Search

Your search keyword '"Weissglas-Volkov, Daphna"' showing total 50 results
Start Over Author "Weissglas-Volkov, Daphna"
50 results on '"Weissglas-Volkov, Daphna"'

1. A Multimodal Dataset of 21,412 Recorded Nights for Sleep and Respiratory Research

Author

Diament, Alon, Gorodetski, Maria, Jankelow, Adam, Keshet, Ayya, Shor, Tal, Weissglas-Volkov, Daphna, Rossman, Hagai, and Segal, Eran

Subjects
Computer Science - Machine Learning, Electrical Engineering and Systems Science - Signal Processing
Abstract

This study introduces a novel, rich dataset obtained from home sleep apnea tests using the FDA-approved WatchPAT-300 device, collected from 7,077 participants over 21,412 nights. The dataset comprises three levels of sleep data: raw multi-channel time-series from sensors, annotated sleep events, and computed summary statistics, which include 447 features related to sleep architecture, sleep apnea, and heart rate variability (HRV). We present reference values for Apnea/Hypopnea Index (AHI), sleep efficiency, Wake After Sleep Onset (WASO), and HRV sample entropy, stratified by age and sex. Moreover, we demonstrate that the dataset improves the predictive capability for various health related traits, including body composition, bone density, blood sugar levels and cardiovascular health. These results illustrate the dataset's potential to advance sleep research, personalized healthcare, and machine learning applications in biomedicine., Comment: Extended Abstract presented at Machine Learning for Health (ML4H) symposium 2023, December 10th, 2023, New Orleans, United States, 14 pages

Published
2023

4. Mutations in TSPEAR, Encoding a Regulator of Notch Signaling, Affect Tooth and Hair Follicle Morphogenesis.

Author

Peled, Alon, Sarig, Ofer, Samuelov, Liat, Bertolini, Marta, Ziv, Limor, Weissglas-Volkov, Daphna, Eskin-Schwartz, Marina, Adase, Christopher A, Malchin, Natalia, Bochner, Ron, Fainberg, Gilad, Goldberg, Ilan, Sugawara, Koji, Baniel, Avital, Tsuruta, Daisuke, Luxenburg, Chen, Adir, Noam, Duverger, Olivier, Morasso, Maria, Shalev, Stavit, Gallo, Richard L, Shomron, Noam, Paus, Ralf, and Sprecher, Eli

Subjects
Hair Follicle, Tooth, Animals, Humans, Mice, Ectodermal Dysplasia, Proteins, Pedigree, DNA Mutational Analysis, Signal Transduction, Cell Differentiation, Gene Expression Regulation, Developmental, Morphogenesis, Frameshift Mutation, Receptor, Notch1, Gene Expression Regulation, Developmental, Receptor, Notch1, Genetics, Developmental Biology
Abstract

Despite recent advances in our understanding of the pathogenesis of ectodermal dysplasias (EDs), the molecular basis of many of these disorders remains unknown. In the present study, we aimed at elucidating the genetic basis of a new form of ED featuring facial dysmorphism, scalp hypotrichosis and hypodontia. Using whole exome sequencing, we identified 2 frameshift and 2 missense mutations in TSPEAR segregating with the disease phenotype in 3 families. TSPEAR encodes the thrombospondin-type laminin G domain and EAR repeats (TSPEAR) protein, whose function is poorly understood. TSPEAR knock-down resulted in altered expression of genes known to be regulated by NOTCH and to be involved in murine hair and tooth development. Pathway analysis confirmed that down-regulation of TSPEAR in keratinocytes is likely to affect Notch signaling. Accordingly, using a luciferase-based reporter assay, we showed that TSPEAR knock-down is associated with decreased Notch signaling. In addition, NOTCH1 protein expression was reduced in patient scalp skin. Moreover, TSPEAR silencing in mouse hair follicle organ cultures was found to induce apoptosis in follicular epithelial cells, resulting in decreased hair bulb diameter. Collectively, these observations indicate that TSPEAR plays a critical, previously unrecognized role in human tooth and hair follicle morphogenesis through regulation of the Notch signaling pathway.

Published
2016

5. Amerindian-specific regions under positive selection harbour new lipid variants in Latinos.

Author

Ko, Arthur, Cantor, Rita M, Weissglas-Volkov, Daphna, Nikkola, Elina, Reddy, Prasad MV Linga, Sinsheimer, Janet S, Pasaniuc, Bogdan, Brown, Robert, Alvarez, Marcus, Rodriguez, Alejandra, Rodriguez-Guillen, Rosario, Bautista, Ivette C, Arellano-Campos, Olimpia, Muñoz-Hernández, Linda L, Salomaa, Veikko, Kaprio, Jaakko, Jula, Antti, Jauhiainen, Matti, Heliövaara, Markku, Raitakari, Olli, Lehtimäki, Terho, Eriksson, Johan G, Perola, Markus, Lohmueller, Kirk E, Matikainen, Niina, Taskinen, Marja-Riitta, Rodriguez-Torres, Maribel, Riba, Laura, Tusie-Luna, Teresa, Aguilar-Salinas, Carlos A, and Pajukanta, Päivi

Subjects
Chromosomes, Human, Pair 8, Chromosomes, Human, Pair 11, Humans, Hypercholesterolemia, Hypertriglyceridemia, Obesity, Genetic Predisposition to Disease, Lipoprotein Lipase, Protein Kinases, Apolipoproteins A, Logistic Models, Case-Control Studies, Genotype, Haplotypes, Polymorphism, Single Nucleotide, Adult, Middle Aged, Indians, North American, European Continental Ancestry Group, Mexico, Female, Male, Dyslipidemias, Genome-Wide Association Study, Young Adult, Nuclear Receptor Subfamily 1, Group F, Member 1, Apolipoprotein A-V
Abstract

