Pérot, Jean-Baptiste Célestine, Marina Palombo, Marco Dhenain, Marc Humbert, Sandrine Brouillet, Emmanuel Flament, Julien
Published in
Human molecular genetics
Pathogenesis of the inherited neurodegenerative disorder Huntington's disease (HD) is progressive with a long presymptomatic phase in which subtle changes occur up to 15 years before the onset of symptoms. Thus, there is a need for early, functional biomarker to better understand disease progression and to evaluate treatment efficacy far from onset...
Geertsma, Haley M Suk, Terry R Ricke, Konrad M Horsthuis, Kyra Parmasad, Jean-Louis A Fisk, Zoe A Callaghan, Steve M Rousseaux, Maxime W C
Published in
Human molecular genetics
A growing body of evidence suggests that nuclear alpha-synuclein (αSyn) plays a role in the pathogenesis of Parkinson's disease (PD). However, this question has been difficult to address as controlling the localization of αSyn in experimental systems often requires protein overexpression, which affects its aggregation propensity. To overcome this, ...
Xu, Keren Li, Shaobo Pandey, Priyatama Kang, Alice Y Morimoto, Libby M Mancuso, Nicholas Ma, Xiaomei Metayer, Catherine Wiemels, Joseph L de Smith, Adam J
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Published in
Human molecular genetics
Genome-wide association studies have identified a growing number of single nucleotide polymorphisms (SNPs) associated with childhood acute lymphoblastic leukemia (ALL), yet the functional roles of most SNPs are unclear. Multiple lines of evidence suggest that epigenetic mechanisms may mediate the impact of heritable genetic variation on phenotypes....
Lee, Richard G Balasubramaniam, Shanti Stentenbach, Maike Kralj, Tom McCubbin, Tim Padman, Benjamin Smith, Janine Riley, Lisa G Priyadarshi, Archana Peng, Liuyu
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Published in
Human molecular genetics
Mitochondrial diseases are a group of inherited diseases with highly varied and complex clinical presentations. Here, we report four individuals, including two siblings, affected by a progressive mitochondrial encephalopathy with biallelic variants in the cardiolipin biosynthesis gene CRLS1. Three affected individuals had a similar infantile presen...
Song, Dan Takahashi, Gou Zheng, Yun-Wen Matsuo-Takasaki, Mami Li, Jingyue Takami, Miho An, Yuri Hemmi, Yasuko Miharada, Natsumi Fujioka, Tsuyoshi
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Published in
Human molecular genetics
Wilson's disease (WD) is a copper metabolic disorder caused by a defective ATP7B function. Conventional therapies cause severe side effects and significant variation in efficacy, according to cohort studies. Thus, exploring new therapeutic approaches to prevent progression to liver failure is urgent. To study the physiology and pathology of WD, imm...
Mertens, Joke Regin, Marius De Munck, Neelke Couvreu de Deckersberg, Edouard Belva, Florence Sermon, Karen Tournaye, Herman Blockeel, Christophe Van de Velde, Hilde Spits, Claudia
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Published in
Human molecular genetics
Humans present remarkable diversity in their mitochondrial DNA (mtDNA) in terms of variants across individuals as well as across tissues and even cells within one person. We have investigated the timing of the first appearance of this variant-driven mosaicism. For this, we deep-sequenced the mtDNA of 254 oocytes from 85 donors, 158 single blastomer...
Jefri, Malvin Zhang, Xin Stumpf, Patrick S Zhang, Li Peng, Huashan Hettige, Nuwan Theroux, Jean-Francois Aouabed, Zahia Wilson, Khadija Deshmukh, Shriya
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Published in
Human molecular genetics
Kabuki syndrome is frequently caused by loss-of-function mutations in one allele of histone 3 lysine 4 (H3K4) methyltransferase KMT2D and is associated with problems in neurological, immunological and skeletal system development. We generated heterozygous KMT2D knockout and Kabuki patient-derived cell models to investigate the role of reduced dosag...
Schaffner, Samantha L Wassouf, Zinah Lazaro, Diana F Xylaki, Mary Gladish, Nicole Lin, David T S MacIsaac, Julia Ramadori, Katia Hentrich, Thomas Schulze-Hentrich, Julia M
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Published in
Human molecular genetics
Parkinson's disease (PD) is a neurological disorder with complex interindividual etiology that is becoming increasingly prevalent worldwide. Elevated alpha-synuclein levels can increase risk of PD and may influence epigenetic regulation of PD pathways. Here, we report genome-wide DNA methylation and hydroxymethylation alterations associated with ov...
Wang, Ke Cadzow, Murray Bixley, Matt Leask, Megan P Merriman, Marilyn E Yang, Qiangzhen Li, Zhiqiang Takei, Riku Phipps-Green, Amanda Major, Tanya J
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Published in
Human molecular genetics
Gout is of particularly high prevalence in the Māori and Pacific (Polynesian) populations of Aotearoa New Zealand (NZ). Here, we investigated the contribution of common population-specific copy number variation (CNV) to gout in the Aotearoa NZ Polynesian population. Microarray-generated genome-wide genotype data from Aotearoa NZ Polynesian individu...
Java, Anuja Pozzi, Nicola Schroeder, Molly C Hu, Zheng Huan, Tianxiao Seddon, Johanna M Atkinson, John
Published in
Human molecular genetics
Factor I (FI) is a serine protease inhibitor of the complement system. Heterozygous rare genetic variants in complement factor I (CFI) are associated with advanced age-related macular degeneration (AMD). The clinical impact of these variants is unknown since a majority have not been functionally characterized and are classified as 'variants of unce...
