Projects Archive - Foundation for Prader-Willi Research | Genetics and Imprinting

Under the guidance of our Scientific Advisory Board through a carefully managed grants process, FPWR selects research projects based on the collaborative input of researchers and parents, choosing projects that are both scientifically meritorious and highly relevant for individuals with PWS and their families.

Search Projects

Filter projects

The molecular mechanism of SNORD116 action (year 2)

Funded Year: 2018

SNORD116 is a C/D box small nucleolar RNA that is critical for the etiology of PWS, as microdeletions encompassing only SNORD116 cause a PWS-like phenotype. The molecular functions of SNORD116 have been elusive, preventing therapy design. We showed that SNORD116 is not a typical snoRNA, as it associates with different proteins and has a different false

A transcriptome-wide approach to identifying RNA targets of the Prader-Willi locus snoRNAs (year 2)

Funded Year: 2018

Prader-Willi syndrome (PWS) traits are genetically determined by the loss of expression of genes from the paternally inherited small region located on chromosome 15. These genes are transcribed to brain-specific small nucleolar RNAs (snoRNAs) whose function is still unknown. snoRNAs were traditionally assigned a role in ribosomal RNA processing false

Consequences of targeted SNORD116 deletion in human and mouse neurons

Funded Year: 2018

The role of the brain in controlling food intake is increasingly apparent, with studies finding that genes related to obesity often play a role in brain regions crucial for feeding, appetite, and satiety. Prader-Willi syndrome, one of the most common forms of genetic obesity, results increased food intake (hyperphagia) leading to severe obesity, false

CRISPR-mediated 3D modeling, molecular dissection and epigenetic profiling of PWS

Funded Year: 2017

Deletions on chromosome 15 in the bands labeled 15q11.2-q13 on the chromosome inherited from a subject’s father cause Prader-Willi syndrome (PWS). The unique nature of this causative genetic event has been known for many years, but the precise manner in which it causes the developmental abnormalities of PWS is not completely understood since the false

The SNORD116-NHLH2 pathway: insights into the molecular genetic basis of Prader-Willi Syndrome

Funded Year: 2017

Prader-Willi Syndrome (PWS) is a genetic condition resulting from paternal inheritance of a deletion within an imprinted region of chromosome 15q. The smallest known deleted region encompasses a small nucleolar non-coding RNA locus called SNORD116 (SNORD116), but very little is known about how deletion of SNORD116 leads to PWS. As shown using false

Evaluating factors that may affect the efficacy of intranasal oxytocin treatment in PWS

Funded Year: 2017

Recent studies with oxytocin treatment in PWS have yielded inconsistent results. Intranasal administration of oxytocin by the Toulouse group decreased disruptive behaviors in patients with PWS, but a recent randomized trial in Australia of adolescents and adults of intranasal oxytocin (IN-OT) found no effect on syndrome-specific behavior in false

Gene Expression Analysis in PWS Subject Derived Dental Pulp Stem Cell Neurons (year 2)

Funded Year: 2017

There are two goals to this study: 1) To identify differences between individuals with PWS with autism from those who have PWS without autism using technology that analyzes how genes are expressed and 2) To identify a new role for SNORD115 and SNORD116 which may help explain the PWS condition or how other very small molecules that do not make false

Prevalence and aetiology of PWS low level mosaicism in UPD undetected by standard testing

Funded Year: 2017

Prader-Willi syndrome (PWS) is a severe neurodevelopmental disorder found in ~1 in 15,000 to 20,000 births. PWS phenotype caused by the loss of function of several genes located on chromosome 15. These genes are usually ‘switched on’ on the chromosome 15 that is inherited from the father and ‘switched off’ on the chromosome 15 inherited from the false

Recapitulating obesity and hyperphagia in novel adult-onset mouse models of Snord116 deletion

Funded Year: 2016

Although it is well established that deletion of SNORD116 contributes to PWS in humans, mice missing Snord116 don’t display hyperphagia and obesity. This makes it very difficult to study the biology of SNORD116 and test anti-obesity drugs. In a major breakthrough, Dr. Yeo’s group has shown that if Snord116 is deleted in adult mice, a percentage of false

The molecular mechanism of SNORD116 action and possible SNORD116 substitution strategies

Funded Year: 2016

The loss of two snoRNAs, SNORD115 and SNORD116, plays a central role in the development of Prader-Willi syndrome. However, the normal function of SNORD116 is still unclear, making it difficult to understand what goes wrong when SNORD116 is lost. Dr. Stamm’s group is exploring how SNORD116 influences other genes, and their preliminary studies false

