiou du Pont, Ben Bolker, Pardeep Singh, Viswanathan Mohan, Rafael Diaz, James C. Engert, Salim Yusuf, Hertzel C. Gerstein, Sonia S. Anand, David Meyre Tags: Article Source Type: research

A Powerful Approach to Estimating Annotation-Stratified Genetic Covariance via GWAS Summary Statistics
Despite the success of large-scale genome-wide association studies (GWASs) on complex traits, our understanding of their genetic architecture is far from complete. Jointly modeling multiple traits ’ genetic profiles has provided insights into the shared genetic basis of many complex traits. However, large-scale inference sets a high bar for both statistical power and biological interpretability. Here we introduce a principled framework to estimate annotation-stratified genetic covariance be tween traits using GWAS summary statistics. (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - December 7, 2017 Category: Genetics & Stem Cells Authors: Qiongshi Lu, Boyang Li, Derek Ou, Margret Erlendsdottir, Ryan L. Powles, Tony Jiang, Yiming Hu, David Chang, Chentian Jin, Wei Dai, Qidu He, Zefeng Liu, Shubhabrata Mukherjee, Paul K. Crane, Hongyu Zhao Tags: Article Source Type: research

Exome-wide Association Study Identifies GREB1L Mutations in Congenital Kidney Malformations
(The American Journal of Human Genetics 101, 789 –802; November 2, 2017) (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - December 7, 2017 Category: Genetics & Stem Cells Authors: Simone Sanna-Cherchi, Kamal Khan, Rik Westland, Priya Krithivasan, Lorraine Fievet, Hila Milo Rasouly, Iuliana Ionita-Laza, Valentina P. Capone, David A. Fasel, Krzysztof Kiryluk, Sitharthan Kamalakaran, Monica Bodria, Edgar A. Otto, Matthew G. Sampson, C Tags: Correction Source Type: research

De Novo Variants in GRIA4 Lead to Intellectual Disability with or without Seizures and Gait Abnormalities
Using trio whole-exome sequencing, we have identified de novo heterozygous pathogenic variants in GRIA4 in five unrelated individuals with intellectual disability and other symptoms. GRIA4 encodes an AMPA receptor subunit known as GluR4, which is found on excitatory glutamatergic synapses and is important for learning and memory. Four of the variants are located in the highly conserved SYTANLAAF motif in the transmembrane protein M3, and the fifth is in an extra-cellular domain. Molecular modeling of the altered protein showed that three of the variants in the SYTANLAAF motif orient toward the center of the pore region and...
Source: The American Journal of Human Genetics - December 7, 2017 Category: Genetics & Stem Cells Authors: Sonja Martin, Adam Chamberlin, Deepali N. Shinde, Maja Hempel, Tim M. Strom, Allison Schreiber, Jessika Johannsen, Lilian Bomme Ousager, Martin J. Larsen, Lars Kjaersgaard Hansen, Ali Fatemi, Julie S. Cohen, Johannes Lemke, Kristina P. S ørensen, Katheri Tags: Report Source Type: research

This Month in Genetics
The infantile form of spinal muscular atrophy (SMA) is a devastating condition with a median life expectancy of 2  years without ventilation. Essentially, no effective interventions have been available, but in a recent issue of The New England Journal of Medicine, back-to-back publications report clinical trials of two completely different therapies that both show promise for treating SMA. Mendell et al. repo rt the use of single-dose intravenous gene therapy for infants with SMA, whereas Finkel et al. (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - December 7, 2017 Category: Genetics & Stem Cells Authors: Kathryn B. Garber Tags: Editors' Corner Source Type: research

ACTB Loss-of-Function Mutations Result in a Pleiotropic Developmental Disorder
We describe heterozygous ACTB deletions and nonsense and frameshift mutations in 33 individuals with developmental delay, apparent intellectual disability, increased frequency of internal organ malformations (including t hose of the heart and the renal tract), growth retardation, and a recognizable facial gestalt (interrupted wavy eyebrows, dense eyelashes, wide nose, wide mouth, and a prominent chin) that is distinct from characteristics of individuals with BRWS. (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - December 7, 2017 Category: Genetics & Stem Cells Authors: Sara Cuvertino, Helen M. Stuart, Kate E. Chandler, Neil A. Roberts, Ruth Armstrong, Laura Bernardini, Sanjeev Bhaskar, Bert Callewaert, Jill Clayton-Smith, Cristina Hernando Davalillo, Charu Deshpande, Koenraad Devriendt, Maria C. Digilio, Abhijit Dixit, Tags: Report Source Type: research