Dyslipidemia and obesity are especially prevalent in populations with Amerindian backgrounds, such as Mexican-Americans, which predispose these populations to cardiovascular disease. Here we design an approach, known as the cross-population allele screen (CPAS), which we conduct prior to a genome-wide association study (GWAS) in 19,273 Europeans and Mexicans, in order to identify Amerindian risk genes in Mexicans. Utilizing CPAS to restrict the GWAS input variants to only those differing in frequency between the two populations, we identify novel Amerindian lipid genes, receptor-related orphan receptor alpha (RORA) and salt-inducible kinase 3 (SIK3), and three loci previously unassociated with dyslipidemia or obesity. We also detect lipoprotein lipase (LPL) and apolipoprotein A5 (APOA5) harbouring specific Amerindian signatures of risk variants and haplotypes. Notably, we observe that SIK3 and one novel lipid locus underwent positive selection in Mexicans. Furthermore, after a high-fat meal, the SIK3 risk variant carriers display high triglyceride levels. These findings suggest that Amerindian-specific genetic architecture leads to a higher incidence of dyslipidemia and obesity in modern Mexicans.

Published
2014

6. Adipose Co-expression networks across Finns and Mexicans identify novel triglyceride-associated genes

Author

Haas, Blake E, Horvath, Steve, Pietiläinen, Kirsi H, Cantor, Rita M, Nikkola, Elina, Weissglas-Volkov, Daphna, Rissanen, Aila, Civelek, Mete, Cruz-Bautista, Ivette, Riba, Laura, Kuusisto, Johanna, Kaprio, Jaakko, Tusie-Luna, Teresa, Laakso, Markku, Aguilar-Salinas, Carlos A, and Pajukanta, Päivi

Abstract

Abstract Background High serum triglyceride (TG) levels is an established risk factor for coronary heart disease (CHD). Fat is stored in the form of TGs in human adipose tissue. We hypothesized that gene co-expression networks in human adipose tissue may be correlated with serum TG levels and help reveal novel genes involved in TG regulation. Methods Gene co-expression networks were constructed from two Finnish and one Mexican study sample using the blockwiseModules R function in Weighted Gene Co-expression Network Analysis (WGCNA). Overlap between TG-associated networks from each of the three study samples were calculated using a Fisher’s Exact test. Gene ontology was used to determine known pathways enriched in each TG-associated network. Results We measured gene expression in adipose samples from two Finnish and one Mexican study sample. In each study sample, we observed a gene co-expression network that was significantly associated with serum TG levels. The TG modules observed in Finns and Mexicans significantly overlapped and shared 34 genes. Seven of the 34 genes (ARHGAP30, CCR1, CXCL16, FERMT3, HCST, RNASET2, SELPG) were identified as the key hub genes of all three TG modules. Furthermore, two of the 34 genes (ARHGAP9, LST1) reside in previous TG GWAS regions, suggesting them as the regional candidates underlying the GWAS signals. Conclusions This study presents a novel adipose gene co-expression network with 34 genes significantly correlated with serum TG across populations.

Published
2012

8. GWAS and PRS-PheWAS Across Complex Phenotypes in the Human Phenotype Project

Author

Levine, Zachary, primary, Kalka, Iris, additional, Kolobkov, Dmitry, additional, Rossman, Hagai, additional, Godneva, Anastasia, additional, Shilo, Smadar, additional, Keshet, Ayya, additional, Weissglas-Volkov, Daphna, additional, Shor, Tal, additional, Diament, Alon, additional, Barkan, Yeela Talmor, additional, Aviv, Yaron, additional, Sharon, Tom, additional, Weinberger, Adina, additional, Segal, Eran, additional, and Administrator, Sneak Peek, additional

Published
2023
Full Text
View/download PDF

13. WW-Domain-Containing Oxidoreductase Is Associated with Low Plasma HDL-C Levels

Author

Lee, Jenny C., Weissglas-Volkov, Daphna, Kyttälä, Mira, Dastani, Zari, Cantor, Rita M., Sobel, Eric M., Plaisier, Christopher L., Engert, James C., van Greevenbroek, Marleen M.J., Kane, John P., Malloy, Mary J., Pullinger, Clive R., Huertas-Vazquez, Adriana, Aguilar-Salinas, Carlos A., Tusie-Luna, Teresa, de Bruin, Tjerk W.A., Aouizerat, Bradley E., van der Kallen, Carla C.J., Croce, Carlo M., Aqeilan, Rami I., Marcil, Michel, Viikari, Jorma S.A., Lehtimäki, Terho, Raitakari, Olli T., Kuusisto, Johanna, Laakso, Markku, Taskinen, Marja-Riitta, Genest, Jacques, and Pajukanta, Päivi

Published
2008
Full Text
View/download PDF

14. The N342S MYLIP polymorphism is associated with high total cholesterol and increased LDL receptor degradation in humans

Author

Weissglas-Volkov, Daphna, Calkin, Anna C., Tusie-Luna, Teresa, Sinsheimer, Janet S., Zelcer, Noam, Riba, Laura, Tino, Ana Maria Vargas, Ordonez-Sanchez, Maria Luisa, Cruz-Bautista, Ivette, Aguilar-Salinas, Carlos A., Tontonoz, Peter, and Pajukanta, Paivi

Subjects
Complications and side effects, Physiological aspects, Research, Genetic aspects, Risk factors, Low density lipoproteins -- Research -- Physiological aspects -- Genetic aspects, Single nucleotide polymorphisms -- Research -- Physiological aspects -- Genetic aspects, Hypercholesterolemia -- Genetic aspects -- Risk factors -- Complications and side effects -- Research, Cardiovascular diseases -- Research -- Risk factors -- Genetic aspects -- Complications and side effects
Abstract

