A5025191891- dental development and anomalies
- Wnt/β-catenin signaling in development and cancer
- Skin and Cellular Biology Research
- Epigenetics and DNA Methylation
- Genetic and Kidney Cyst Diseases
- Hypothalamic control of reproductive hormones
- Neuropeptides and Animal Physiology
- Asthma and respiratory diseases
- Hedgehog Signaling Pathway Studies
- Neuroendocrine Tumor Research Advances
- Genomics and Chromatin Dynamics
- Fetal and Pediatric Neurological Disorders
- Genetics and Neurodevelopmental Disorders
- Reproductive System and Pregnancy
- Regulation of Appetite and Obesity
- Genetic Syndromes and Imprinting
- Pregnancy and preeclampsia studies
- Mast cells and histamine
- Cancer-related gene regulation
- Pregnancy and Medication Impact
- CRISPR and Genetic Engineering
- Prenatal Screening and Diagnostics
- Congenital heart defects research
- Advanced Statistical Process Monitoring
- Hair Growth and Disorders
Folkhälsans Forskningscentrum
2007-2024
University of Helsinki
2010-2024
Institute of Genetics
2013
Greenwood Genetic Center
1997
Wayne State University
1997
Technion – Israel Institute of Technology
1994
Mouse Tabby ( Ta ) and X chromosome-linked human EDA share the features of hypoplastic hair, teeth, eccrine sweat glands. We have cloned gene find it to be homologous gene. The is altered in two alleles with a point mutation or deletion. expressed developing teeth epidermis; no expression seen corresponding tissues from mice. genes both encode alternatively spliced forms; novel exons now extend 3′ end All transcripts recovered same 5′ exon. longest cDNA encodes 391-residue transmembrane...
Anhidrotic ectodermal dysplasia (EDA) is an X-linked recessive disorder which affects structures. A cDNA encoding a 135 amino acid protein with mutations in 5–10% of EDA patients has been reported. We have built up complete splicing map the gene and characterized longest what most probably represents full-length transcript, EDA-A. It encodes 391 transmembrane short collagenous domain, (Gly-X-Y) 19 , highly homologous to mutated Tabby mice (Ta-A). Four new transcripts that code for truncated...
Double homeobox 4 (DUX4) is expressed at the early pre-implantation stage in human embryos. Here we show that induced DUX4 expression substantially alters chromatin accessibility of non-coding DNA and activates thousands newly identified transcribed enhancer-like regions, preferentially located within ERVL-MaLR repeat elements. CRISPR activation enhancers by C-terminal motifs results increased target embryonic genome (EGA) genes ZSCAN4 KHDC1P1. We markedly enriched zygotes, followed intense...
Anhidrotic ectodermal dysplasia (EDA) is a human genetic disorder of impaired appendage development. The EDA gene encodes isoforms novel transmembrane protein, ectodysplasin. sequence the longest isoform includes an interrupted collagenous domain 19 Gly-X-Y repeats and motif conserved in tumor necrosis factor (TNF)-related ligand family. In order to understand better function ectodysplasin protein molecule its domains, we have studied processing localization wild-type mutated transfected...
Primary cilia emanate from most human cell types, including neurons. Cilia are important for communicating with the cell's immediate environment: signal reception and transduction to/from ciliated cell. Deregulation of ciliary signaling can lead to ciliopathies certain neurodevelopmental disorders. In developing brain play well-documented roles expansion neural progenitor pool, while information about during post-mitotic neuron differentiation maturation is scarce.
Abstract Distinctive colour patterns in dogs are an integral component of canine diversity. Colour pattern differences thought to have arisen from mutation and artificial selection during after domestication wolves but important gaps remain understanding how these evolved genetically controlled. In other mammals, variation at the ASIP gene controls both temporal spatial distribution yellow black pigments. Here, we identify independent regulatory modules for ventral hair cycle expression,...
BackgroundFetal immune tolerance is crucial for pregnancy success. We studied the link between preeclampsia, a severe disorder with uncertain pathogenesis, and fetal human leukocyte antigen G (HLA-G) other genes regulating maternal responses.MethodsWe assessed sex ratios regulatory HLA-G haplotypes in population cohorts series of preeclampsia stillbirth. placental mRNA expression 136 by sequencing interferon alpha (IFNα) protein immunohistochemistry.FindingsWe found underrepresentation males...
Abstract Background Dilated cardiomyopathy (DCM) is a life-threatening heart disease and common cause of failure due to systolic dysfunction subsequent left or biventricular dilatation. A significant number cases have genetic etiology; however, as complex disease, the exact risk factors are largely unknown, many patients remain without molecular diagnosis. Methods We performed GWAS followed by whole-genome, transcriptome, immunohistochemical analyses in spontaneously occurring canine model...
Anhidrotic ectodermal dysplasia (EDA) is characterized by defects in the development of teeth, hair, and sweat glands. To study expression human gene defective EDA fetal (Weeks 6–23 gestational age) adult tissues, situ hybridization immunohistochemistry were used. First signs detected at Week 8 epidermis neuroectodermal cells. Starting 12, osteoblasts thymus positive for mRNA. Hair follicles expressed mRNA from 18 weeks. The presence protein coincided with tissues examined. pattern...
DNA methylation is a hallmark of genomic imprinting and differentially methylated regions (DMRs) are found near in imprinted genes. Imprinted genes expressed only from the maternal or paternal allele their normal balance can be disrupted by uniparental disomy (UPD), inheritance both chromosomes chromosome pair exclusively either mother father. Maternal UPD for 7 (matUPD7) results Silver-Russell syndrome (SRS) with typical features growth retardation, but no gene has been conclusively...