Allelic Expression Imbalance Promoting a Mutant PEX6 Allele Causes Zellweger Spectrum Disorder
Zellweger spectrum disorders (ZSDs) are autosomal-recessive disorders that are caused by defects in peroxisome biogenesis due to bi-allelic mutations in any of 13 different PEX genes. Here, we identified seven unrelated individuals affected with an apparent dominant ZSD in whom a heterozygous mutant PEX6 allele (c.2578C>T [p.Arg860Trp]) was overrepresented due to allelic expression imbalance (AEI). We demonstrated that AEI of PEX6 is a common phenomenon and is correlated with heterozygosity for a frequent variant in the 3 ′ untranslated region (UTR) of the mutant allele, which disrupts the most distal of two polya...
Source: The American Journal of Human Genetics - December 7, 2017 Category: Genetics & Stem Cells Authors: Kim D. Falkenberg, Nancy E. Braverman, Ann B. Moser, Steven J. Steinberg, Femke C.C. Klouwer, Agatha Schl üter, Montserrat Ruiz, Aurora Pujol, Martin Engvall, Karin Naess, FrancJan van Spronsen, Irene Körver-Keularts, M. Estela Rubio-Gozalbo, Sacha Ferd Tags: Article Source Type: research

This Month in The Journal
Copy-number variants (CNVs) of chromosomal region 15q13.3 are associated with a broad neuropsychiatric condition that includes intellectual disability, developmental delay, epilepsy, autism spectrum disorder, and schizophrenia. Several studies narrowing the critical region have suggested that the phenotype appears to be driven largely by CHRNA7, encoding the α7 nicotinic acetylcholine receptor (α7 nAChR), and that duplications result in a milder phenotype than deletions. However, the mechanism underlying the pathogenicity is unclear. (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - December 7, 2017 Category: Genetics & Stem Cells Authors: Sarah Ratzel, Sara B. Cullinan Tags: Editors' Corner Source Type: research

So Long, and Thanks for All the Genes!
Reflecting on the past 6 years as editor of The American Journal of Human Genetics, I, like previous editors,1 –4 feel immense gratitude for the privilege of the position. It is truly an honor to have been entrusted by the American Society of Human Genetics (ASHG) with the helm of this highly respected vessel. Of course, The Journal long ago became too big to sail single handedly, and I was fortunate to be joined on this journey by a superb crew. Deputy Editor Sara Cullinan, who has been with me from the start, brought experience in publishing and a keen sensibility for navigating the ever-changing scientific wa...
Source: The American Journal of Human Genetics - December 7, 2017 Category: Genetics & Stem Cells Authors: David L. Nelson Tags: Editors' Corner Source Type: research

A Selection Operator for Summary Association Statistics Reveals Allelic Heterogeneity of Complex Traits
In recent years, as a secondary analysis in genome-wide association studies (GWASs), conditional and joint multiple-SNP analysis (GCTA-COJO) has been successful in allowing the discovery of additional association signals within detected loci. This suggests that many loci mapped in GWASs harbor more than a single causal variant. In order to interpret the underlying mechanism regulating a complex trait of interest in each discovered locus, researchers must assess the magnitude of allelic heterogeneity within the locus. (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - November 30, 2017 Category: Genetics & Stem Cells Authors: Zheng Ning, Youngjo Lee, Peter K. Joshi, James F. Wilson, Yudi Pawitan, Xia Shen Tags: Article Source Type: research