Introduction Atherosclerotic cardiovascular disease (ASCVD) affects more than 1 in 3 American adults, and the burden arising from this in terms of mortality and financial cost is great (1). Modifiable [...], Atherosclerotic cardiovascular disease (ASCVD) affects more than 1 in 3 American adults. Hypercholesterolemia is a major treatable risk factor for ASCVD, yet many individuals fail to reach target levels of LDL-cholesterol (LDL-C) through the use of statins and lifestyle changes. The E3 ubiquitin ligase myosin regulatory light chain-interacting protein (MYLIP; also known as IDOL) is a recently identified regulator of the LDL receptor (LDLR) pathway. Genome-wide association studies (GWASs) in populations of mixed European descent have identified noncoding variants in the MYLIP region as being associated with LDL-C levels, but no underlying functional variants were pinpointed. In order to fine-map actual susceptibility variants, we studied a population demographically distinct from the discovery population to ensure a different pattern of linkage disequilibrium. Our analysis revealed that in a Mexican population, the nonsynonymous SNP rs9370867, which encodes the N342S amino acid substitution, is an underlying functional variant that was associated with high total cholesterol and accounted for one of the previous significant GWAS signals. Functional characterization showed that the Asn-encoding allele was associated with more potent LDLR degradation and decreased LDL uptake. Mutagenesis of residue 342 failed to affect intrinsic MYLIP E3 ligase activity, but it was critical for LDLR targeting. Our findings suggest that modulation of MYLIP activity can affect LDL-C levels and that pharmacologic inhibition of MYLIP activity might be a useful strategy in the treatment of dyslipidemia and ASCVD.

Published
2011
Full Text
View/download PDF

15. Genomic study in Mexicans identifies a new locus for triglycerides and refines European lipid loci

Author

Weissglas-Volkov, Daphna, Aguilar-Salinas, Carlos A, Nikkola, Elina, Deere, Kerry A, Cruz-Bautista, Ivette, Arellano-Campos, Olimpia, Muñoz-Hernandez, Linda Liliana, Gomez-Munguia, Lizeth, Ordoñez-Sánchez, Maria Luisa, Reddy, Prasad M V Linga, Lusis, Aldons J, Matikainen, Niina, Taskinen, Marja-Riitta, Riba, Laura, Cantor, Rita M, Sinsheimer, Janet S, Tusie-Luna, Teresa, and Pajukanta, Päivi

Published
2013
Full Text
View/download PDF

16. Relative matching using low coverage sequencing

Author

Petter, Ella, primary, Schweiger, Regev, additional, Shahino, Bar, additional, Shor, Tal, additional, Aker, Malka, additional, Almog, Lior, additional, Weissglas-Volkov, Daphna, additional, Naveh, Yoav, additional, Navon, Oron, additional, Carmi, Shai, additional, Li, Jeremiah H., additional, Berisa, Tomaz, additional, Pickrell, Joseph K., additional, and Erlich, Yaniv, additional

Published
2020
Full Text
View/download PDF

17. Phenotypic suppression of acral peeling skin syndrome in a patient with autosomal recessive congenital ichthyosis

Author

Mohamad, Janan, primary, Nanda, Arti, additional, Pavlovsky, Mor, additional, Peled, Alon, additional, Malchin, Natalia, additional, Malovitski, Kiril, additional, Pramanik, Rashida, additional, Weissglas‐Volkov, Daphna, additional, Shomron, Noam, additional, McGrath, John, additional, Sprecher, Eli, additional, and Sarig, Ofer, additional

Published
2020
Full Text
View/download PDF

19. Loss of protocadherin-12 leads to Diencephalic-Mesencephalic Junction Dysplasia syndrome

Author

McEvoy-Venneri, Jennifer, Einhorn, Yaron, Guemez-Gamboa, Alicia, Heimer, Gali, Bilguvar, Kaya, Musaev, Damir, Shomron, Noam, Porat, Yuval, Akizu, Naiara, Gabriel, Stacey, Pillar, Nir, Issa, Mahmoud Y., Erson-Omay, Emine Z., Gregor, Anne, PER, HÜSEYİN, Ben-Zeev, Bruria, Gunel, Murat, Yasuno, Katsuhito, Fang, Rebecca, Copeland, Brett, Saleem, Sahar N., Rosti, Rasim Ozgur, Silhavy, Jennifer L., Belandres, Denice, Lewis, Steven M., Weissglas-Volkov, Daphna, Caglayan, Ahmet Okay, Akgumus, Gozde Tugce, Gumus, Hakan, Gleeson, Joseph G., Kumandas, Sefer, Stanley, Valentina, Bayram, Ayse Kacar, Schroth, Jana, and Zaki, Maha S.

Subjects
Male, Child, Preschool, Mutation, Infant, Newborn, Humans, Infant, Female, Cadherins, Child, Nervous System Malformations, Article, Protocadherins, Brain Stem
Abstract

Objective Methods To identify causes of the autosomal-recessive malformation, diencephalic-mesencephalic junction dysplasia (DMJD) syndrome. Eight families with DMJD were studied by whole-exome or targeted sequencing, with detailed clinical and radiological characterization. Patient-derived induced pluripotent stem cells were derived into neural precursor and endothelial cells to study gene expression. Results Interpretation All patients showed biallelic mutations in the nonclustered protocadherin-12 (PCDH12) gene. The characteristic clinical presentation included progressive microcephaly, craniofacial dysmorphism, psychomotor disability, epilepsy, and axial hypotonia with variable appendicular spasticity. Brain imaging showed brainstem malformations and with frequent thinned corpus callosum with punctate brain calcifications, reflecting expression of PCDH12 in neural and endothelial cells. These cells showed lack of PCDH12 expression and impaired neurite outgrowth. DMJD patients have biallelic mutations in PCDH12 and lack of protein expression. These patients present with characteristic microcephaly and abnormalities of white matter tracts. Such pathogenic variants predict a poor outcome as a result of brainstem malformation and evidence of white matter tract defects, and should be added to the phenotypic spectrum associated with PCDH12-related conditions. Ann Neurol 2018;84:646-655