Preclinical studies of a novel epigenetic therapy for Prader-Willi syndrome

Funded Year: 2016

Despite the significant progress in understanding the molecular basis underlying Prader-Willi syndrome, little advance has been achieved in developing the treatment specifically targeting to the molecular defect. The SNORD116 between the SNRPN and UBE3A genes is important for the major features of PWS. The host transcripts and SNORD116 in the false

Reactivation of the PWS locus via disruption of the ZNF274 silencing complex (year 2)

Funded Year: 2016

Through a normal biological process called genomic imprinting, the chromosome 15 that is inherited from the father has a set of genes that are switched on while the same set of genes on the chromosome 15 inherited from the mother are switched off. In Prader-Willi syndrome (PWS), there is no normal copy of the paternal chromosome 15 so patients false

The role of SNORD116 in the neuroendocrine phenotypes of Prader-Willi syndrome

Funded Year: 2016

A hallmark symptom of PWS is extreme, unrelenting hyperphagia associated with obesity. Other medical characteristics of individuals with PWS include low circulating growth hormone, short stature, adrenal insufficiency, hypothyroidism, and hypogonadism. Additionally, individuals with PWS have decreased levels of circulating fasting insulin compared false

Methylation test validation for combined Prader-Willi and Fragile X syndrome newborn screening

Funded Year: 2015

Activation of silenced genes in Prader-Willi syndrome

Funded Year: 2015

The genetic causes of Prader-Willi syndrome (PWS) are known, including as a complex disorder involving imprinted genes that normally only function after inheritance from the father. A dozen genes contribute to the clinical problems in PWS, although what most of these genes do is poorly understood. Additionally, although numerous mouse models that false

RNA targets of SNORD116

Funded Year: 2015

Current evidence suggests that most Prader-Willi syndrome (PWS) traits result from loss of paternally inherited SNORD116 gene group. SNORD116 belong to a class of small nucleolar RNAs (snoRNAs), which are involved in modification of other RNA species. snoRNAs act as guides to define sites of target RNA modification by partner enzymes. Typically, a false

Gene Expression Analysis in PWS Subject Derived Dental Pulp Stem Cell Neurons

Funded Year: 2015

There are two goals to this study: 1) To identify differences among individuals with PWS and autism from those who have PWS without autism by analyzing gene expression and 2) To identify new patterns of gene expression which may help explain the PWS condition or how other very small molecules that do not make protein (non-coding RNAs) implicated false

Rapamycin treatment to correct the circadian mTOR imbalance in the Snord116 deletion mouse model of PWS

Funded Year: 2015

Prader-Willi syndrome (PWS) is a neurodevelopmental disorder with a known genetic etiology, but a complex epigenetic basis.  PWS is an imprinted disorder, meaning that the genes implicated in PWS are expressed only on the paternal but not the maternal chromosome 15q11-13. At the heart of the minimally deleted region in PWS are several processed false

Biological and molecular functions of PWS-encoded small nucleolar RNA genes

Funded Year: 2015

For several decades the most extensively studied human DNA sequences were those generating messenger RNAs (mRNAs) which are used as templates for protein synthesis. The process decoding the genetic information from mRNAs to proteins is carried out by molecular machines named ribosomes and proteins are commonly perceived as essential molecules false

Reactivation of the PWS locus via disruption of the ZNF274 silencing complex

Funded Year: 2015

Through a normal biological process called genomic imprinting, the chromosome 15 that is inherited from the father has a set of genes that are switched on while the same set of genes on the chromosome 15 inherited from the mother are switched off. In Prader-Willi syndrome (PWS), there is no normal copy of the paternal chromosome 15 so patients false

Small molecules and therapeutic potential for PWS

Funded Year: 2014

A publication resulting from this project was highlighted in an FPWR Research Blog post “Promising First Steps Towards Genetic Therapy for Prader-Willi Syndrome” (December 2016)

The role of SNORD116 in Prader-Willi syndrome (year 2)

Funded Year: 2014

Prader-Willi syndrome (PWS) is caused by a loss of genes normally expressed only from the paternal chromosome 15. About 70% of PWS cases arise from Type 1 and Type 2 deletions, which are about 5 million DNA base pairs in size. Genetic mapping data from unique patients harboring smaller deletions, “microdeletions”, in the PWS region implicate the false

Genome-wide survey of DNA methylation in PWS

Funded Year: 2014

Prader-Willi syndrome (PWS) is a rare genomic imprinting disorder caused by an abnormality in the PWS critical region (PWSCR), a particular region of 15th chromosome (15q11-q13). Genomic imprinting refers to a phenomenon in which genes from specific parent can be expressed. PWSCR contains several imprinted genes that are only expressed from either false