DNA Methylation Analysis Identifies Loci for Blood Pressure Regulation
Genome-wide association studies have identified hundreds of genetic variants associated with blood pressure (BP), but sequence variation accounts for a small fraction of the phenotypic variance. Epigenetic changes may alter the expression of genes involved in BP regulation and explain part of the missing heritability. We therefore conducted a two-stage meta-analysis of the cross-sectional associations of systolic and diastolic BP with blood-derived genome-wide DNA methylation measured on the Infinium HumanMethylation450 BeadChip in 17,010 individuals of European, African American, and Hispanic ancestry. (Source: The Americ...
Source: The American Journal of Human Genetics - November 30, 2017 Category: Genetics & Stem Cells Authors: Melissa A. Richard, Tianxiao Huan, Symen Ligthart, Rahul Gondalia, Min A. Jhun, Jennifer A. Brody, Marguerite R. Irvin, Riccardo Marioni, Jincheng Shen, Pei-Chien Tsai, May E. Montasser, Yucheng Jia, Catriona Syme, Elias L. Salfati, Eric Boerwinkle, Weihu Tags: Article Source Type: research

Multiethnic GWAS Reveals Polygenic Architecture of Earlobe Attachment
The genetic basis of earlobe attachment has been a matter of debate since the early 20th century, such that geneticists argue both for and against polygenic inheritance. Recent genetic studies have identified a few loci associated with the trait, but large-scale analyses are still lacking. Here, we performed a genome-wide association study of lobe attachment in a multiethnic sample of 74,660 individuals from four cohorts (three with the trait scored by an expert rater and one with the trait self-reported). (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - November 30, 2017 Category: Genetics & Stem Cells Authors: John R. Shaffer, Jinxi Li, Myoung Keun Lee, Jasmien Roosenboom, Ekaterina Orlova, Kaustabh Adhikari, 23andMe Research Team, Carla Gallo, Giovanni Poletti, Lavinia Schuler-Faccini, Maria-C átira Bortolini, Samuel Canizales-Quinteros, Francisco Rothhammer, Tags: Article Source Type: research

Monoallelic BMP2 Variants Predicted to Result in Haploinsufficiency Cause Craniofacial, Skeletal, and Cardiac Features Overlapping Those of 20p12 Deletions
Bone morphogenetic protein 2 (BMP2) in chromosomal region 20p12 belongs to a gene superfamily encoding TGF- β-signaling proteins involved in bone and cartilage biology. Monoallelic deletions of 20p12 are variably associated with cleft palate, short stature, and developmental delay. Here, we report a cranioskeletal phenotype due to monoallelic truncating and frameshift BMP2 variants and deletions in 12 in dividuals from eight unrelated families that share features of short stature, a recognizable craniofacial gestalt, skeletal anomalies, and congenital heart disease. (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - November 30, 2017 Category: Genetics & Stem Cells Authors: Tiong Yang Tan, Claudia Gonzaga-Jauregui, Elizabeth J. Bhoj, Kevin A. Strauss, Karlla Brigatti, Erik Puffenberger, Dong Li, LiQin Xie, Nanditha Das, Ioanna Skubas, Ron A. Deckelbaum, Virginia Hughes, Susannah Brydges, Sarah Hatsell, Chia-Jen Siao, Melissa Tags: Report Source Type: research

A Recurrent De Novo Nonsense Variant in ZSWIM6 Results in Severe Intellectual Disability without Frontonasal or Limb Malformations
We present detailed phenotypic information on seven unrelated individuals with a recurrent de novo nonsense variant (c.2737C>T [p.Arg913Ter]) in the penultimate exon of ZSWIM6 who have severe-profound intellectual disability and additional central and peripheral nervous system symptoms but an absence of frontonasal or limb malformations. (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - November 30, 2017 Category: Genetics & Stem Cells Authors: Elizabeth E. Palmer, Raman Kumar, Christopher T. Gordon, Marie Shaw, Laurence Hubert, Renee Carroll, Marl ène Rio, Lucinda Murray, Melanie Leffler, Tracy Dudding-Byth, Myriam Oufadem, Seema R. Lalani, Andrea M. Lewis, Fan Xia, Allison Tam, Richard Webste Tags: Report Source Type: research