Published
2018

20. Loss of Protocadherin‐12 L eads to D iencephalic‐ M esencephalic J unction D ysplasia S yndrome

Author

Guemez‐Gamboa, Alicia, primary, Çağlayan, Ahmet Okay, additional, Stanley, Valentina, additional, Gregor, Anne, additional, Zaki, Maha S., additional, Saleem, Sahar N., additional, Musaev, Damir, additional, McEvoy‐Venneri, Jennifer, additional, Belandres, Denice, additional, Akizu, Naiara, additional, Silhavy, Jennifer L., additional, Schroth, Jana, additional, Rosti, Rasim Ozgur, additional, Copeland, Brett, additional, Lewis, Steven M., additional, Fang, Rebecca, additional, Issa, Mahmoud Y., additional, Per, Huseyin, additional, Gumus, Hakan, additional, Bayram, Ayse Kacar, additional, Kumandas, Sefer, additional, Akgumus, Gozde Tugce, additional, Erson‐Omay, Emine Z., additional, Yasuno, Katsuhito, additional, Bilguvar, Kaya, additional, Heimer, Gali, additional, Pillar, Nir, additional, Shomron, Noam, additional, Weissglas‐Volkov, Daphna, additional, Porat, Yuval, additional, Einhorn, Yaron, additional, Gabriel, Stacey, additional, Ben‐Zeev, Bruria, additional, Gunel, Murat, additional, and Gleeson, Joseph G., additional

Published
2018
Full Text
View/download PDF

22. Corrigendum to “X-linked elliptocytosis with impaired growth is related to mutated AMMECR1” [Gene 606C (2017) 47–52]

Author

Basel-Vanagaite, Lina, primary, Pillar, Nir, additional, Isakov, Ofer, additional, Smirin-Yosef, Pola, additional, Lagovsky, Irina, additional, Orenstein, Naama, additional, Salmon-Divon, Mali, additional, Tamary, Hannah, additional, Zaft, Tami, additional, Bazak, Lily, additional, Meyerovitch, Joseph, additional, Pelli, Tal, additional, Botchan, Shay, additional, Farberov, Luba, additional, Weissglas-Volkov, Daphna, additional, and Shomron, Noam, additional

Published
2018
Full Text
View/download PDF

23. X-linked elliptocytosis with impaired growth is related to mutated AMMECR1

Author

Basel-Vanagaite, Lina, primary, Pillar, Nir, additional, Isakov, Ofer, additional, Smirin-Yosef, Pola, additional, Lagovsky, Irina, additional, Orenstein, Naama, additional, Salmon-Divon, Mali, additional, Tamary, Hannah, additional, Zaft, Tami, additional, Bazak, Lily, additional, Meyerovitch, Joseph, additional, Pelli, Tal, additional, Botchan, Shay, additional, Farberov, Luba, additional, Weissglas-Volkov, Daphna, additional, and Shomron, Noam, additional

Published
2017
Full Text
View/download PDF

24. Local microRNA delivery targets Palladin and prevents metastatic breast cancer

Author

Massachusetts Institute of Technology. Institute for Medical Engineering & Science, Osorio De Castro Conde, Joao, Oliva Jorge, Nuria, Artzi, Natalie, Gilam, Avital, Weissglas-Volkov, Daphna, Friedman, Eitan, Shomron, Noam, Oliva, Nuria, Massachusetts Institute of Technology. Institute for Medical Engineering & Science, Osorio De Castro Conde, Joao, Oliva Jorge, Nuria, Artzi, Natalie, Gilam, Avital, Weissglas-Volkov, Daphna, Friedman, Eitan, Shomron, Noam, and Oliva, Nuria

Abstract

Metastasis is the primary cause for mortality in breast cancer. MicroRNAs, gene expression master regulators, constitute an attractive candidate to control metastasis. Here we show that breast cancer metastasis can be prevented by miR-96 or miR-182 treatment, and decipher the mechanism of action. We found that miR-96/miR-182 downregulate Palladin protein levels, thereby reducing breast cancer cell migration and invasion. A common SNP, rs1071738, at the miR-96/miR-182-binding site within the Palladin 3′-UTR abolishes miRNA:mRNA binding, thus diminishing Palladin regulation by these miRNAs. Regulation is successfully restored by applying complimentary miRNAs. A hydrogel-embedded, gold-nanoparticle-based delivery vehicle provides efficient local, selective, and sustained release of miR-96/miR-182, markedly suppressing metastasis in a breast cancer mouse model. Combined delivery of the miRNAs with a chemotherapy drug, cisplatin, enables significant primary tumour shrinkage and metastasis prevention. Our data corroborate the role of miRNAs in metastasis, and suggest miR-96/miR-182 delivery as a potential anti-metastatic drug., Israel Cancer Research Fund, Israel Cancer Association, Israel Science Foundation (1852/16), Marie Curie International Outgoing Fellowship (FP7-PEOPLE-2013-IOF, Project 626386)

Published
2017

25. The WWOX Gene Modulates HDL and Lipid Metabolism

Author

Iatan, Iulia, Choi, Hong Y., Ruel, Isabelle, Linga Reddy, M.V. Prasad, Kil, Hyunsuk, Lee, Jaeho, Abu Odeh, Mohammad, Salah, Zaidoun, Abu-Remaileh, Muhannad, Weissglas-Volkov, Daphna, Nikkola, Elina, Civelek, Mete, Awan, Zuhier, Croce, Carlo M., Aqeilan, Rami I., Pajukanta, Päivi, Aldaz, C. Marcelo, and Genest, Jacques