Injectable protein gene activation therapy for PWS (year 2)

Funded Year: 2014

This proposal will investigate the development of a gene therapy for Prader-Willi syndrome (PWS). PWS is caused by the loss of a region of human chromosome 15q11-13. Humans have two copies of chromosome 15, one the mother (maternal) and one from the father (paternal). Due to an unusual mechanism called genetic imprinting, the genes affecting PWS false

The role of SNORD116 in Prader-Willi syndrome

Funded Year: 2013

Prader-Willi syndrome (PWS) is caused by a loss of genes normally expressed only from the paternal chromosome 15. About 70% of PWS cases arise from Type 1 and Type 2 deletions, which are about 5 million DNA base pairs in size. Genetic mapping data from unique patients harboring smaller deletions, “microdeletions”, in the PWS region implicate the false

Functional Assessment of snoRNA derived microRNAs in Prader-Willi Syndrome

Funded Year: 2013

Prader-Willi Syndrome (PWS) is a neurodevelopmental disorder, predominantly caused by a deletion on the long arm of chromosome 15. This deletion eliminates a group of genes called HBII-85 whose function is currently unknown. Therefore, this proposal aims to investigate the underlaying molecular mechanisms behind the loss of HBII-85 and how this false

Allele specific regulation of SNORD116 in PWS

Funded Year: 2013

Prader-Willi Syndrome (PWS), a complex genetic disorder that results from a failure to inherit a normal copy of the father’s chromosome 15. Key genes on the paternal chromosome are deleted, but how the deletion of this region leads to PWS is a complete mystery. In PWS, a normal copy of the mother’s chromosome 15 is inherited, but the genes are false

Reactivation of maternally-silenced genes in PWS

Funded Year: 2013

This proposal will investigate the development of a gene therapy for Prader-Willi syndrome (PWS). PWS is caused by the loss of a region of human cromosome 15q11-13. Humans have two copies of chromosome 15, one the mother (maternal) and one from the father (paternal). Due to an unusual mechanism called genetic imprinting, the genes affecting PWS false

Small molecular screening and therapeutic potential for PWS

Funded Year: 2013

Like most genetic disorders, there is no specific therapeutic intervention targeted to the molecular defect for Prader-Willi syndrome (PWS). The clinical presentations of PWS are caused by paternal deficiency of genes in the chromosome 15q11-q13 region. Recent reports indicate a region between the SNRPN and UBE3A genes harboring SnoRNA clusters is false

Role of SNORD116/HBII-85 snoRNAs in Prader-Willi syndrome

Funded Year: 2011

Although the genetic region on chromosome 15 that is responsible for Prader-Willi Syndrome (PWS) has been known for many years, how the gene or genes within this large region cause the complex clinical features of PWS is still unknown. We have identified a small deletion on chromosome 15 of a patient with PWS features that narrows the causative false

A Prader-Willi syndrome mouse model with brain specific ablation of snoRNA clusters from the Snrpn to Ube3a region

Funded Year: 2011

Two lines of evidence are promoted this proposal. First, recently, smaller microdeletions in the region between the human SNRPN and UBE3A genes have been reported in several cases with features consistent with PWS, including childhood obesity, hyperphagia, and hypogonadism. Second, interestingly, recent studies of genomewide survey of imprinting false

Mechanism of hyperphagia and therapeutic interventions in mouse models for Prader-Willi syndrome

Funded Year: 2011

The overall goals of our research are to elucidate the pathophysiologic pathways that lead to the metabolic and behavioral changes in PWS, and to evaluate two types of treatments for persistent hunger and food seeking behavior. We have focused on the role of a special type of RNA, called Snord116 (formally PWCR1/HBII-85) small nucleolar RNA false

R-loop formation and chromatin decondensation at the PWS critical locus

Funded Year: 2011

Prader-Willi syndrome (PWS) is a neurodevelopmental disorder with a known genetic etiology but a complex epigenetic basis. PWS is an imprinted disorder, meaning that genes expressed only on the paternal but not the maternal chromosome 15 are responsible. Furthermore, unlike genetic mutations that affect protein-coding genes, the smallest genetic false

Derivation of live Prader-Willi syndrome neurons from induced pluripotent stem (iPS) cells

Funded Year: 2010

A better understanding of the causes of Prader-Willi syndrome (PWS) and the discovery of potential therapies has been hampered by the unavailability of live tissues. In our laboratory (Marc Lalande), we have established induced pluripotent stem cell (iPSC) technology to create models of human disease in a test tube/tissue culture dish. Skin cells false