Mutations in TUBB4B Cause a Distinctive Sensorineural Disease
Leber congenital amaurosis (LCA) is a neurodegenerative disease of photoreceptor cells that causes blindness within the first year of life. It occasionally occurs in syndromic metabolic diseases and plurisystemic ciliopathies. Using exome sequencing in a multiplex family and three simplex case subjects with an atypical association of LCA with early-onset hearing loss, we identified two heterozygous mutations affecting Arg391 in β-tubulin 4B isotype-encoding (TUBB4B). Inspection of the atomic structure of the microtubule (MT) protofilament reveals that the β-tubulin Arg391 residue contributes to a binding pocket t...
Source: The American Journal of Human Genetics - November 30, 2017 Category: Genetics & Stem Cells Authors: Romain Luscan, Sabrina Mechaussier, Antoine Paul, Guoling Tian, Xavier G érard, Sabine Defoort-Dellhemmes, Natalie Loundon, Isabelle Audo, Sophie Bonnin, Jean-François LeGargasson, Julien Dumont, Nicolas Goudin, Meriem Garfa-Traoré, Marc Bras, Aurore P Tags: Report Source Type: research

Functional Consequences of CHRNA7 Copy-Number Alterations in Induced Pluripotent Stem Cells and Neural Progenitor Cells
Copy-number variants (CNVs) of chromosome 15q13.3 manifest clinically as neuropsychiatric disorders with variable expressivity. CHRNA7, encoding for the α7 nicotinic acetylcholine receptor (nAChR), has been suggested as a candidate gene for the phenotypes observed. Here, we used induced pluripotent stem cells (iPSCs) and neural progenitor cells (NPCs) derived from individuals with heterozygous 15q13.3 deletions and heterozygous 15q13.3 duplications to investigate the CHRNA7-dependent molecular consequences of the respective CNVs. (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - November 9, 2017 Category: Genetics & Stem Cells Authors: Madelyn A. Gillentine, Jiani Yin, Aleksandar Bajic, Ping Zhang, Steven Cummock, Jean J. Kim, Christian P. Schaaf Tags: Article Source Type: research

The Genetic Legacy of the Indian Ocean Slave Trade: Recent Admixture and Post-admixture Selection in the Makranis of Pakistan
From the eighth century onward, the Indian Ocean was the scene of extensive trade of sub-Saharan African slaves via sea routes controlled by Muslim Arab and Swahili traders. Several populations in present-day Pakistan and India are thought to be the descendants of such slaves, yet their history of admixture and natural selection remains largely undefined. Here, we studied the genome-wide diversity of the African-descent Makranis, who reside on the Arabian Sea coast of Pakistan, as well that of four neighboring Pakistani populations, to investigate the genetic legacy, population dynamics, and tempo of the Indian Ocean slave...
Source: The American Journal of Human Genetics - November 9, 2017 Category: Genetics & Stem Cells Authors: Romuald Laso-Jadart, Christine Harmant, H élène Quach, Nora Zidane, Chris Tyler-Smith, Qasim Mehdi, Qasim Ayub, Lluis Quintana-Murci, Etienne Patin Tags: Report Source Type: research

High Rate of Recurrent De Novo Mutations in Developmental and Epileptic Encephalopathies
Developmental and epileptic encephalopathy (DEE) is a group of conditions characterized by the co-occurrence of epilepsy and intellectual disability (ID), typically with developmental plateauing or regression associated with frequent epileptiform activity. The cause of DEE remains unknown in the majority of cases. We performed whole-genome sequencing (WGS) in 197 individuals with unexplained DEE and pharmaco-resistant seizures and in their unaffected parents. We focused our attention on de novo mutations (DNMs) and identified candidate genes containing such variants. (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - November 2, 2017 Category: Genetics & Stem Cells Authors: Fadi F. Hamdan, Candace T. Myers, Patrick Cossette, Philippe Lemay, Dan Spiegelman, Alexandre Dionne Laporte, Christina Nassif, Ousmane Diallo, Jean Monlong, Maxime Cadieux-Dion, Sylvia Dobrzeniecka, Caroline Meloche, Kyle Retterer, Megan T. Cho, Jill A. Tags: Article Source Type: research