Subjects
Adult, Male, Adolescent, Polymorphism, Single Nucleotide, Article, Mice, Angiopoietin-Like Protein 4, Animals, Humans, fas Receptor, Alleles, Triglycerides, Aged, Mice, Knockout, Apolipoprotein A-I, Tumor Suppressor Proteins, Cholesterol, HDL, High-Throughput Nucleotide Sequencing, Lipase, Sequence Analysis, DNA, Middle Aged, Lipid Metabolism, Up-Regulation, Mice, Inbred C57BL, Haplotypes, Liver, WW Domain-Containing Oxidoreductase, Female, Lipoproteins, HDL, Oxidoreductases, Angiopoietins, Chromosomes, Human, Pair 16, ATP Binding Cassette Transporter 1
Abstract

Low levels of high-density lipoprotein (HDL) cholesterol constitutes a major risk factor for atherosclerosis. Recent studies from our group reported a genetic association between the WW domain-containing oxidoreductase (WWOX) gene and HDL cholesterol levels. Here, through next-generation resequencing, in vivo functional studies and gene microarray analyses, we investigated the role of WWOX in HDL and lipid metabolism.Using next-generation resequencing of the WWOX region, we first identified 8 variants significantly associated and perfectly segregating with the low-HDL trait in 2 multigenerational French Canadian dyslipidemic families. To understand in vivo functions of WWOX, we used liver-specific Wwox(hep-/-) and total Wwox(-/-) mice models, where we found decreased ApoA-I and Abca1 levels in hepatic tissues. Analyses of lipoprotein profiles in Wwox(-/-), but not Wwox(hep-/-) littermates, also showed marked reductions in serum HDL cholesterol concentrations, concordant with the low-HDL findings observed in families. We next obtained evidence of a sex-specific effect in female Wwox(hep-/-) mice, where microarray analyses revealed an increase in plasma triglycerides and altered lipid metabolic pathways. We further identified a significant reduction in ApoA-I and Lpl and an upregulation in Fas, Angptl4, and Lipg, suggesting that the effects of Wwox involve multiple pathways, including cholesterol homeostasis, ApoA-I/ABCA1 pathway, and fatty acid biosynthesis/triglyceride metabolism.Our data indicate that WWOX disruption alters HDL and lipoprotein metabolism through several mechanisms and may account for the low-HDL phenotype observed in families expressing the WWOX variants. These findings thus describe a novel gene involved in cellular lipid homeostasis, which effects may impact atherosclerotic disease development.

Published
2014

30. Exome Sequencing Identifies Two Rare Variants for Low HDL-C in an Extended Family

Author

Reddy, MV Prasad Linga, Iatan, Iulia, Weissglas-Volkov, Daphna, Nikkola, Elina, Haas, Blake E., Juvonen, Miina, Ruel, Isabelle, Sinsheimer, Janet S., Genest, Jacques, and Pajukanta, Päivi

Subjects
Genotype, Genetic Linkage, Genome, Human, Mutation, Missense, Cholesterol, LDL, Sequence Analysis, DNA, Article, Lipoprotein Lipase, Sex Factors, Humans, ATP-Binding Cassette Transporters, Exome, Family, Alleles, Cells, Cultured, ATP Binding Cassette Transporter 1
Abstract

Exome sequencing is a recently implemented method to discover rare mutations for Mendelian disorders. Less is known about its feasibility to identify genes for complex traits. We used exome sequencing to search for rare variants responsible for a complex trait, low levels of serum high-density lipoprotein cholesterol (HDL-C).We conducted exome sequencing in a large French-Canadian family with 75 subjects available for study, of which 27 had HDL-C values less than the fifth age-sex-specific population percentile. We captured ≈50 Mb of exonic and transcribed sequences of 3 closely related family members with HDL-C levels less than the fifth age-sex percentile and sequenced the captured DNA. Approximately 82,000 variants were detected in each individual, of which 41 rare nonsynonymous variants were shared by the sequenced affected individuals after filtering steps. Two rare nonsynonymous variants in the ATP-binding cassette, subfamily A (ABC1), member 1 (ABCA1), and lipoprotein lipase genes predicted to be damaging were investigated for cosegregation with the low HDL-C trait in the entire extended family. The carriers of either variant had low HDL-C levels, and the individuals carrying both variants had the lowest HDL-C values. Interestingly, the ABCA1 variant exhibited a sex effect which was first functionally identified, and, subsequently, statistically demonstrated using additional French-Canadian families with ABCA1 mutations.This complex combination of 2 rare variants causing low HDL-C in the extended family would not have been identified using traditional linkage analysis, emphasizing the need for exome sequencing of complex lipid traits in unexplained familial cases.

Published
2012

31. Whole-Genome Sequencing Analysis from the Chikungunya Virus Caribbean Outbreak Reveals Novel Evolutionary Genomic Elements

Author

Stapleford, Kenneth A., primary, Moratorio, Gonzalo, additional, Henningsson, Rasmus, additional, Chen, Rubing, additional, Matheus, Séverine, additional, Enfissi, Antoine, additional, Weissglas-Volkov, Daphna, additional, Isakov, Ofer, additional, Blanc, Hervé, additional, Mounce, Bryan C., additional, Dupont-Rouzeyrol, Myrielle, additional, Shomron, Noam, additional, Weaver, Scott, additional, Fontes, Magnus, additional, Rousset, Dominique, additional, and Vignuzzi, Marco, additional

Published
2016
Full Text
View/download PDF

33. Investigation of variants identified in Caucasian genome-wide association studies for plasma HDL cholesterol and triglycerides levels in Mexican dyslipidemic study samples

Author

Weissglas-Volkov, Daphna, Aguilar-Salinas, Carlos A., Sinsheimer, Janet S., Riba, Laura, Huertas-Vazquez, Adriana, Ordoñez-Sánchez, Maria L., Rodriguez-Guillen, Rosario, Cantor, Rita M., Tusie-Luna, Teresa, and Pajukanta, Päivi