Identification of substances that substitute for the loss of snoRNAs from the Prader-Willi critical region

Funded Year: 2009

Genetic studies strongly indicate that the Prader-Willi syndrome is caused by the loss of small nucleolar RNAs (snoRNA). SnoRNAs are short RNAs that do not encode a protein. In most cases studied, snoRNAs help in the modification of other RNAs. However, the function of the snoRNAs missing in people with Prader-Willi syndrome is not clear. In false

Role of the HBII-85 snoRNA cluster in the pathogenesis of PWS

Funded Year: 2009

It has been known for many years that loss of function of the copy of the DNA inherited from the father for genes in the Prader-Willi syndrome (PWS) region cause PWS. However, there are multiple genes in the region, and it has not been clear as to exactly which gene or genes cause PWS. Based on studies of a series of rare families with false

R Loop structures maintain epigenetic imprints at the Prader-Willi Imprinting Center (year 2)

Funded Year: 2009

At the genetic level, Prader-Willi syndrome (PWS) is due to the lack of expression of a specific portion of chromosome 15. This portion contains genes that, in normal circumstances, are only active on the paternally inherited chromosome. Indeed, the corresponding genes on the maternally inherited chromosome are silenced – a phenomenon called false

Regulation of expression of Prader-Willi syndrome region genes in the hypothalamus by nutritional and hormonal signals

Funded Year: 2009

The cause of the severe obesity characteristic of patients with Prader-Willi syndrome (PWS) is unknown. In the past few years however, there has been an explosion of information regarding the factors involved in the control of bodyweight. In particular, the hormone leptin, which is produced by fat, and a group of molecules in the brain called the false

snoRNAs located in the PWS critical region regulate alternative splicing of pre-mRNAs

Funded Year: 2009

Prader Willi syndrome is caused by the loss of gene expression from a known region in the human genome. In almost all genetic diseases studied, the loss of gene expression results in a loss of a certain protein, since ultimately proteins are made from genes. One problem in understanding the Prader-Willi syndrome is that only a few proteins are false

Role of PWCR1 snoRNAs in Prader-Willi Syndrome

Funded Year: 2009

The overall goals of our research are to elucidate the genetic and pathophysiologic pathways that lead to the metabolic and behavioral changes in PWS. We have focused on the role of a special type of RNA, called PWCR1/HBII85 small nucleolar RNA (snoRNA), that was discovered in our laboratory. Studies of rare cases of PWS with smaller deletions and false

PWS mouse model with deleted snoRNA cluster

Funded Year: 2009

The overall goals of our research are to elucidate the genetic and pathophysiologic pathways that lead to the metabolic and behavioral changes in PWS. We believe that a detailed level of understanding is necessary to design rational interventions. Recently, our laboratory has focused on the role of a special type of RNA, called PWCR1/HBII-85 small false

Exploring the potential of using demethylation drugs to treat PWS

Funded Year: 2009

More than 95% of Prader-Willi syndrome (PWS) cases are caused by either a large deletion of paternal chromosome 15q11-q13 or maternal uniparental disomy (UPD) of chromosome 15. The major gene or genes responsible for PWS are subject to genomic imprinting and exclusively expressed from paternal chromosome. For patients with a large chromosomal false

Activation of the maternal allele at the PWS/AS domain as a potential therapeutic approach (year 1)

Funded Year: 2009

Prader-Willi syndrome (PWS) results from inactivation of a domain on the paternal chromosome 15 while the same domain on chromosome 15 that is of maternal origin is normally inactivated. This situation in Prader-Willi patients is therefore associated with complete silencing of a relatively large number of genes that are located in this domain. false

R-Loop structures maintain epigenetic imprints at the Prader-Willi imprinting center

Funded Year: 2009

At the genetic level, Prader-Willi syndrome (PWS) is due to the lack of expression of a specific portion of chromosome 15. This portion contains genes that, in normal circumstances, are only active on the paternally inherited chromosome. Indeed, the corresponding genes on the maternally inherited chromosome are silenced – a phenomenon called false

Activation of the maternal allele at the PWS/AS domain (Year 2)

Funded Year: 2009

Prader-Willi syndrome (PWS) results from inactivation of a domain on the paternal chromosome 15 while the same domain on chromosome 15 that is of maternal origin is normally inactivated. This situation in Prader-Willi patients is therefore associated with complete silencing of a relatively large number of genes that are located in this domain. false

donate to FPWR for PWS research