Profiling of Short-Tandem-Repeat Disease Alleles in 12,632 Human Whole Genomes
Short tandem repeats (STRs) are hyper-mutable sequences in the human genome. They are often used in forensics and population genetics and are also the underlying cause of many genetic diseases. There are challenges associated with accurately determining the length polymorphism of STR loci in the genome by next-generation sequencing (NGS). In particular, accurate detection of pathological STR expansion is limited by the sequence read length during whole-genome analysis. We developed TREDPARSE, a software package that incorporates various cues from read alignment and paired-end distance distribution, as well as a sequence st...
Source: The American Journal of Human Genetics - November 2, 2017 Category: Genetics & Stem Cells Authors: Haibao Tang, Ewen F. Kirkness, Christoph Lippert, William H. Biggs, Martin Fabani, Ernesto Guzman, Smriti Ramakrishnan, Victor Lavrenko, Boyko Kakaradov, Claire Hou, Barry Hicks, David Heckerman, Franz J. Och, C. Thomas Caskey, J. Craig Venter, Amalio Tel Tags: Article Source Type: research

De Novo Missense Mutations in DHX30 Impair Global Translation and Cause a Neurodevelopmental Disorder
DHX30 is a member of the family of DExH-box helicases, which use ATP hydrolysis to unwind RNA secondary structures. Here we identified six different de novo missense mutations in DHX30 in twelve unrelated individuals affected by global developmental delay (GDD), intellectual disability (ID), severe speech impairment and gait abnormalities. While four mutations are recurrent, two are unique with one affecting the codon of one recurrent mutation. All amino acid changes are located within highly conserved helicase motifs and were found to either impair ATPase activity or RNA recognition in different in  vitro assays. (So...
Source: The American Journal of Human Genetics - November 2, 2017 Category: Genetics & Stem Cells Authors: Davor Lessel, Claudia Schob, S ébastien Küry, Margot R.F. Reinders, Tamar Harel, Mohammad K. Eldomery, Zeynep Coban-Akdemir, Jonas Denecke, Shimon Edvardson, Estelle Colin, Alexander P.A. Stegmann, Erica H. Gerkes, Marine Tessarech, Dominique Bonneau, M Tags: Article Source Type: research

De Novo Mutations in SLC25A24 Cause a Craniosynostosis Syndrome with Hypertrichosis, Progeroid Appearance, and Mitochondrial Dysfunction
Gorlin-Chaudhry-Moss syndrome (GCMS) is a dysmorphic syndrome characterized by coronal craniosynostosis and severe midface hypoplasia, body and facial hypertrichosis, microphthalmia, short stature, and short distal phalanges. Variable lipoatrophy and cutis laxa are the basis for a progeroid appearance. Using exome and genome sequencing, we identified the recurrent de novo mutations c.650G>A (p.Arg217His) and c.649C>T (p.Arg217Cys) in SLC25A24 in five unrelated girls diagnosed with GCMS. Two of the girls had pronounced neonatal progeroid features and were initially diagnosed with Wiedemann-Rautenstrauch syndrome. (Sou...
Source: The American Journal of Human Genetics - November 2, 2017 Category: Genetics & Stem Cells Authors: Nadja Ehmke, Luitgard Graul-Neumann, Lukasz Smorag, Rainer Koenig, Lara Segebrecht, Pilar Magoulas, Fernando Scaglia, Esra Kilic, Anna F. Hennig, Nicolai Adolphs, Namrata Saha, Beatrix Fauler, Vera M. Kalscheuer, Friederike Hennig, Janine Altm üller, Chr Tags: Report Source Type: research