Subjects
Hypertriglyceridemia, Genotype, Cholesterol, HDL, Genetic Variation, Polymorphism, Single Nucleotide, Article, White People, Genetics, Population, Gene Frequency, Case-Control Studies, Mexican Americans, Odds Ratio, Humans, Family, Mexico, Alleles, Triglycerides, Dyslipidemias, Genome-Wide Association Study
Abstract

Although epidemiological studies have demonstrated an increased predisposition to low high-density lipoprotein cholesterol and high triglyceride levels in the Mexican population, Mexicans have not been included in any of the previously reported genome-wide association studies for lipids.We investigated 6 single-nucleotide polymorphisms associated with triglycerides, 7 with high-density lipoprotein cholesterol, and 1 with both triglycerides and high-density lipoprotein cholesterol in recent Caucasian genome-wide association studies in Mexican familial combined hyperlipidemia families and hypertriglyceridemia case-control study samples. These variants were within or near the genes ABCA1, ANGPTL3, APOA5, APOB, CETP, GALNT2, GCKR, LCAT, LIPC, LPL (2), MMAB-MVK, TRIB1, and XKR6-AMAC1L2. We performed a combined analysis of the family-based and case-control studies (n=2298) using the Z method to combine statistics. Ten of the single-nucleotide polymorphisms were nominally significant and 5 were significant after Bonferroni correction (P=2.20 x 10(-3) to 2.6 x 10(-11)) for the number of tests performed (APOA5, CETP, GCKR, and GALNT2). Interestingly, our strongest signal was obtained for triglycerides with the minor allele of rs964184 (P=2.6 x 10(-11)) in the APOA1/C3/A4/A5 gene cluster region that is significantly more common in Mexicans (27%) than in whites (12%).It is important to confirm whether known loci have a consistent effect across ethnic groups. We show replication of 5 Caucasian genome-wide association studies lipid associations in Mexicans. The remaining loci will require a comprehensive investigation to exclude or verify their significance in Mexicans. We also demonstrate that rs964184 has a large effect (odds ratio, 1.74) and is more frequent in the Mexican population, and thus it may contribute to the high predisposition to dyslipidemias in Mexicans.

Published
2009

34. Genetic Variation at the Proprotein Convertase Subtilisin/Kexin Type 5 Gene Modulates HDL Cholesterol Levels

Author

Iatan, Iulia, Dastani, Zari, Do, Ron, Weissglas-Volkov, Daphna, Ruel, Isabelle, Lee, Jenny C., Huertas-Vazquez, Adriana, Taskinen, Marja-Riitta, Prat, Annik, Seidah, Nabil G., Pajukanta, Päivi, Engert, James C., and Genest, Jacques

Subjects
Adult, Male, Genotype, Cholesterol, HDL, Genetic Variation, Middle Aged, Polymorphism, Single Nucleotide, Article, White People, Pedigree, Case-Control Studies, Proprotein Convertase 5, Humans, Female, Aged
Abstract

A low level of plasma high-density lipoprotein cholesterol (HDL-C) is a risk factor for cardiovascular disease. HDL particles are modulated by a variety of lipases, including endothelial lipase, a phospholipase present on vascular endothelial cells. The proprotein convertase subtilisin/kexin type 5 (PCSK5) gene product is known to directly inactivate endothelial lipase and indirectly cleave and activate angiopoetin-like protein 3, a natural inhibitor of endothelial lipase. We therefore investigated the effect of human PCSK5 genetic variants on plasma HDL-C levels.Haplotypes at the PCSK5 locus were examined in 9 multigenerational families that included 60 individuals with HDL-C10th percentile. Segregation with low HDL-C in 1 family was found. Sequencing of the PCSK5 gene in 12 probands with HDL-C5th percentile identified 7 novel variants. Using a 2-stage design, we first genotyped these single-nucleotide polymorphisms (SNPs) along with 163 tagSNPs and 12 additional SNPs (n=182 total) in 457 individuals with documented coronary artery disease. We identified 9 SNPs associated with HDL-C (P0.05), with the strongest results for rs11144782 and rs11144766 (P=0.002 and P=0.005, respectively). The SNP rs11144782 was also associated with very low-density lipoprotein (P=0.039), triglycerides (P=0.049), and total apolipoprotein levels (P=0.022). In stage 2, we replicated the association of rs11144766 with HDL-C (P=0.014) in an independent sample of Finnish low HDL-C families. In a combined analysis of both stages (n=883), region-wide significance of rs11144766 and low HDL-C was observed (unadjusted P=1.86x10(-4) and Bonferroni-adjusted P=0.031).We conclude that variability at the PCSK5 locus influences HDL-C levels, possibly through the inactivation of endothelial lipase activity, and, consequently, atherosclerotic cardiovascular disease risk.

Published
2009

35. The WWOX Gene Modulates High-Density Lipoprotein and Lipid Metabolism

Author

Iatan, Iulia, primary, Choi, Hong Y., additional, Ruel, Isabelle, additional, Reddy, M.V. Prasad Linga, additional, Kil, Hyunsuk, additional, Lee, Jaeho, additional, Odeh, Mohammad Abu, additional, Salah, Zaidoun, additional, Abu-Remaileh, Muhannad, additional, Weissglas-Volkov, Daphna, additional, Nikkola, Elina, additional, Civelek, Mete, additional, Awan, Zuhier, additional, Croce, Carlo M., additional, Aqeilan, Rami I., additional, Pajukanta, Päivi, additional, Aldaz, C. Marcelo, additional, and Genest, Jacques, additional