Retinoid acid receptor-related Orphan Receptor Alpha (RORA) was recently identified as a susceptibility gene for asthma in genome-wide association study. To investigate the impact of RORA on susceptibility, we performed genetic study between single nucleotide polymorphisms (SNPs) vicinity asthma-associated SNP (rs11071559) and asthma-related traits. Because regulatory region previously implicated gene, Neuropeptide S receptor 1 (NPSR1), has predicted elements binding, hypothesized that may...
The dog, Canis lupus familiaris, is an important model for studying human diseases. Unlike many organisms, the dog genome has a comparatively poor functional annotation, which hampers gene discovery development, morphology, disease, and behavior. To fill this gap, we established comprehensive tissue biobank both wolf samples. consists of 5485 samples representing 132 tissues from 13 dogs, 12 embryos, 24 wolves. In subset 100 nine dogs characterized expression activity each promoter,...
Neuroendocrine tumors (NETs) arise from disseminated neuroendocrine cells and express general specific markers. Neuropeptide S receptor 1 (NPSR1) is expressed in its ligand neuropeptide (NPS) affects cell proliferation. Our aim was to study whether NPS/NPSR1 could be used as a biomarker for neoplasms identify the gene pathways affected by NPS/NPSR1. We collected cohort of NETs comprised 91 samples endocrine glands, digestive tract, skin, lung. Tumor type validated immunostaining...
Cystatin B (CSTB) acts as an inhibitor of cysteine proteases the cathepsin family and loss-of-function mutations result in human brain diseases with a genotype-phenotype correlation. In most severe case, CSTB-deficiency disrupts development, yet molecular basis this mechanism is missing. Here, we establish CSTB regulator chromatin structure during neural stem cell renewal differentiation. Murine precursor cells (NPCs) undergo transient proteolytic cleavage N-terminal histone H3 tail by...
Here, we present a modification of single-cell tagged reverse transcription protocol to study gene expression on level or with limited RNA input. We describe different enzymes for and cDNA amplification, modified lysis buffer, additional clean-up steps before amplification. also detail an optimized sequencing method handpicked single cells, tens hundreds as input material mammalian preimplantation development. For complete details the use execution this protocol, please refer Ezer et al.1
Single nucleotide polymorphisms (SNPs) close to the gain-of-function substitution, Asn(107)Ile (rs324981, A>T), in Neuropeptide S Receptor 1 (NPSR1) have been associated with asthma. Furthermore, a functional SNP (rs4751440, G>C) (NPS) encodes Val(6)Leu substitution on mature peptide that results reduced bioactivity. We sought examine effects of different combinations these NPS and NPSR1 variants downstream signaling genetic risk In transfected cells, magnitude NPSR1-induced activation...
We have developed a protocol for barcoded cDNA libraries of 48 samples to study gene expression across tissues in the domestic dog, Canis familiaris, by modifying Single-Cell Tagged Reverse Transcription (STRT) (Islam et al., 2012, 2014). The reads represent mRNA 5′ ends, enabling transcription start sites (TSS). Our modifications include longer UMIs molecular counting and Globin-Lock® deplete globin mRNAs that are abundant blood blood-rich dominating all reads.
Anhidrotic ectodermal dysplasia (EDA) is a rare X-linked recessive disorder characterized by the absence or hypoplasia of hair, teeth and sweat glands. The gene responsible for has recently been cloned. predicted product 135 amino acid protein with no significant homology to previously known proteins. As first step analyze function, we have studied subcellular localization EDA expressed in two epithelial cell lines, COS-1 MCF-7. Biochemical fractionation confocal imaging analysis show that,...
Many human cell types are ciliated, including neural progenitors and differentiated neurons. Ciliopathies characterized by defective cilia comprise various disease states, brain phenotypes, where the underlying biological pathways largely unknown. Our understanding of neuronal is rudimentary, an easy-to-maintain, ciliated model absent. The Lund mesencephalic (LUHMES) line a derived from fetal mesencephalon. LUHMES cells can easily be maintained into mature, functional neurons within one...
In oocyte to embryo transition, the fertilized undergoes final maturation and genome is gradually activated during first three cell divisions. How this transition coordinated which factors drive processes in humans largely unknown. Here we studied role of double homeodomain transcription factor DUX4 regulating human transition. knockdown zygotes show delayed transcriptome reprogramming days after fertilization. Our combined experimental approaches allowed integrated analysis on...
The pathogenesis of type 1 diabetes (T1D) is associated with genetic predisposition and immunological changes during presymptomatic disease. Differences in immune cell subset numbers phenotypes between T1D patients healthy controls have been described; however, the role function these still unclear. Here we aimed to analyze transcriptomic landscapes peripheral blood mononuclear cells (PBMCs) disease.Transcriptomic differences PBMCs were compared cases positive for islet autoantibodies...
Neuroendocrine tumors (NETs) are often diagnosed from the metastases of an unknown primary tumor. Specific immunohistochemical (IHC) markers indicating location a tumor needed. The proprotein convertase subtilisin/kexin type 2 (PCSK2) is found in normal neural and neuroendocrine cells, known to express NETs. We investigated tissue microarray (TMA) 86 13 different organs 9 metastatic NETs, including tumor‐metastasis pairs, for PCSK2 expression with polymer‐based IHC. was strongly positive all...