De Novo Mutations in SLC25A24 Cause a Disorder Characterized by Early Aging, Bone Dysplasia, Characteristic Face, and Early Demise
A series of simplex cases have been reported under various diagnoses sharing early aging, especially evident in congenitally decreased subcutaneous fat tissue and sparse hair, bone dysplasia of the skull and fingers, a distinctive facial gestalt, and prenatal and postnatal growth retardation. For historical reasons, we suggest naming the entity Fontaine syndrome. Exome sequencing of four unrelated affected individuals showed that all carried the de novo missense variant c.649C>T (p.Arg217Cys) or c.650G>A (p.Arg217His) in SLC25A24, a solute carrier 25 family member coding for calcium-binding mitochondrial carrier prot...
Source: The American Journal of Human Genetics - November 2, 2017 Category: Genetics & Stem Cells Authors: Karin Writzl, Ales Maver, Lidija Kova čič, Paula Martinez-Valero, Laura Contreras, Jorgina Satrustegui, Marco Castori, Laurence Faivre, Pablo Lapunzina, André B.P. van Kuilenburg, Slobodanka Radović, Christel Thauvin-Robinet, Borut Peterlin, Araceli d Tags: Report Source Type: research

Exome-wide Association Study Identifies GREB1L Mutations in Congenital Kidney Malformations
Renal agenesis and hypodysplasia (RHD) are major causes of pediatric chronic kidney disease and are highly genetically heterogeneous. We conducted whole-exome sequencing in 202 case subjects with RHD and identified diagnostic mutations in genes known to be associated with RHD in 7/202 case subjects. In an additional affected individual with RHD and a congenital heart defect, we found a homozygous loss-of-function (LOF) variant in SLIT3, recapitulating phenotypes reported with Slit3 inactivation in the mouse. (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - November 2, 2017 Category: Genetics & Stem Cells Authors: Simone Sanna-Cherchi, Kamal Khan, Rik Westland, Priya Krithivasan, Lorraine Fievet, Hila Milo Rasouly, Iuliana Ionita-Laza, Valentina P. Capone, David A. Fasel, Krzysztof Kiryluk, Sitharthan Kamalakaran, Monica Bodria, Edgar A. Otto, Matthew G. Sampson, C Tags: Article Source Type: research

Mutations in Fibronectin Cause a Subtype of Spondylometaphyseal Dysplasia with “Corner Fractures”
Fibronectin is a master organizer of extracellular matrices (ECMs) and promotes the assembly of collagens, fibrillin-1, and other proteins. It is also known to play roles in skeletal tissues through its secretion by osteoblasts, chondrocytes, and mesenchymal cells. Spondylometaphyseal dysplasias (SMDs) comprise a diverse group of skeletal dysplasias and often manifest as short stature, growth-plate irregularities, and vertebral anomalies, such as scoliosis. By comparing the exomes of individuals with SMD with the radiographic appearance of “corner fractures” at metaphyses, we identified three individuals with f...
Source: The American Journal of Human Genetics - November 2, 2017 Category: Genetics & Stem Cells Authors: Chae Syng Lee, He Fu, Nissan Baratang, Justine Rousseau, Heena Kumra, V. Reid Sutton, Marcello Niceta, Andrea Ciolfi, Guilherme Yamamoto, D ébora Bertola, Carlo L. Marcelis, Dorien Lugtenberg, Andrea Bartuli, Choel Kim, Julie Hoover-Fong, Nara Sobreira, Tags: Report Source Type: research

Mutations in GPAA1, Encoding a GPI Transamidase Complex Protein, Cause Developmental Delay, Epilepsy, Cerebellar Atrophy, and Osteopenia
Approximately one in every 200 mammalian proteins is anchored to the cell membrane through a glycosylphosphatidylinositol (GPI) anchor. These proteins play important roles notably in neurological development and function. To date, more than 20 genes have been implicated in the biogenesis of GPI-anchored proteins. GPAA1 (glycosylphosphatidylinositol anchor attachment 1) is an essential component of the transamidase complex along with PIGK, PIGS, PIGT, and PIGU (phosphatidylinositol-glycan biosynthesis classes K, S, T, and U, respectively). (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - November 2, 2017 Category: Genetics & Stem Cells Authors: Thi Tuyet Mai Nguyen, Yoshiko Murakami, Eamonn Sheridan, Sophie Ehresmann, Justine Rousseau, Anik St-Denis, Guoliang Chai, Norbert F. Ajeawung, Laura Fairbrother, Tyler Reimschisel, Alexandra Bateman, Elizabeth Berry-Kravis, Fan Xia, Jessica Tardif, David Tags: Report Source Type: research