Published
2014
Full Text
View/download PDF

36. Abstract 68: The WWOX Gene Modulates HDL Metabolism and Lipoprotein Gene Expression

Author

Iatan, Iulia, primary, Y. Choi, Hong, additional, Ruel, Isabelle, additional, Reddy, MV Prasad Linga, additional, Kil, Hyunsuk, additional, Lee, Jaeho, additional, Odeh, Mohammad Abu, additional, Salah, Zaidoun, additional, Abu-Remaileh, Muhannad, additional, Weissglas-Volkov, Daphna, additional, Nikkola, Elina, additional, Civelek, Mete, additional, Awan, Zuhier, additional, Croce, Carlo M, additional, Aqeilan, Rami I, additional, Pajukanta, Päivi, additional, Aldaz, Marcelo C, additional, and Genest, Jacques, additional

Published
2013
Full Text
View/download PDF

38. Transgenic Expression and Genetic Variation of Lmf1 Affect LPL Activity in Mice and Humans

Author

Hosseini, Maryam, primary, Ehrhardt, Nicole, additional, Weissglas-Volkov, Daphna, additional, Lai, Ching-Mei, additional, Mao, Hui Z., additional, Liao, Jo-Ling, additional, Nikkola, Elina, additional, Bensadoun, André, additional, Taskinen, Marja-Riitta, additional, Doolittle, Mark H., additional, Pajukanta, Päivi, additional, and Péterfy, Miklós, additional

Published
2012
Full Text
View/download PDF

39. Evidence of How rs7575840 Influences Apolipoprotein B–Containing Lipid Particles

Author

Haas, Blake E., primary, Weissglas-Volkov, Daphna, additional, Aguilar-Salinas, Carlos A., additional, Nikkola, Elina, additional, Vergnes, Laurent, additional, Cruz-Bautista, Ivette, additional, Riba, Laura, additional, Stancakova, Alena, additional, Kuusisto, Johanna, additional, Soininen, Pasi, additional, Kangas, Antti J., additional, Ala-Korpela, Mika, additional, Tusie-Luna, Teresa, additional, Laakso, Markku, additional, and Pajukanta, Päivi, additional

Published
2011
Full Text
View/download PDF

40. Investigation of Variants Identified in Caucasian Genome-Wide Association Studies for Plasma High-Density Lipoprotein Cholesterol and Triglycerides Levels in Mexican Dyslipidemic Study Samples

Author

Weissglas-Volkov, Daphna, primary, Aguilar-Salinas, Carlos A., additional, Sinsheimer, Janet S., additional, Riba, Laura, additional, Huertas-Vazquez, Adriana, additional, Ordoñez-Sánchez, Maria L., additional, Rodriguez-Guillen, Rosario, additional, Cantor, Rita M., additional, Tusie-Luna, Teresa, additional, and Pajukanta, Päivi, additional

Published
2010
Full Text
View/download PDF

41. Identification of Two Common Variants Contributing to Serum Apolipoprotein B Levels in Mexicans

Author

Weissglas-Volkov, Daphna, primary, Plaisier, Christopher L., additional, Huertas-Vazquez, Adriana, additional, Cruz-Bautista, Ivette, additional, Riaño-Barros, Daniela, additional, Herrera-Hernandez, Miguel, additional, Riba, Laura, additional, Cantor, Rita M., additional, Sinsheimer, Janet S., additional, Aguilar-Salinas, Carlos A., additional, Tusie-Luna, Teresa, additional, and Pajukanta, Päivi, additional

Published
2010
Full Text
View/download PDF

42. Genetic Variation at the Proprotein Convertase Subtilisin/Kexin Type 5 Gene Modulates High-Density Lipoprotein Cholesterol Levels

Author

Iatan, Iulia, primary, Dastani, Zari, additional, Do, Ron, additional, Weissglas-Volkov, Daphna, additional, Ruel, Isabelle, additional, Lee, Jenny C., additional, Huertas-Vazquez, Adriana, additional, Taskinen, Marja-Riitta, additional, Prat, Annik, additional, Seidah, Nabil G., additional, Pajukanta, Päivi, additional, Engert, James C., additional, and Genest, Jacques, additional

Published
2009
Full Text
View/download PDF

43. The ATF6-Met[67]Val Substitution Is Associated With Increased Plasma Cholesterol Levels

Author

Meex, Steven J.R., primary, Weissglas-Volkov, Daphna, additional, van der Kallen, Carla J.H., additional, Thuerauf, Donna J., additional, van Greevenbroek, Marleen M.J., additional, Schalkwijk, Casper G., additional, Stehouwer, Coen D.A., additional, Feskens, Edith J.M., additional, Heldens, Lonneke, additional, Ayoubi, Torik A., additional, Hofker, Marten H., additional, Wouters, Bradly G., additional, Vlietinck, Robert, additional, Sinsheimer, Janet S., additional, Taskinen, Marja-Riitta, additional, Kuusisto, Johanna, additional, Laakso, Markku, additional, de Bruin, Tjerk W.A., additional, Pajukanta, Päivi, additional, and Glembotski, Christopher C., additional

Published
2009
Full Text
View/download PDF

44. Galanin Preproprotein Is Associated With Elevated Plasma Triglycerides

Author

Plaisier, Christopher L., primary, Kyttälä, Mira, additional, Weissglas-Volkov, Daphna, additional, Sinsheimer, Janet S., additional, Huertas-Vazquez, Adriana, additional, Riba, Laura, additional, Ramírez-Jiménez, Salvador, additional, de Bruin, Tjerk W.A., additional, Tusié-Luna, Teresa, additional, Aouizerat, Bradley E., additional, Pullinger, Clive R., additional, Malloy, Mary J., additional, Kane, John P., additional, Cruz-Bautista, Ivette, additional, Herrera, Miguel F., additional, Aguilar-Salinas, Carlos, additional, Kuusisto, Johanna, additional, Laakso, Markku, additional, Taskinen, Marja-Riitta, additional, van der Kallen, Carla J.H., additional, and Pajukanta, Päivi, additional

Published
2009
Full Text
View/download PDF

46. Mutations in LMF1 cause combined lipase deficiency and severe hypertriglyceridemia

Author

Péterfy, Miklós, primary, Ben-Zeev, Osnat, additional, Mao, Hui Z, additional, Weissglas-Volkov, Daphna, additional, Aouizerat, Bradley E, additional, Pullinger, Clive R, additional, Frost, Philip H, additional, Kane, John P, additional, Malloy, Mary J, additional, Reue, Karen, additional, Pajukanta, Päivi, additional, and Doolittle, Mark H, additional

Published
2007
Full Text
View/download PDF

47. USF1 Contributes to High Serum Lipid Levels in Dutch FCHL Families and U.S. Whites With Coronary Artery Disease

Author

Lee, Jenny C., primary, Weissglas-Volkov, Daphna, additional, Kyttälä, Mira, additional, Sinsheimer, Janet S., additional, Jokiaho, Anne, additional, de Bruin, Tjerk W.A., additional, Lusis, Aldons J., additional, Brennan, Marie-Luise, additional, van Greevenbroek, Marleen M.J., additional, van der Kallen, Carla J.H., additional, Hazen, Stanley L., additional, and Pajukanta, Päivi, additional

Published
2007
Full Text
View/download PDF

48. The WWOXGene Modulates High-Density Lipoprotein and Lipid Metabolism

Author

Iatan, Iulia, Choi, Hong Y., Ruel, Isabelle, Reddy, M.V. Prasad Linga, Kil, Hyunsuk, Lee, Jaeho, Odeh, Mohammad Abu, Salah, Zaidoun, Abu-Remaileh, Muhannad, Weissglas-Volkov, Daphna, Nikkola, Elina, Civelek, Mete, Awan, Zuhier, Croce, Carlo M., Aqeilan, Rami I., Pajukanta, Päivi, Aldaz, C. Marcelo, and Genest, Jacques

Abstract

Low levels of high-density lipoprotein (HDL) cholesterol constitutes a major risk factor for atherosclerosis. Recent studies from our group reported a genetic association between the WW domain-containing oxidoreductase (WWOX) gene and HDL cholesterol levels. Here, through next-generation resequencing, in vivo functional studies and gene microarray analyses, we investigated the role of WWOXin HDL and lipid metabolism.

Published
2014
Full Text
View/download PDF

49. Genetic Variation at the Proprotein Convertase Subtilisin/Kexin Type 5Gene Modulates High-Density Lipoprotein Cholesterol Levels

Author

Iatan, Iulia, Dastani, Zari, Do, Ron, Weissglas-Volkov, Daphna, Ruel, Isabelle, Lee, Jenny C., Huertas-Vazquez, Adriana, Taskinen, Marja-Riitta, Prat, Annik, Seidah, Nabil G., Pajukanta, Päivi, Engert, James C., and Genest, Jacques

Abstract

A low level of plasma high-density lipoprotein cholesterol (HDL-C) is a risk factor for cardiovascular disease. HDL particles are modulated by a variety of lipases, including endothelial lipase, a phospholipase present on vascular endothelial cells. The proprotein convertase subtilisin/kexin type 5(PCSK5) gene product is known to directly inactivate endothelial lipase and indirectly cleave and activate angiopoetin-like protein 3, a natural inhibitor of endothelial lipase. We therefore investigated the effect of human PCSK5genetic variants on plasma HDL-C levels.

Published
2009
Full Text
View/download PDF

50. Loss of Protocadherin-12 Leads to Diencephalic-Mesencephalic Junction Dysplasia Syndrome.

Author

Guemez-Gamboa A, Çağlayan AO, Stanley V, Gregor A, Zaki MS, Saleem SN, Musaev D, McEvoy-Venneri J, Belandres D, Akizu N, Silhavy JL, Schroth J, Rosti RO, Copeland B, Lewis SM, Fang R, Issa MY, Per H, Gumus H, Bayram AK, Kumandas S, Akgumus GT, Erson-Omay EZ, Yasuno K, Bilguvar K, Heimer G, Pillar N, Shomron N, Weissglas-Volkov D, Porat Y, Einhorn Y, Gabriel S, Ben-Zeev B, Gunel M, and Gleeson JG

Subjects
Child, Child, Preschool, Female, Humans, Infant, Infant, Newborn, Male, Mutation, Protocadherins, Brain Stem abnormalities, Cadherins genetics, Nervous System Malformations genetics, Nervous System Malformations pathology
Abstract

Objective: To identify causes of the autosomal-recessive malformation, diencephalic-mesencephalic junction dysplasia (DMJD) syndrome., Methods: Eight families with DMJD were studied by whole-exome or targeted sequencing, with detailed clinical and radiological characterization. Patient-derived induced pluripotent stem cells were derived into neural precursor and endothelial cells to study gene expression., Results: All patients showed biallelic mutations in the nonclustered protocadherin-12 (PCDH12) gene. The characteristic clinical presentation included progressive microcephaly, craniofacial dysmorphism, psychomotor disability, epilepsy, and axial hypotonia with variable appendicular spasticity. Brain imaging showed brainstem malformations and with frequent thinned corpus callosum with punctate brain calcifications, reflecting expression of PCDH12 in neural and endothelial cells. These cells showed lack of PCDH12 expression and impaired neurite outgrowth., Interpretation: DMJD patients have biallelic mutations in PCDH12 and lack of protein expression. These patients present with characteristic microcephaly and abnormalities of white matter tracts. Such pathogenic variants predict a poor outcome as a result of brainstem malformation and evidence of white matter tract defects, and should be added to the phenotypic spectrum associated with PCDH12-related conditions. Ann Neurol 2018;84:646-655., (© 2018 American Neurological Association.)

Published
2018
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results